peptidefix

Clinical Research

Published studies on the peptides we cover. Each is labelled by study type so you can see at a glance whether a finding comes from cells, animals or people.

Evidence map

Every peptide and the research on peptidefix behind it, one square per paper. Pick a peptide to see its papers.

humananimalcellreview or preprint
161 papers

BPC-157 and the gut–brain axis: emerging links between cytoprotection and neuroregeneration

Pietrzyk B, Waluga M (2026). Annales Academiae Medicae Silesiensis. doi:10.18794/aams/216086

A PRISMA-style systematic review of BPC-157 literature from 2000 to mid-2025, screening 630 records down to 64 studies (52 preclinical, 12 early human or observational reports) with a focus on the gut-brain axis. The authors report that in animal models BPC-157 is described as cytoprotective and anti-inflammatory, with effects on neuronal survival, angiogenesis and several neurotransmitter systems, and that the human data are limited to small safety-oriented reports. They note the preclinical evidence is small in volume and heterogeneous in quality and call for controlled clinical trials.

review n/a (systematic review of 64 studies: 52 preclinical, 12 early human or observational)
BPC-157

Middle-aged mice treated with GHK-Cu peptide administered intraperitoneally or intranasally show behavioral rescue but divergent hippocampal aging programs

Mazzola J, Rosenfeld M, Tucker M, Wezeman J, Ladiges W, Liao GY (2026). bioRxiv (preprint). doi:10.64898/2026.04.09.717524

A preprint comparing two ways of giving GHK-Cu to aged mice: a short intraperitoneal course and a longer intranasal course. Spatial learning was assessed with a navigation task and the hippocampus was examined by immunohistochemistry and RNA sequencing. The intranasal course was associated with better escape learning in both sexes, while the intraperitoneal course produced only a transient effect in males. Gene-expression changes differed sharply between the two routes. The authors conclude that route and duration shape the response. Not yet peer reviewed.

preprint (not peer-reviewed) aged C57BL/6J mice (20–21 months), both sexes
GHK-Cu

Cagrilintide and retatrutide combination therapy enhances weight loss and metabolic outcomes in obese male rats

Petersen J, Merrild C, Holm SK, et al. (2026). Nature Metabolism. doi:10.1038/s42255-026-01603-y

Tested daily co-administration of retatrutide (a GLP-1/GIP/glucagon receptor tri-agonist) and cagrilintide (an amylin/calcitonin receptor co-agonist) in diet-induced obese male rats, against each drug alone and against matched combinations built on semaglutide or tirzepatide. The combination reduced body weight and food intake more than the comparators and improved circulating cholesterol, triglycerides and insulin. Pair-feeding and weight-matching experiments indicated the extra weight loss was not explained by reduced intake alone; plasma proteomics and brain transcriptomics were used to characterise the response. A rat study; several authors are co-founders of obesity-drug companies.

animal diet-induced obese male rats
RetatrutideCagrilintide

FOXO4-DRI regulates endothelial cell senescence via the P53 signaling pathway

Hu Z, Li F, Hu C, et al. (2026). Frontiers in Bioengineering and Biotechnology. doi:10.3389/fbioe.2025.1729166

Looked at FOXO4-DRI in blood-vessel ageing. Injection into naturally aged and progeroid mice was associated with reduced markers of aortic ageing and improved aortic function. In cultured endothelial cells made senescent by oxygen-glucose deprivation, the peptide reduced senescence and improved cell function; co-immunoprecipitation experiments indicated it blocks FOXO4 binding to p53, leading to p53 nuclear export and caspase-3-mediated apoptosis of senescent cells. A mouse and cell study.

animal naturally aged and progeroid mice; cultured endothelial cells under oxygen-glucose deprivation
FOXO4-DRI

NAD+ supplementation for anti-aging and wellness: A PRISMA-guided systematic review of preclinical and clinical evidence

Gallagher C, Emmanuel OO (2026). Ageing Research Reviews. doi:10.1016/j.arr.2026.103057

Reviewing 113 studies, the authors report that in rodents NAD+ augmentation was often associated with metabolic, mitochondrial and inflammatory improvements, varying by model. In humans, oral precursors nicotinamide riboside and nicotinamide mononucleotide reliably raised NAD-related metabolites in blood or cells and were generally well tolerated over weeks to months, but effects on function, metabolism and other healthspan outcomes were mixed and often null. Their key finding for this page: no eligible outcomes trial evaluated intravenous or intramuscular NAD+ itself for anti-ageing or wellness. The evidence base is for precursors taken by mouth, not for NAD+ given by infusion.

review n/a (113 studies: 33 human intervention studies, 28 of them randomised, and 80 rodent studies, 2010 to 2025)
NAD+

Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial

Bajaj HS, Welch M, Shah P, et al. (2026). The Lancet. doi:10.1016/S0140-6736(26)00967-0

A 40-week phase 3 trial (TRANSCEND-T2D-1) of retatrutide, a GIP, GLP-1 and glucagon receptor agonist, used on its own in adults with type 2 diabetes not controlled by diet and exercise. 537 participants were randomised to one of three retatrutide dose levels or placebo. The primary endpoint was change in HbA1c: it fell by 1.69 to 1.94 percentage points across the retatrutide groups against 0.81 with placebo. Mean body weight changed by -11.5% to -15.3% with retatrutide against -2.6% with placebo. The most common adverse events were gastrointestinal, mostly mild to moderate; 2 to 5% of retatrutide participants stopped treatment because of adverse events, against none on placebo. The trial was funded by Eli Lilly, which develops retatrutide, and six of the ten authors are Lilly employees.

human humans, n=537, phase 3 randomised double-blind placebo-controlled trial (48 sites in the USA, Mexico and India)
Retatrutide

Semaglutide and cardiovascular risk reduction: a mediation analysis of the SELECT trial

Colhoun HM, Lincoff AM, Ryan D, et al. (2026). European Heart Journal. doi:10.1093/eurheartj/ehag524

A mediation analysis of the SELECT trial, in which semaglutide reduced major cardiovascular events against placebo in adults with established cardiovascular disease and overweight or obesity, without diabetes. The authors tested how much of that reduction could be explained by two-year changes in body weight, waist circumference, hsCRP (an inflammation marker), HbA1c, lipids, blood pressure and kidney measures. Semaglutide improved all of them. Waist circumference and hsCRP had the largest point estimates, but every estimate had wide confidence intervals, and supplementary analyses suggested the body weight and waist estimates were unreliable. The authors conclude the cardiovascular effect could not be attributed to known risk factors with any certainty.

human humans, n=17,604, secondary (mediation) analysis of the SELECT randomised trial
Semaglutide

Comparative Effectiveness of Once-Weekly Semaglutide Versus Sulfonylureas, DPP4 Inhibitors, and Thiazolidinediones in Patients with Type 2 Diabetes and Chronic Kidney Disease

Amamoo J, Wang Y, Liu H, et al. (2026). Advances in Therapy. doi:10.1007/s12325-026-03744-8

A retrospective study of US insurance claims comparing semaglutide injections with older oral diabetes drugs (sulfonylureas, DPP-4 inhibitors and thiazolidinediones) in adults with type 2 diabetes and chronic kidney disease. In people who could not take or had not responded well to SGLT2 inhibitors, semaglutide was associated at 12 months with larger falls in HbA1c, body weight and systolic blood pressure and a small rise in eGFR. In a second sample, semaglutide was associated with a lower risk of a combined outcome of dialysis, kidney transplant, severe loss of kidney function or death (adjusted hazard ratio 0.78). It is an observational study, so it shows associations rather than cause, and it was funded by Novo Nordisk, which makes semaglutide; five authors were Novo Nordisk employees.

human adults with type 2 diabetes and chronic kidney disease, retrospective cohort from US insurance claims (2016 to 2023), analysed in two samples
Semaglutide

Oral Semaglutide in Routine Clinical Practice: 24-Month Real-World Effectiveness, Persistence and Safety in Adults With Type 2 Diabetes

Baldassarre MPA, Di Dalmazi G, Carrieri F, et al. (2026). Diabetes, Obesity and Metabolism. doi:10.1111/dom.71371

A retrospective study of 232 adults with type 2 diabetes who started oral semaglutide at one Italian diabetes clinic, followed for 24 months. Over that time HbA1c fell by 0.8 percentage points and body weight by 5.7 kg on average; total and LDL cholesterol also fell, and kidney measures (eGFR and urine albumin) stayed stable. 44% reached a combined target of HbA1c at or below 7% with at least 5% weight loss by 24 months, and 68.5% were still on the drug at 24 months. Among those who stopped, switching to another GLP-1 receptor agonist was the most common next step. No new safety concerns were reported. As a single-centre study without a comparison group, it describes outcomes in routine care rather than testing the drug against an alternative.

human humans, n=232, retrospective single-clinic cohort (Italy), adults with type 2 diabetes
Semaglutide

Tirzepatide versus GLP-1 receptor agonists and stroke in patients with atrial fibrillation and type 2 diabetes

Lin CL, Lin KC, Yu JM, et al. (2026). Nature Communications. doi:10.1038/s41467-026-77047-5

A retrospective study using a large international network of electronic health records, comparing adults with atrial fibrillation and type 2 diabetes who started tirzepatide with matched adults who started another GLP-1 receptor agonist (14,118 pairs). Tirzepatide use was associated with lower risks of any stroke, ischaemic stroke, haemorrhagic stroke and death from any cause; at one year the absolute difference was 2.1 percentage points for stroke and 6.2 for death. The authors describe the findings as observational and say randomised trials are needed before treatment recommendations change.

human humans, 14,118 matched pairs, retrospective cohort from an international federated electronic health-record network, adults with atrial fibrillation and type 2 diabetes
Tirzepatide

SGLT2 inhibitors, semaglutide, and finerenone in diabetic kidney disease: a Bayesian network meta-analysis

He Z, Wang X, Zhang L, et al. (2026). Frontiers in Pharmacology. doi:10.3389/fphar.2026.1882227

A Bayesian network meta-analysis comparing three drug classes with phase 3 kidney and heart outcome data in type 2 diabetes with chronic kidney disease: SGLT2 inhibitors, semaglutide and finerenone. It pooled six trial datasets covering 20,521 people. All three reduced cardiovascular risk against placebo, with no significant differences between them. On kidney outcomes, SGLT2 inhibitors ranked first, semaglutide second and finerenone third; semaglutide was numerically but not significantly ahead of finerenone. The authors note that the one significant indirect difference, SGLT2 inhibitors over finerenone, depends on analysing the two finerenone trials separately and treat it as hypothesis-generating.

meta-analysis n=20,521 across six phase 3 randomised-trial datasets (CREDENCE, DAPA-CKD and EMPA-KIDNEY type 2 diabetes subgroups, FIDELIO-DKD, FIGARO-DKD, FLOW)
Semaglutide

Effects of Liraglutide and Semaglutide on Cardiometabolic Dysregulation and Oxidative Stress in an Experimental Model of Metabolic Syndrome

Ravić MP, Srejović IM, Andjić MM, et al. (2026). Medical Sciences. doi:10.3390/medsci14050590

A rat study comparing liraglutide and semaglutide with saline in male rats given a metabolic-syndrome-like condition through a high-fat diet and a low dose of streptozotocin. After six weeks of treatment the researchers measured blood pressure, glucose and lipids, heart function by ultrasound and, in isolated hearts, recovery after a period of interrupted blood flow. Both drugs improved the metabolic profile, with semaglutide having the larger effect on body weight, and both improved heart muscle recovery after the interrupted flow, lowered oxidative stress markers and reduced tissue damage seen under the microscope in the heart, liver and pancreas. These are animal results.

animal male Wistar rats with diet- and streptozotocin-induced metabolic syndrome (n not in abstract)
Semaglutide

Late-life semaglutide treatment slows ageing and extends lifespan in female mice

Feng Y, et al. (2026). Nature. doi:10.1038/s41586-026-10940-7

A study in 20-month-old female mice that were treated with semaglutide for three months. Treated mice showed better physiological function, a weaker signature of several ageing hallmarks and a longer lifespan than untreated mice. Semaglutide changed the activity of nutrient-sensing pathways and ageing-related genes. Compared directly with calorie restriction, it preserved baseline function and reproduced many of calorie restriction's effects, and was associated with improved exploratory behaviour, spatial memory and glucose control. This is an animal study; the paper does not test people. It was funded by US National Institute on Aging grants, and the authors disclose a patent application on GLP-1 receptor agonists for healthy ageing.

animal mice, 20-month-old female C57BL/6, lifespan cohort plus a 3-month cohort, with a calorie-restriction comparison group
Semaglutide

Weight loss with GLP-1 medicines does not result in a disproportionate loss of muscle mass or function in obese mice and humans

Langer HT, et al. (2026). Cell Reports Medicine. doi:10.1016/j.xcrm.2026.102665

A paper combining four preclinical studies in obese mice with a proof-of-concept clinical trial of a GLP-1 medicine in adults with obesity. In the mice, weight loss was mostly fat, with a small fall in lean mass, and muscle was relatively larger compared with body weight even though absolute muscle mass fell. In the human trial, body composition improved without a negative effect on strength. GLP-1 treatment also produced protein-level changes in muscle that differed from calorie restriction alone. The abstract does not give human sample size; the mouse and human parts are different study designs and the human trial is small.

animal four studies in obese mice plus a small proof-of-concept human trial (NCT05606471); human n to confirm from the paper
Semaglutide

BPC 157 in Rodent Ischemia-Reperfusion Injury: A Critical Review of Preclinical Evidence

Demirtaş H (2026). International Journal of Molecular Sciences. doi:10.3390/ijms27188344

A single-author critical review of preclinical rodent studies of BPC 157 in ischemia-reperfusion injury models. It examines oxidative stress, endothelial and nitric oxide responses, inflammation and cell death across organs. Reported findings include reduced oxidative injury, altered vascular responses and protective effects in skeletal muscle, intestine, liver and hippocampus models. The author notes the evidence is heterogeneous, with short observation periods and single-dose designs, and that it is hypothesis-generating rather than an established therapy. No human data are reviewed.

review n/a (review of rodent studies, literature search to 24 June 2026)
BPC-157

Semaglutide for Treating Paediatric Craniopharyngioma-Related Obesity: A Multicentre Case Series

Dornberger et al. (2026). Diabetes, Obesity and Metabolism. doi:10.1111/dom.71403

A multicentre retrospective case series of 20 adolescents with obesity related to craniopharyngioma, a brain tumour, treated off-label with semaglutide. Before treatment their BMI was rising by about 3.5 kg/m2 a year; after one year of treatment it had fallen by 2.5 kg/m2 (p<0.001), and 40% had a BMI reduction of 10% or more. Gastrointestinal side effects occurred in 30%, all mild. There were no discontinuations, pituitary decompensation or tumour recurrence. It is a small uncontrolled case series with no comparison group.

human humans, n=20, adolescents (mean age 14.0), multicentre retrospective case series
Semaglutide

GLP-1R agonist semaglutide protects human forebrain organoids from cholesterol-induced neurotoxicity

Yu et al. (2026). Alzheimer's & Dementia. doi:10.1002/alz.71888

A laboratory study using human stem-cell-derived forebrain organoids exposed to excess cholesterol, a model of lipid-driven neural injury. Semaglutide protected neural cells from the injury and was linked to activation of cAMP-PKA and PI3K/Akt-mTOR signalling, less lipid droplet build-up and less oxidative stress. Single-cell analysis suggested partial preservation of disrupted cell-to-cell signalling, including the midkine network, and calcium activity patterns were stabilised. This is a cell-model study with no animals or people. Funded by Chinese national and provincial research grants; no industry funding disclosed.

in-vitro human iPSC-derived forebrain organoids exposed to cholesterol overload
Semaglutide

Real-world effectiveness of 6-month tirzepatide therapy on body weight and composition in adults with overweight and obesity

Brancato D, et al. (2026). Journal of Diabetes and Its Complications. doi:10.1016/j.jdiacomp.2026.109419

A retrospective observational study of 122 adults with overweight or obesity (80% women, mean age 44) who received tirzepatide alongside a low-carbohydrate diet and physical activity advice at a clinic in Italy. Over 24 weeks mean body weight fell from 95 to 80 kg and BMI from 35 to 29. Fat mass fell by about 35% while skeletal muscle was preserved, and HbA1c, fasting glucose and an insulin-resistance index also improved. The authors compare the weight loss to the 72-week SURMOUNT-1 trial. There was no control group, and diet and activity changes were part of the programme. No competing interests declared.

human humans, n=122, retrospective observational study, 24 weeks
Tirzepatide

Combined Semaglutide and Sodium-Glucose Cotransporter-2 Inhibitor Use and Metabolic Outcomes in Chinese Adults With Diabetes: Post Hoc Analysis

Wang S, et al. (2026). Diabetes Therapy. doi:10.1007/s13300-026-01915-y

A post hoc analysis of the SCHOLAR real-world study in Chinese adults with diabetes, looking at the 42.3% of participants who used semaglutide together with an SGLT2 inhibitor. Mean HbA1c fell by 0.64 percentage points from baseline to month 6, and by 1.20 points in those on continuous combined treatment with a baseline HbA1c of 7% or higher. The share with HbA1c under 7% rose from 37.8% to 55.1%. Total and LDL cholesterol and triglycerides fell and HDL rose. Gastrointestinal events were the most frequent adverse events. It is a non-randomised, post hoc analysis. Funded by Novo Nordisk (China); two authors are Novo Nordisk employees.

human humans, n=11,361, post hoc analysis of the SCHOLAR real-world study, 6 months
Semaglutide

Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial

Bellido et al. (2026). The Lancet. doi:10.1016/S0140-6736(26)01861-1

A phase 3 trial of retatrutide in 1,152 adults with obesity and type 2 diabetes, randomised to one of three retatrutide dose levels or placebo for 80 weeks. Mean body weight fell by 11.9%, 16.8% and 18.8% across the three retatrutide groups against 5.1% with placebo. Gastrointestinal events were more common with retatrutide: diarrhoea in 27 to 34% against 13% on placebo, and nausea in 14 to 28% against 8%. Seven participants died during the trial and the deaths were judged unrelated to the intervention. The trial was funded by Eli Lilly, which develops retatrutide, and several authors disclose consultancy or advisory roles with drug companies. Retatrutide is investigational and not an approved medicine.

human humans, n=1,152, phase 3 randomised double-blind placebo-controlled trial, 80 weeks
Retatrutide

Potential bone marrow-driven reduction of circulating inflammatory monocytes by semaglutide in Type 2 diabetes

Teunis et al. (2026). European Heart Journal. doi:10.1093/eurheartj/ehag627

A small before-and-after study in 16 people with type 2 diabetes treated with semaglutide for six months. HbA1c fell by 21.1 mmol/mol, weight by 6.7 kg and hsCRP by 1.0 mg/L. Circulating CD16-positive monocytes, an inflammatory immune cell type, fell by 18.8%, and bone marrow retention of these cells rose in line with weight loss. Several inflammatory markers decreased, and bone marrow uptake on a DOTATATE PET scan fell by 17.5%, with no change in coronary or spleen uptake. There was no control group. Funded by Dutch and European public grants; no industry funding disclosed.

human humans, n=16, single-arm before-and-after study, 6 months, no control group
Semaglutide

Study on the Regulatory Mechanism of GLP-1 Receptor Agonist Liraglutide in Diabetic Corneal Epithelial Wound Healing

Liu et al. (2026). Investigative Ophthalmology & Visual Science. doi:10.1167/iovs.67.11.52

An experimental study of liraglutide in diabetic corneal injury, using diabetic mice and cells grown in high glucose. Liraglutide improved cell viability, proliferation and migration and reduced cell death. It activated the Nrf2/HO-1/NQO1 and PI3K/Akt pathways, lowering oxidative stress, and reduced inflammatory macrophage infiltration through lower MAPK signalling. This is an animal and cell study and does not test people. Funding is not stated in the abstract.

animal streptozotocin-induced diabetic mice plus high-glucose cell models

Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity

Jastreboff et al.; TRIUMPH-1 Investigators (2026). New England Journal of Medicine. doi:10.1056/NEJMoa2604169

The phase 3 TRIUMPH-1 trial randomised 2,339 adults with obesity to retatrutide, a GIP, GLP-1 and glucagon receptor agonist, at one of three dose levels or placebo for 80 weeks. Body weight fell by 17.6%, 23.7% and 25.0% in the retatrutide groups against 3.9% with placebo. Among 574 participants with knee osteoarthritis, pain scores improved more than on placebo, and among 243 with obstructive sleep apnoea, the apnoea-hypopnoea index fell. Gastrointestinal events were the most common adverse events. The trial was funded by Eli Lilly. Retatrutide is investigational and not an approved medicine.

human humans, n=2,339, phase 3 randomised double-blind placebo-controlled trial, 80 weeks
Retatrutide

Real-world effectiveness and safety of low-dose tirzepatide in Japanese people with type 2 diabetes: a multicenter, retrospective, single-arm, observational study (ESTATE)

Iwamoto et al.; East Shizuoka Tirzepatide study collaborators (2026). Endocrine Journal. doi:10.1507/endocrj.EJ26-0274

A multicentre retrospective observational study in Japan of 88 people with type 2 diabetes who received tirzepatide for 24 weeks. HbA1c fell by 1.5 percentage points and BMI by 1.5 kg/m2 (both p<0.001). Serum albumin rose, and alanine transaminase and LDL cholesterol fell. A higher baseline HbA1c predicted a larger HbA1c fall. Gastrointestinal symptoms were the main adverse events. The authors note that the single-arm observational design, with no control group, limits causal inference. Funding is not stated in the abstract.

human humans, n=88, multicentre retrospective single-arm observational study, 24 weeks
Tirzepatide

Survodutide Once Weekly in Adults with Obesity and Type 2 Diabetes

Wharton S, le Roux CW, Startseva E, et al. (2026). New England Journal of Medicine. doi:10.1056/NEJMoa2607219

A phase 3 trial of survodutide, a dual glucagon and GLP-1 receptor agonist, in 752 adults with type 2 diabetes and a BMI of 27 or more, randomised to one of two survodutide dose levels or placebo for 76 weeks. Mean weight fell by 8.2% and 9.8% in the two survodutide groups against 3.9% with placebo, and HbA1c fell by 0.8 to 0.9 percentage points against 0.2. Gastrointestinal adverse events occurred in 72.8 to 77.7% of survodutide participants against 38.6% on placebo, typically mild to moderate and transient. The trial was funded by Boehringer Ingelheim. Survodutide is investigational and not an approved medicine.

human humans, n=752, phase 3 multinational randomised double-blind placebo-controlled trial, 76 weeks

Nephroprotective Effects of the Dual GCGR/GLP-1R Agonist Survodutide in Hypertension-Accelerated Diabetic Kidney Disease

Hamilton A, Thisted L, Ougaard M, et al. (2026). Diabetes, Obesity and Metabolism. doi:10.1111/dom.71387

A preclinical study in db/db mice with induced, hypertension-accelerated diabetic kidney disease, comparing survodutide, a dual glucagon and GLP-1 receptor agonist, with vehicle over 10 weeks. Treated mice had lower body weight, blood glucose and urinary albumin, with less glomerulosclerosis, kidney enlargement and inflammation. Three-dimensional kidney imaging showed reduced kidney and glomerular enlargement and higher glomerular density, and liver markers were consistent with glucagon receptor activation. This is a mouse study and does not test people. Funding is not stated in the abstract.

animal mice, db/db with induced advanced diabetic kidney disease, 10 weeks of treatment against vehicle

Chronic semaglutide treatment attenuates cue-induced reinstatement of cocaine-seeking and cocaine-induced stereotypy in male and female rats

Turner CA, Morales Pagán N, Pereira D, et al. (2026). bioRxiv (preprint). doi:10.64898/2026.09.21.753157

A preprint, not yet peer-reviewed, from the University of Michigan. Rats that had self-administered cocaine received semaglutide during a 30-day abstinence period and were then tested for relapse-like behaviour. Semaglutide reduced cue-triggered reinstatement of cocaine-seeking and cocaine-induced repetitive movements in male and female rats. Lever pressing was still raised after a cocaine priming test, so the effect was partial. The authors say the results support further study. This is an animal preprint. Funding is not stated in the abstract.

preprint (not peer-reviewed) male and female rats (n not captured), preprint
Semaglutide

Former company and directors behind BioV8 to face court for alleged unlawful advertising of peptides

Therapeutic Goods Administration (Australia) (2026). Therapeutic Goods Administration. Source

On 28 September 2026 the Therapeutic Goods Administration (TGA) announced that it has started Federal Court proceedings against a former peptide-selling company, formerly BioV8 Pty Ltd and now in liquidation, and its two former directors. The TGA alleges that between 6 June 2024 and 14 July 2025 the company unlawfully advertised peptides including BPC-157, CJC-1295 and GHRP-6 on its website and social media, including claims about treating serious conditions, which are restricted representations needing TGA approval. The TGA is seeking declarations and financial penalties and says it will continue to act on unlawful advertising of peptides. The allegations have not been decided by the court.

regulatory (not peer-reviewed) Australia, TGA media release on Federal Court proceedings
BPC-157CJC-1295

Semaglutide, independent of weight loss, attenuates cardiac and hepatic remodelling in experimental heart failure with preserved ejection fraction

Elbatreek MH, et al. (2026). European Heart Journal. doi:10.1093/eurheartj/ehag732

A preclinical study in two animal models of heart failure with preserved ejection fraction, ZSF1 obese rats and Göttingen minipigs. Semaglutide improved diastolic function and reduced cardiac and liver fibrosis, in a way the authors say was independent of weight loss and linked to lower pro-fibrotic and hypertrophic signalling. This is an animal study; it does not test people. The authors note that clinical translation, and GLP-1 receptor engagement in heart tissue, need further study. Funding was from several institutional sources.

animal ZSF1 obese rats and Göttingen minipigs with induced heart failure with preserved ejection fraction
Semaglutide

Tirzepatide alleviates hepatic steatosis and inflammation in MASLD partly through suppression of macrophage Dectin-1/Syk/NF-kB signaling

He Y, Ma T, Xing H, et al. (2026). European Journal of Pharmacology. doi:10.1016/j.ejphar.2026.179418

A mouse and cell study of tirzepatide in diet-induced fatty liver disease (MASLD). Tirzepatide improved metabolic markers, liver injury and liver fat in the mice and reduced liver macrophage numbers, Dectin-1 expression and Syk/p65 phosphorylation; the authors suggest the effect works partly through that macrophage pathway. This is an animal and cell study; it does not test people. The authors declare no competing interests.

animal diet-induced male C57BL/6J mice (n not stated in abstract), plus RAW264.7 macrophage and HepG2 liver cell lines
Tirzepatide

Efficacy and Safety of Chemically Synthesized Semaglutide Injection (HD1916) for the Treatment of Obesity: A Multicenter, Randomized, Phase III Trial

Gao L, Ma Y, Zhang Q, et al. (2026). Diabetes, Obesity and Metabolism. doi:10.1111/dom.71354

A multicentre, randomised, open-label phase III trial in 462 adults with obesity and without diabetes, comparing a chemically synthesised semaglutide product (HD1916) with the reference semaglutide (Wegovy). Mean weight reduction was about 13% with HD1916 and about 14% with the reference, which the authors report as equivalent, and adverse events occurred in similar proportions in both groups. The trial was open-label.

human 462 adults aged 18-75 with obesity and without diabetes (231 per group); multicentre, randomised, open-label, active-controlled phase III equivalence trial
Semaglutide

GHK-Cu delays aging in Caenorhabditis elegans via coordinated regulation of mitochondrial function and activation of DAF-16/SKN-1 pathways

Wen H, Zhao K, Luo X, et al. (2026). Biogerontology. doi:10.1007/s10522-026-10444-x

A laboratory study in C. elegans roundworms testing GHK-Cu (the copper complex of the tripeptide GHK). GHK-Cu extended lifespan and improved several age-related measures, including stress resistance, movement and lipid accumulation. It also preserved mitochondrial function and activated the DAF-16 and SKN-1 pathways. The authors describe it as the first mechanistic evidence of this kind. The study was in worms, not people. No competing interests were declared.

animal C. elegans roundworms
GHK-Cu

Nicotinamide mononucleotide supplementation improves polycystic ovary syndrome by activating SIRT2-mediated LDHA K119 deacetylation to enhance glycolytic activity

Zhang Z, Xue H, Tu H, et al. (2026). International Journal of Biological Macromolecules. doi:10.1016/j.ijbiomac.2026.154894

A study of nicotinamide mononucleotide (NMN), a precursor of NAD+, in a rat model of polycystic ovary syndrome and in a human granulosa-like cell line. In the rats, NMN reversed insulin resistance, raised androgen levels, estrous cycle disruption and polycystic ovarian shape, and raised ovarian NAD+ and glycolytic activity. Cell experiments pointed to SIRT2-mediated deacetylation of the enzyme LDHA. The authors call it preclinical evidence. No competing interests were declared.

animal PCOS rat model; human granulosa-like KGN cells
NAD+

Body composition, hepatic fat, metabolic, and safety outcomes of tesamorelin in HIV-associated lipodystrophy: a meta-analysis of randomized controlled trials

Badran AS, Helal A, Shata KS, Ayesh H (2026). Obesity Research & Clinical Practice. doi:10.1016/j.orcp.2026.01.002

A systematic review and random-effects meta-analysis of five randomised trials of tesamorelin, a growth hormone-releasing hormone analogue, against placebo in adults with HIV-associated lipodystrophy. Tesamorelin was associated with reductions in visceral adipose tissue (mean difference -27.7 cm2), trunk fat, hepatic fat and waist circumference, and a rise in lean body mass, with no significant change in subcutaneous fat, BMI or CD4 counts. The reported adverse events included joint and muscle pain, paraesthesia and injection-site reactions. The authors rate the certainty with GRADE; no competing interests were declared.

meta-analysis 5 randomised placebo-controlled trials in adults with HIV
Tesamorelin

Protective effects of BPC 157 in rats with experimentally induced lower extremity ischemia-reperfusion injury

Yildirim AK, Demirtas H, Ozer A, Arslan M (2026). Scientific Reports. doi:10.1038/s41598-026-55449-1

A rat study of BPC 157 in lower-limb ischemia-reperfusion injury induced by aortic clamping. The injury raised markers of oxidative stress, inflammation and apoptosis and damaged muscle tissue. In rats given BPC 157, these markers were lower, antioxidant measures were restored, VEGF expression was partly restored and muscle architecture looked better. The authors say larger cohorts and dose-response work are needed. No competing interests were declared.

animal 24 male Wistar rats in four groups of six
BPC-157

Thymosin alpha 1 improves the outcomes of patients with hepatitis B virus-related acute-on-chronic liver failure by restoring immune balance

Li ZH, Wu LL, Zhu YQ, et al. (2026). Immunopharmacology and Immunotoxicology. doi:10.1080/08923973.2026.2641686

An open-label randomised trial in 73 patients with hepatitis B-related acute-on-chronic liver failure, comparing standard medical therapy with standard therapy plus thymosin alpha 1. Thymosin alpha 1 was associated with higher 90-day transplant-free survival, fewer regulatory T cells at weeks 4 to 8 and a moderated late inflammatory response. The trial was open-label and the analysis focused on immune markers. Funding was not stated in the abstract.

human 73 patients with HBV-related ACLF, open-label RCT (NCT03082885): standard care (38) vs standard care plus thymosin alpha 1 (35)
Thymosin alpha-1

Elamipretide rejuvenates oocyte quality and restores female fertility during reproductive aging

Zhang HL, Wang Y, Wang C, et al. (2026). Aging Cell. doi:10.1111/acel.70749

A study of elamipretide in reproductive ageing. In aged mice it was associated with larger litters and better oocyte quality, with improved nuclear and cytoplasmic maturation linked to a vitamin B6-VEGF pathway. It also improved maturation, fertilisation and cleavage of aged human oocytes in the laboratory and rescued porcine oocytes under oxidative damage. The human work was on oocytes in vitro, not on women.

animal Aged mice; aged human oocytes in vitro; porcine oocytes in vitro
SS-31 (elamipretide)

Targeting mitochondrial dysfunction with elamipretide (SS-31) improves skeletal muscle performance in a HFpEF rat model

Vahle B, Weidner S, Tomalka A, et al. (2026). Circulation: Heart Failure. doi:10.1161/CIRCHEARTFAILURE.126.014397

A rat study of elamipretide in a model of heart failure with preserved ejection fraction. The model showed lower cardiolipin, weaker muscle contraction, titin hyperphosphorylation and fibre atrophy. In treated rats, whole-muscle and single-fibre contractile function and titin phosphorylation improved, atrophy was prevented, and mitochondrial function improved. The authors describe cardiolipin stabilisation as the key modulator. The study was in rats.

animal 34 HFpEF and 10 lean control female rats (12 HFpEF rats treated with elamipretide for 12 weeks)
SS-31 (elamipretide)

Neoadjuvant immunochemotherapy plus thymalfasin in locally advanced gastric cancer: a prospective clinical trial

Xu H, Li F, Li B, et al. (2026). BMC Medicine. doi:10.1186/s12916-026-04740-z

A single-arm phase II trial of anti-PD-1 (serplulimab) plus S-1/oxaliplatin chemotherapy with 9 weeks of thymalfasin (thymosin alpha 1) before surgery in 30 patients. Pathological complete response was 30.0% and major pathological response 56.7%. Adverse events of any grade occurred in 93.3% and grade 3 or higher in 26.7%. Immune profiling showed CD8+ T-cell changes. With no comparison arm, the effect of thymalfasin itself cannot be separated; the authors call for larger randomised trials.

human 30 patients with stage III gastric or gastro-oesophageal junction adenocarcinoma, single-arm phase II (NCT06461910)
Thymosin alpha-1

BPC157 drives angiogenesis through FBXO22-dependent stabilization of BACH1

Zhang J, Liu M, Ou H, et al. (2026). Cell Communication and Signaling. doi:10.1186/s12964-026-02694-6

A laboratory study of how BPC 157 may promote blood vessel growth. The authors report that BPC 157 binds the protein FBXO22 through a proline at position 3, which reduces breakdown of the transcription factor BACH1, and that higher BACH1 was linked to more proliferation and tube formation in endothelial cells. This is a proposed mechanism in cells. No competing interests were declared.

in-vitro Laboratory cell and biochemical assays (endothelial cells)
BPC-157

Effects of tirzepatide on cardiorenal biomarkers and functional capacity in heart failure: a systematic review and meta-analysis

Eisa N, Khoury M (2026). The Journal of Clinical Endocrinology & Metabolism. doi:10.1210/clinem/dgag284

A systematic review and meta-analysis of tirzepatide against placebo or standard care in heart failure and related populations. Tirzepatide was associated with a 34.3% reduction in hsCRP and a 17.6% reduction in NT-proBNP. Functional and renal results came from single trials (SUMMIT for KCCQ and 6-minute walk) and the authors call them hypothesis-generating. Registered as PROSPERO CRD42026137255.

meta-analysis 7 studies (5 RCTs, 2 observational), 5,406 participants
Tirzepatide

The mitochondrial-derived peptide MOTS-c improves bioenergetics in aging-associated granulosa cells and oocytes

Tsui KH, Cheng SH, Lin LT, et al. (2026). Reproduction and Fertility. doi:10.1530/RAF-26-0161

A laboratory study in aged human granulosa cells and eggs from aged mice. MOTS-c raised energy production, helped maintain cell structure and was associated with better egg maturation than untreated aged eggs, though not to the level of young mice. The authors state the work is not from women and did not test fertilisation, embryo development or live birth.

in-vitro Aged human granulosa cells and oocytes from aged mice, in the laboratory
MOTS-c

Mitochondria-targeted peptide elamipretide alleviates cisplatin-induced ovarian failure by activating the Nrf2/HO-1 pathway

Zhao Y, Yan H, Wang L, et al. (2026). Frontiers in Pharmacology. doi:10.3389/fphar.2026.1960111

A mouse study of elamipretide (SS31) in cisplatin-induced ovarian damage. Treated mice recovered faster, had larger ovaries, more follicles, normalised hormone levels, less oxidative stress and better mitochondrial structure in oocytes and granulosa cells, with activation of the Nrf2/HO-1 pathway. The study was in mice.

animal Mouse model of cisplatin-induced premature ovarian failure
SS-31 (elamipretide)

Endothelium-dependent nitric oxide-mediated vasorelaxant effects of BPC 157 in human internal mammary artery

Yildirim AK, Dastan AO, Demeli Ertus M, et al. (2026). Journal of Clinical Medicine. doi:10.3390/jcm15093488

An ex vivo study of residual internal mammary artery segments from 12 bypass patients. BPC 157 produced a concentration-dependent reduction in contraction, larger in rings with intact endothelium, and the effect was weakened by a nitric oxide synthase inhibitor. The authors describe it as early mechanistic evidence and call for further molecular and in vivo work.

in-vitro Artery rings from 12 patients undergoing bypass surgery, ex vivo
BPC-157

Effects of BPC-157 and TB-500 on Achilles tendon healing in rats: a histopathological and biomechanical study

Bicer O, Adanir O, Guleryuz Y, et al. (2026). Joint Diseases and Related Surgery. doi:10.52312/jdrs.2026.2951

A rat study of Achilles tendon healing after transection and repair, comparing control, BPC-157, TB-500 and the combination for four weeks. Load to failure was higher in the BPC-157 and TB-500 groups, significant only for TB-500. Tendon histology scores were better in the TB-500 and combined groups; the BPC-157-alone group trended better without reaching significance.

animal 32 male Sprague-Dawley rats, four groups of eight
BPC-157TB-500

MOTS-c is a mitochondrial-encoded interferon-linked host defense peptide

Rice MC, Imun M, Jung SW, et al. (2026). eLife. doi:10.7554/eLife.87615

A preclinical study reporting that MOTS-c has direct antibacterial activity against E. coli and MRSA, partly by acting on their membranes, and neutralised MRSA in a mouse peritonitis model. Exogenous MOTS-c during monocyte differentiation produced macrophages with altered gene expression and better bacterial clearance. One author is a consultant and shareholder of CohBar, Inc.

animal Bacteria, human and mouse monocytes, mouse peritonitis model
MOTS-c

Reparative outcomes in corneal infection: linking adjunctive Tβ4 treatment to nerve regeneration and visual function

Ebrahim AS, Liu L, Carion TW, et al. (2026). Investigative Ophthalmology & Visual Science. doi:10.1167/iovs.67.6.22

A mouse study of thymosin beta-4 added to ciprofloxacin in bacterial keratitis. The combination improved visual acuity, contrast sensitivity, corneal sensitivity and nerve regeneration compared with vehicle or either treatment alone, restoring nerve density to levels comparable to uninfected controls. The authors declare no disclosures.

animal C57BL/6 mice with Pseudomonas keratitis; thymosin beta-4 with ciprofloxacin vs each alone and vehicle
TB-500

Identification of dipeptidyl peptidase-IV inhibitory peptides from red alga dulse (Devaleraea inkyuleei) and quantification of the target peptide from in vitro digested dulse powder

Kumagai Y, Mune Mune MA, Shinohara Y, Hatanaka T (2026). Food Bioscience. doi:10.1016/j.fbio.2026.109201

A laboratory study of simulated gastrointestinal digestion of dulse (Devaleraea inkyuleei), an edible red seaweed, together with computational modelling. Digestion released EVYR, a four-amino-acid peptide, which inhibited DPP-IV, the enzyme that breaks down incretin hormones and is the target of diabetes drugs such as sitagliptin. The work was done in vitro and by computer. It was not tested in people.

in-vitro lab-only: simulated gastrointestinal digestion and computational modelling; not tested in people

Semaglutide and Panic Attacks: Active-Comparator Disproportionality Analysis, Temporal Assessment of Notoriety Bias and Evidence Triangulation in Post-Marketing Pharmacovigilance

Melamed B, Parsi-Zahabi M, Omrani MA, et al. (2026). Pharmacoepidemiology and Drug Safety. doi:10.1002/pds.70517

A pharmacovigilance database analysis by researchers at Western University of panic-attack reports for semaglutide in the FDA Adverse Event Reporting System (FAERS), checked against other evidence. Reports rose about sixfold after a July 2023 regulatory announcement, and the adjusted signal before that announcement was not significant. Across 12 studies, including randomised trials and comparison studies, the authors found no consistent rise and read the pattern as notoriety bias from publicity. The analysis shows patterns in submitted reports and does not establish cause. No conflicts were declared.

human database study: FDA FAERS reports, with evidence triangulation across 12 studies; not an enrolled trial
Semaglutide

A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Acmopatide (CT-868), a Fully Biased GLP-1/GIP Receptor Agonist, in Adults With Type 1 Diabetes and Overweight or Obesity

Klein KR, Pettus J, Sonnenberg GE, et al. (2026). Diabetes Care. doi:10.2337/dc26-1059

A phase 2, randomised, double-blind, placebo-controlled human trial in 111 adults with type 1 diabetes and a BMI of 27 or more. For 16 weeks they received a once-daily GLP-1/GIP dual agonist peptide, acmopatide (CT-868), or placebo. Body weight fell by 3.3 to 6.7% with acmopatide, against a 0.3% gain on placebo, and insulin doses fell. No diabetic ketoacidosis or severe hypoglycaemia was reported. Acmopatide is an investigational drug. Funded by Carmot Therapeutics.

human human phase 2 randomised placebo-controlled trial, n=111 adults with type 1 diabetes and a BMI of 27 or more, 16 weeks

Adjunctive recombinant human thymosin β4 therapy improves antibacterial outcomes against Staphylococcus aureus

Banga L, Patel D, Shawky M, et al. (2026). Microbiology Spectrum. doi:10.1128/spectrum.03570-25

An in vitro laboratory study from Wayne State University School of Medicine. Recombinant human thymosin beta-4, the full protein rather than the TB-500 fragment, was tested alone and alongside moxifloxacin, ciprofloxacin, oxacillin and vancomycin against Staphylococcus aureus (strain 8325-4 and two clinical isolates) in broth and biofilm assays. Alone it had little direct antibacterial effect. The authors report that combinations with antibiotics reduced bacterial growth, mainly in liquid culture, and that effects on established biofilms were limited. Not tested in animals or people.

in-vitro in vitro bacterial culture; recombinant human thymosin beta-4 (the full protein, not the TB-500 fragment); not tested in animals or people
TB-500

Associations of Serum MOTS-c with Exercise Capacity and Antioxidant Markers in Young Males: A Cross-Sectional Study

Zhang Z, Zhang X, Wang C, Zhang Y, Bo H (2026). Antioxidants. doi:10.3390/antiox15101267

A small cross-sectional study of 30 healthy men aged 18 to 25, ten each of elite track and field athletes, recreationally active men and sedentary men. Serum MOTS-c, the men's own circulating peptide, was higher in the fitter groups and correlated with VO2max and with antioxidant markers (superoxide dismutase and malondialdehyde after exercise). The authors note that the design shows an association and does not establish cause and effect. The peptide was not given to anyone. No conflicts were declared.

human small cross-sectional human study, n=30 healthy men aged 18 to 25 (10 elite athletes, 10 recreationally active, 10 sedentary); association, not a trial
MOTS-c

Targeting biglycan–TLR2/TLR4 interaction with synthetic peptides mitigates inflammation and ameliorates renal function in ischemia–reperfusion injury

Merline R, Hsieh LTH, Zeng-Brouwers J, et al. (2026). Cellular & Molecular Biology Letters. doi:10.1186/s11658-026-01019-2

A study of two synthetic peptides derived from biglycan. In laboratory assays they bound TLR2 and TLR4 and reduced biglycan-triggered inflammatory signalling in mouse and human macrophages. In mice the peptides were given before kidney ischemia-reperfusion injury. Compared with injured mice that did not receive them, the treated mice had less immune-cell infiltration, lower expression of inflammatory markers in the kidney, and lower serum creatinine. The injured groups had six mice each. An early study in mice. No competing interests were declared.

animal in mice: two biglycan-derived peptides given before kidney ischemia-reperfusion (6 treated, 6 injured controls); also macrophage assays

Bone anabolic agents repair alveolar bone damaged by diabetes in mice

Turkkahraman H, Walton CJ, Koizumi Y, et al. (2026). International Journal of Oral Science. doi:10.1038/s41368-026-00470-3

A mouse study of the FDA-approved peptides parathyroid hormone (PTH 1-34, teriparatide) and abaloparatide in alveolar bone, the jaw bone that holds the teeth. In mice with established type 2 diabetes, both peptides increased bone formation without a further rise in the already high resorption, and the authors report a net gain in alveolar bone. In non-diabetic mice the same peptides raised both formation and resorption, with no net change in alveolar bone mass. The bone-building effect required the PTH1 receptor (PTH1R) on osteocytes. This is an animal study in mice.

animal mice with established type 2 diabetes (high-fat diet and streptozotocin), non-diabetic mice, and mice lacking PTH1R in DMP1-Cre-positive cells

Continued CagriSema treatment preserves weight loss by reducing energy intake and maintaining energy expenditure in rats

Petersen LM, Knop FK, le Roux CW, et al. (2026). Molecular Metabolism. doi:10.1016/j.molmet.2026.102464

A rat study of continued cagrilintide plus semaglutide (CagriSema) in male diet-induced obese rats, compared with vehicle and with calorie restriction matched either to the treated rats' body weight or to their food intake. Over six weeks of treatment, the combination kept weight down mainly by lowering energy intake, which accounted for 86% of the weight-loss effect, while total energy expenditure was largely preserved (14%). Energy expenditure was lower in the weight-matched calorie-restricted rats. This is an animal study in rats. Several authors work in research and development at Novo Nordisk, which develops CagriSema.

animal male diet-induced obese rats; six weeks of treatment, with vehicle and calorie-restriction comparators
CagrilintideSemaglutide

Lipidated macrocyclic peptide S-880008 inhibits SARS-CoV-2 fusion by suppressing protomer dissociation at conserved spike sites

Sanaki T, Kawaguchi Y, Anraku Y, et al. (2026). Nature Communications. doi:10.1038/s41467-026-79042-2

A laboratory and mouse study of S-880008, a lipid-tagged macrocyclic peptide. It binds conserved sites on the SARS-CoV-2 spike, holding the spike protomers together and blocking viral fusion, with antiviral activity in vitro against variants including Omicron. Given intranasally to adult mice infected with SARS-CoV-2, it lowered viral titers in the lung and improved survival. This is a cell and mouse study. Several authors, including the corresponding author, are employees of Shionogi & Co., Ltd.

animal in vitro antiviral assays against SARS-CoV-2 variants, including Omicron, and adult mice infected with SARS-CoV-2

Glycemic control and weight loss benefits of fixed-ratio combinations of basal insulins and GLP1 receptor agonists in type 2 diabetes: A systematic review and network meta-analysis

Kamrul-Hasan ABM, Mondal S, Nagendra L, et al. (2026). Endocrine. doi:10.1007/s12020-026-04857-4

A network meta-analysis of 30 randomised trials in 17,862 adults with type 2 diabetes. It compared fixed-ratio combinations of a basal insulin and a GLP-1 receptor agonist with basal insulin alone. Every combination lowered HbA1c and body weight more than basal insulin alone, and more people reached an HbA1c below 7%, often without weight gain or clinically significant or severe hypoglycaemia. The combinations include IDegLira (insulin degludec with liraglutide), iGlarLixi (insulin glargine with lixisenatide), IcoSema (insulin icodec with semaglutide) and HR17031. The authors say differences between the combinations are less certain than the comparison with basal insulin alone. No competing interests were declared. Registered as PROSPERO CRD420251242577.

meta-analysis network meta-analysis of 30 randomised trials, 17,862 adults with type 2 diabetes
Semaglutide

Association of GLP-1 receptor agonist and SGLT2 inhibitor use with outcomes in patients with type 2 diabetes undergoing pacemaker implantation

Avidan Y, Jonas M, Hadar D, et al. (2026). Current Problems in Cardiology. doi:10.1016/j.cpcardiol.2026.103492

An observational study of electronic health records for 3,609 people with type 2 diabetes who had a pacemaker fitted between 2016 and 2023. The investigators are based at Lady Davis Carmel Medical Center in Haifa, Israel. People dispensed a GLP-1 receptor agonist (193), an SGLT2 inhibitor (438) or both (231) were compared with 2,747 who received neither. Over three years, each treated group had lower all-cause mortality than the neither group, and the combination was associated with the lowest (hazard ratio 0.41). The combination was also associated with fewer heart-failure hospitalisations. The authors describe an association, not cause and effect, and say randomised trials are needed. No competing interests were declared.

human observational electronic-health-record study, 3,609 adults with type 2 diabetes after pacemaker implantation; association, not a trial

Target Trial of Semaglutide Versus Dulaglutide or Liraglutide in Patients Receiving Hemodialysis

Le D, Forman E, Kraft WK, et al. (2026). Diabetes Care. doi:10.2337/dc26-2069

An observational study using US Renal Data System and Medicare records from 2011 to 2022, set up to resemble a trial. It compared semaglutide with dulaglutide or liraglutide in people with diabetes on maintenance haemodialysis. There were 1,312 semaglutide users and 2,601 dulaglutide or liraglutide users; after weighting, the effective sample was 3,200. Semaglutide was associated with a lower chance of dying while on dialysis at one year (11% versus 13%) and with more weight loss at one year (about 4.8% versus 3.4%). One-year hospitalisation was also lower (57% versus 62%). These figures come from routine-care records and show an association, not a randomised comparison. The authors conclude that semaglutide may be preferred to dulaglutide in this group.

human observational target-trial emulation, US Renal Data System and Medicare, effective n=3,200 adults with diabetes on haemodialysis (1,312 semaglutide; 2,601 dulaglutide or liraglutide before weighting)
Semaglutide

661 Retatrutide monotherapy matches the effectiveness of anti-PD-1 immunotherapy in a preclinical model of pancreatic cancer

Marathe SJ, Bohm MS, Powell Z, et al. (2025). Journal for ImmunoTherapy of Cancer (SITC 2025 abstract supplement). doi:10.1136/jitc-2025-SITC2025.0661

A conference abstract. Mice with diet-induced obesity were implanted with pancreatic cancer cells and randomised to vehicle, a low dose of retatrutide chosen not to cause weight loss, an anti-PD-1 antibody, or both, for two weeks. Retatrutide alone reduced tumour volume about three-fold versus vehicle, similar to anti-PD-1 alone (about five-fold); the combination gave no additional benefit. Body weight was stable across groups while blood glucose fell with retatrutide, which the authors take to mean the effect was independent of weight loss. Mechanism not established; abstract only, not a full peer-reviewed paper.

animal (not peer-reviewed) diet-induced obese male C57BL/6J mice with implanted pancreatic tumour cells, n=10 per group
Retatrutide

Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2, double-blind, parallel-group, placebo-controlled, randomised trial

Coskun T, Wu Q, Schloot NC, et al. (2025). The Lancet Diabetes & Endocrinology. doi:10.1016/S2213-8587(25)00092-0

A body-composition substudy of a phase 2 trial run at 42 US centres, in which adults with type 2 diabetes were randomised to weekly placebo, dulaglutide or one of several retatrutide dose groups for 36 weeks. Total fat mass was measured by DXA. Fat mass fell by roughly a quarter in the higher retatrutide groups versus about 4–5% with placebo and about 3% with dulaglutide, and the proportion of lean mass lost relative to total weight lost was reported as similar to other obesity treatments. Gastrointestinal events were the most common adverse events. Funded by Eli Lilly; all authors are Lilly employees.

human adults with type 2 diabetes, phase 2 substudy, n=189 enrolled (103 with paired DXA scans)
Retatrutide

Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity

Garvey WT, Blüher M, Osorto Contreras CK, et al. (REDEFINE 1 Study Group) (2025). New England Journal of Medicine. doi:10.1056/NEJMoa2502081

A 68-week phase 3a trial (REDEFINE 1) randomising 3,417 adults without diabetes to weekly cagrilintide plus semaglutide, semaglutide alone, cagrilintide alone, or placebo, alongside lifestyle intervention. Mean body-weight change was about -20% with the combination versus about -3% with placebo, and more participants on the combination reached weight-loss thresholds of 5% to 30%. Gastrointestinal adverse events were reported by about 80% of the combination group and about 40% of the placebo group, mostly transient and mild to moderate. Funded by Novo Nordisk.

human adults with overweight or obesity, without diabetes, phase 3a, n=3417
CagrilintideSemaglutide

Cagrilintide–Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes

Davies MJ, Bajaj HS, Broholm C, et al. (REDEFINE 2 Study Group) (2025). New England Journal of Medicine. doi:10.1056/NEJMoa2502082

A 68-week phase 3a trial (REDEFINE 2) in 12 countries randomising 1,206 adults with type 2 diabetes and a BMI of 27 or more, 3:1, to weekly cagrilintide plus semaglutide or placebo, with lifestyle intervention. Mean body-weight change was about -14% with the combination versus about -3% with placebo, and about three-quarters of the treatment group reached a glycated haemoglobin of 6.5% or lower versus 16% on placebo. Gastrointestinal adverse events were reported by about 73% of the treatment group and 34% of the placebo group, mostly mild or moderate. Funded by Novo Nordisk.

human adults with overweight or obesity and type 2 diabetes, phase 3a, n=1206
CagrilintideSemaglutide

Elamipretide: A Review of Its Structure, Mechanism of Action, and Therapeutic Potential

Tung C, Varzideh F, Farroni E, et al. (2025). International Journal of Molecular Sciences. doi:10.3390/ijms26030944

A narrative review of elamipretide (SS-31), a tetrapeptide that binds cardiolipin in the inner mitochondrial membrane. Summarises preclinical reports in models of heart failure, neurodegeneration, ischaemia-reperfusion injury, metabolic disease and muscle weakness, and outlines the clinical programme including the PROGRESS-HF, TAZPOWER, MMPOWER-3 and ReCLAIM trials. The review presents the compound favourably; the primary trial results, including the negative primary endpoint of MMPOWER-3, are listed separately on this page.

review n/a (review)
SS-31 (elamipretide)

Expanded-access use of elamipretide in a newborn with Barth syndrome: a case report

Ortmann L, Velasco D, Cole J (2025). European Heart Journal - Case Reports. doi:10.1093/ehjcr/ytaf030

A single case report of a newborn diagnosed with Barth syndrome before birth who had a dilated left ventricle with an ejection fraction of about 20% at birth and required intubation and haemodynamic support. Elamipretide was started under expanded access on day 34 alongside standard heart-failure medication. Later echocardiograms showed ejection fraction improving to near normal and the infant was discharged on day 61. The authors suggest the drug may have contributed to the improvement while acknowledging a single case with concurrent standard treatment cannot establish cause.

human single newborn with Barth syndrome, case report
SS-31 (elamipretide)

Targeting ERRs to counteract age-related muscle atrophy associated with physical inactivity: a pilot study

Bonanni R, Falvino A, Matticari A, et al. (2025). Frontiers in Physiology. doi:10.3389/fphys.2025.1616693

A pilot study in which muscle biopsies were taken from 20 women during hip replacement surgery, split by self-reported physical activity. Inactive women's muscle showed higher NOX4 and lower SIRT1, PGC-1α, ERRα and FNDC5 expression, and smaller fibre diameter. Myoblasts cultured from the inactive group were then treated with the ERR agonist SLU-PP-332, which was associated with reversal of those expression changes, less oxidative stress and senescence, and more myotube formation. The compound was applied only to cells in culture, not to people; the authors call for further mechanistic work.

in-vitro muscle biopsies from 20 women undergoing hip replacement (10 active, 10 inactive); primary myoblasts from the inactive group treated in culture
SLU-PP-332

Effects of Tesamorelin on Neurocognitive Impairment in Persons With HIV and Abdominal Obesity

Ellis RJ, Vaida F, Hu K, et al. (2025). The Journal of Infectious Diseases. doi:10.1093/infdis/jiaf012

A six-month phase 2 randomised open-label trial testing whether reducing abdominal obesity with tesamorelin improves neurocognitive performance in people with HIV. Waist circumference fell more in the tesamorelin group than in the standard-of-care group and IGF-1 rose, but neurocognitive performance did not differ significantly between the groups, and IGF-1 changes did not track with cognitive change. The authors note the study was underpowered and had no placebo arm, and conclude there is no clear cognitive benefit from short-term abdominal fat reduction with the drug.

human 73 people with HIV, virally suppressed, with abdominal obesity; phase 2, randomised, open-label against standard of care, 6 months
Tesamorelin

Semax peptide targets the mu opioid receptor gene Oprm1 to promote deubiquitination and functional recovery after spinal cord injury in female mice

Liu R, Chen Y, Huang H, et al. (2025). British Journal of Pharmacology. doi:10.1111/bph.70122

Tested semax in mice whose spinal cords had been injured by controlled impact, alongside a cell model of neuroinflammation. Treated mice recovered more movement on standard scoring, footprint and inclined-plane tests, and showed less of the lysosome-related cell death that follows spinal injury, with lower oxidative stress. Combining RNA sequencing with computational docking, the authors identify the mu opioid receptor as a target and a deubiquitinating enzyme, USP18, as the route by which the effect runs; knocking USP18 down removed the benefit. Mouse and cell work in one sex only.

animal female C57BL/6 mice with induced spinal cord injury, plus a PC12 cell neuroinflammation model
Semax

The efficacy and safety of thymosin alpha1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial

Wu J, Pei F, Zhou L, et al. (2025). BMJ. doi:10.1136/bmj-2024-082583

The largest trial of thymosin alpha-1 to date, and a negative one. Adults with sepsis at 22 Chinese centres were randomised to thymosin alpha-1 or placebo by subcutaneous injection for up to seven days. Death from any cause within 28 days occurred in 23.4 percent of the treated group and 24.1 percent of the placebo group, a difference that was not statistically significant, and no secondary or safety outcome differed either. Prespecified subgroup analysis hinted at different effects by age and by diabetes status, which the authors treat as hypothesis-generating. The conclusion is that there is no clear evidence the drug reduces 28-day mortality in sepsis.

human 1,106 adults with sepsis across 22 centres in China; phase 3, double-blind, placebo-controlled
Thymosin alpha-1

Overview of Epitalon - Highly Bioactive Pineal Tetrapeptide with Promising Properties

Araj SK, Brzezik J, Madra-Gackowska K, Szeleszczuk L (2025). International Journal of Molecular Sciences. doi:10.3390/ijms26062691

A review pulling together 25 years of work on epitalon, a four-amino-acid peptide (Ala-Glu-Asp-Gly) designed from the amino acid composition of epithalamin, an extract of the bovine pineal gland. The authors describe reported effects on melatonin synthesis, interleukin-2 messenger RNA, thymocyte activity and several enzymes including telomerase, and state that it remains uncertain whether these are the only mechanisms at work. They also note how little physico-chemical and structural work has been done on the peptide relative to the volume of biological claims. The review covers in vitro, animal and computational studies; there is no human trial in it.

review n/a (review of 25 years of in vitro, animal and computational work)
Epitalon

Tirzepatide for Obesity Treatment and Diabetes Prevention

Jastreboff AM, le Roux CW, Stefanski A, et al. (2025). New England Journal of Medicine. doi:10.1056/NEJMoa2410819

The three-year extension of SURMOUNT-1, reporting on the participants who had prediabetes as well as obesity. It covers weight change to week 176, progression to type 2 diabetes, and safety over the longer period, followed by 17 weeks off treatment, which is the part that shows what happens when the drug stops. The longest published follow-up for this compound; manufacturer-funded, like the parent trial.

human 1,032 SURMOUNT-1 participants who had both obesity and prediabetes, followed to 176 weeks plus a 17-week period off treatment
Tirzepatide

Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity

Packer M, Zile MR, Kramer CM, et al. (2025). New England Journal of Medicine. doi:10.1056/NEJMoa2410027

Tested tirzepatide in 731 people with heart failure with preserved ejection fraction and obesity, a group in which excess weight raises risk. The two primary endpoints were a composite of cardiovascular death or a worsening heart-failure event, and change in a standard heart-failure quality-of-life questionnaire at 52 weeks. Included here because it is the first cardiovascular outcome evidence for the compound rather than a weight or glucose measure.

human 731 patients with heart failure, an ejection fraction of at least 50 percent and obesity; international, double-blind, placebo-controlled, at least 52 weeks
Tirzepatide

Regeneration or Risk? A Narrative Review of BPC-157 for Musculoskeletal Healing

McGuire FP, Martinez R, Lenz A, et al. (2025). Current Reviews in Musculoskeletal Medicine. doi:10.1007/s12178-025-09990-7

A review written for musculoskeletal clinicians, prompted by how widely available BPC-157 has become and by the regulatory questions around it. It describes the compound as a synthetic 15-amino-acid peptide originally isolated from gastric juice with regenerative properties reported across numerous animal models, acting through overlapping pathways including VEGFR2 and nitric oxide synthesis via the Akt-eNOS axis, and engaging ERK1/2 signalling, with effects on blood vessel formation, fibroblast activity and neuromuscular stabilisation, particularly in poorly vascularised tissue such as tendon. The review assesses the breadth and quality of the evidence rather than assuming it, and considers safety alongside potential.

review n/a (scoping review of preclinical and clinical data)
BPC-157

Safety of Intravenous Infusion of BPC157 in Humans: A Pilot Study

Lee E, Burgess K (2025). Altern Ther Health Med. Source

A pilot safety study in two healthy adults who received BPC157 infusions, with cardiac, liver, kidney, thyroid and glucose markers measured at baseline and afterwards. The authors report no measurable effects on those markers and no adverse effects. The study did not assess efficacy, and the authors note the very small number of participants. No funding or conflicts were declared.

human 2 healthy adults; IRB-approved uncontrolled safety pilot with baseline and serial measurements
BPC-157

Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER

Thompson WR, Manuel R, Abbruscato A, et al. (2024). Genetics in Medicine. doi:10.1016/j.gim.2024.101138

Reports the 168-week open-label extension of TAZPOWER, a 28-week randomised placebo-controlled trial of elamipretide in Barth syndrome, a rare genetic mitochondrial disease. Ten patients entered the extension and eight reached week 168. Injection-site reactions were the most common adverse event. Six-minute walk distance improved from the extension baseline at every time point (about 96 metres cumulatively at week 168), fatigue scores were below baseline, and cardiac volumes and the cardiolipin ratio trended toward improvement. An uncontrolled extension in a very small group; three authors are employees of the sponsor.

human people with Barth syndrome, open-label extension, n=10 (8 reached week 168)
SS-31 (elamipretide)

Thymosin Alpha 1 Plus Routine Treatment for the Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

Cao A, Feng F, Zhou X (2024). Journal of the College of Physicians and Surgeons Pakistan. doi:10.29271/jcpsp.2024.12.1497

Pooled 39 randomised trials covering 3,329 patients having an acute flare-up of chronic obstructive pulmonary disease, comparing routine treatment with and without thymosin alpha-1. The pooled results favoured the addition on lung function, blood oxygen and carbon dioxide levels, length of hospital stay and T-cell counts. The authors state that more high-quality randomised trials are needed to confirm the effect. Most of the pooled trials were published in Chinese-language databases, and the review does not report a formal risk-of-bias result in its abstract.

meta-analysis n/a (39 randomised trials, 3,329 patients with acute exacerbation of COPD)
Thymosin alpha-1

Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity

Malhotra A, Grunstein RR, Fietze I, et al. (2024). New England Journal of Medicine. doi:10.1056/NEJMoa2404881

Two phase 3 trials testing whether tirzepatide helps obstructive sleep apnoea in people with obesity, one in participants not on positive airway pressure therapy and one in those already using it. The main measure was change in the apnoea-hypopnoea index, the number of breathing interruptions per hour of sleep. Secondary measures covered the percentage change in that index and in body weight, along with oxygen burden, patient-reported sleep disturbance and an inflammation marker. This is the evidence behind the sleep apnoea indication now on the US label.

human adults with moderate-to-severe obstructive sleep apnoea and obesity across two phase 3 trials, one in people not using positive airway pressure and one in people already using it; 52 weeks
Tirzepatide

Effect of nicotinamide riboside on airway inflammation in COPD: a randomized, placebo-controlled trial

Norheim KL, Ben Ezra M, Heckenbach I, et al. (2024). Nature Aging. doi:10.1038/s43587-024-00758-1

Forty patients with stable chronic obstructive pulmonary disease took the NAD+ precursor nicotinamide riboside or placebo for six weeks. The main measure was interleukin-8 in sputum, a marker of airway inflammation, which fell by an estimated 53 percent relative to placebo at six weeks and remained lower at follow-up twelve weeks after treatment stopped. A small trial with an inflammation marker as its endpoint rather than symptoms or lung function.

human 40 patients with stable COPD; randomised, double-blind, placebo-controlled, 6 weeks of treatment with follow-up 12 weeks later
NAD+

Nicotinamide N-methyltransferase inhibition mitigates obesity-related metabolic dysfunction

Babula JJ, Bui D, Stevenson HL, et al. (2024). Diabetes, Obesity and Metabolism. doi:10.1111/dom.15879

The most direct animal evidence for the compound itself, referred to here as 5A1MQ. Mice made obese on a high-fat diet received it daily for 28 days. The authors report that it limited gains in body weight and fat mass in a dose-dependent way, improved oral glucose tolerance and insulin sensitivity, suppressed raised insulin levels, and reduced fatty-liver changes on histology. The study also establishes how the compound behaves in the body after intravenous, oral and subcutaneous administration. Mice only; no human data exists for this compound.

animal diet-induced obese mice given the compound daily for 28 days, plus pharmacokinetic work after intravenous, oral and subcutaneous administration
5-amino-1MQ

Exploring NNMT: from metabolic pathways to therapeutic targets

Park J, Shin EJ, Kim TH, et al. (2024). Archives of Pharmacal Research. doi:10.1007/s12272-024-01519-9

A review of nicotinamide N-methyltransferase, the enzyme 5-amino-1MQ inhibits. It describes the enzyme as a link between cellular metabolism and epigenetic regulation, methylating nicotinamide using the body's universal methyl donor and so connecting one-carbon metabolism to NAD+ levels. Expression and activity differ substantially between tissues, and the review surveys the enzyme's reported roles across cancer, liver disease, obesity, diabetes, brain, lung, cardiovascular and kidney conditions. Useful for understanding why inhibiting it is being investigated, and why effects would not be confined to fat tissue.

review n/a (review)
5-amino-1MQ

Effect of BPC-157 on Symptoms in Patients with Interstitial Cystitis: A Pilot Study

Lee E, Walker C, Ayadi B (2024). Altern Ther Health Med. Source

An open-label pilot study in 12 women with interstitial cystitis who had not responded to conventional therapy. Ten of 12 reported complete resolution of symptoms after one treatment and rated it a complete success; the other two rated success at 80%. No adverse events were reported. The authors note the small sample and the absence of a control group. No funding or conflicts were declared.

human 12 women (mean age 58.3) with interstitial cystitis that had not responded to conventional therapy; open-label, uncontrolled pilot
BPC-157

Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial

Karaa A, Bertini E, Carelli V, et al. (MMPOWER-3 Trial Investigators) (2023). Neurology. doi:10.1212/WNL.0000000000207402

A phase 3, randomised, double-blind, placebo-controlled trial of 24 weeks of daily subcutaneous elamipretide in 218 adults with primary mitochondrial myopathy. The trial did not meet either primary endpoint: the difference versus placebo in six-minute walk distance was about -3 metres and the difference in the fatigue score was not significant. Elamipretide was well tolerated, with mostly mild to moderate adverse events. The authors state this provides Class I evidence that the drug does not improve walking distance or fatigue at 24 weeks in this population. Several authors report payments from the sponsor.

human adults with genetically confirmed primary mitochondrial myopathy, phase 3, n=218
SS-31 (elamipretide)

MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation

Zheng Y, Wei Z, Wang T (2023). Frontiers in Endocrinology. doi:10.3389/fendo.2023.1120533

A narrative review collecting what is known about MOTS-c: a 16-amino-acid peptide encoded in the mitochondrial 12S rRNA region, expressed in multiple tissues and present in plasma at levels that fall with age, which moves to the nucleus under metabolic stress and influences nuclear gene expression. The review covers reported effects on glucose metabolism in skeletal muscle and preclinical work in ageing, cardiovascular disease, insulin resistance and inflammation. The authors state plainly that MOTS-c has seen little use in treating disease and that no effective way of applying it in the clinic has been developed.

review n/a (narrative review)
MOTS-c

A Pilot Trial of Thymalfasin (Thymosin-alpha-1) to Treat Hospitalized Patients With Hypoxemia and Lymphocytopenia Due to Coronavirus Disease 2019 Infection

Shehadeh F, Benitez G, Mylona EK, et al. (2023). The Journal of Infectious Diseases. doi:10.1093/infdis/jiac362

A small open-label trial in 49 hospitalised COVID-19 patients with low oxygen and low lymphocyte counts, comparing thymalfasin, the synthetic form of thymosin alpha-1, against standard care. Clinical recovery was more frequent in the treated group but neither difference reached statistical significance. Among patients on low-flow oxygen, the treated group had a larger rise in CD4+ T cells by day five, which was significant. Nine serious adverse events in treated patients were judged unrelated to the drug. A pilot, open-label and underpowered by design.

human 49 hospitalised patients with COVID-19, low oxygen levels and low lymphocyte counts; open-label, randomised against standard care
Thymosin alpha-1

The efficacy of thymosin alpha-1 therapy in moderate to critical COVID-19 patients: a systematic review, meta-analysis, and meta-regression

Soeroto AY, Suryadinata H, Yanto TA, Hariyanto TI (2023). Inflammopharmacology. doi:10.1007/s10787-023-01354-2

Pooled eight studies of thymosin alpha-1 in moderate to critical COVID-19. Mortality was lower in treated patients (risk ratio 0.59), but the need for mechanical ventilation and length of hospital stay did not differ. The authors report very high statistical heterogeneity between the pooled studies, meaning the studies disagreed with each other substantially, and note that the mortality benefit was affected by sample size and by sex in meta-regression. They call for randomised trials to verify the finding.

meta-analysis n/a (pooled analysis of 8 studies in moderate to critical COVID-19)
Thymosin alpha-1

Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial

Kumar P, Liu C, Suliburk J, et al. (2023). The Journals of Gerontology: Series A. doi:10.1093/gerona/glac135

Tested whether supplying the two building blocks of glutathione, glycine and N-acetylcysteine, corrects the glutathione deficiency seen in older adults. Twenty-four older adults were randomised to the combination or an alanine placebo for 16 weeks, with twelve young adults taking the combination for two weeks as a reference. The authors report improvements in glutathione levels, oxidative stress, mitochondrial function, inflammation, insulin resistance and physical function. Participants took the precursors, not glutathione itself.

human 24 older adults randomised to GlyNAC or placebo for 16 weeks, plus 12 young adults given GlyNAC for 2 weeks as a comparison
Glutathione

A randomized placebo-controlled trial of nicotinamide riboside in older adults with mild cognitive impairment

Orr ME, Kotkowski E, Ramirez P, et al. (2023). GeroScience. doi:10.1007/s11357-023-00999-9

A pilot whose main purpose was safety: twenty older adults with mild cognitive impairment took nicotinamide riboside or placebo for ten weeks, building up to a fixed daily intake. The primary outcome was change on a standard cognitive screening test, with cerebral blood flow, blood NAD+ levels and further neurocognitive and physical tests as secondary measures, and DNA methylation as an exploratory one. Twenty people over ten weeks is a safety and feasibility study, not a test of whether the supplement helps cognition.

human 20 older adults with mild cognitive impairment; randomised placebo-controlled pilot, 10 weeks
NAD+

Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes

Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. (2023). New England Journal of Medicine. doi:10.1056/NEJMoa2307563

The SELECT trial, which asked whether semaglutide reduces cardiovascular risk in people who are overweight or obese but do not have diabetes, a question earlier trials had only answered for people with diabetes. More than 17,000 patients with existing cardiovascular disease were randomised to weekly semaglutide or placebo, with the primary endpoint a combination of death from cardiovascular causes, non-fatal heart attack and non-fatal stroke. The largest trial of any substance covered on this site, and the source of the cardiovascular claim on the semaglutide page.

human 17,604 patients aged 45 or over with existing cardiovascular disease and a BMI of 27 or more, without diabetes; multicentre, double-blind, placebo-controlled
Semaglutide

The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients With Critical COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled Trial

Youssef JG, Lavin P, Schoenfeld DA, et al. (2022). Critical Care Medicine. doi:10.1097/CCM.0000000000005660

A multicentre placebo-controlled trial randomising 196 patients with COVID-19 respiratory failure 2:1 to three days of intravenous aviptadil or placebo. The primary endpoint, being alive and free of respiratory failure at day 60, did not reach statistical significance. The authors report a secondary finding of higher odds of survival at 60 days, lower interleukin-6 by day 3, and a subgroup effect in patients on high-flow nasal oxygen at baseline. The abstract's conclusion states the primary endpoint was not met while also arguing for a favourable benefit-risk; readers should weigh the secondary analyses accordingly.

human patients with COVID-19 respiratory failure, randomised placebo-controlled trial, n=196, ten US hospitals
VIP (vasoactive intestinal peptide)

Peptides Regulating Proliferative Activity and Inflammatory Pathways in the Monocyte/Macrophage THP-1 Cell Line

Avolio F, Martinotti S, Khavinson VK, et al. (2022). International Journal of Molecular Sciences. doi:10.3390/ijms23073607

Tested five short peptides from the Khavinson series (Epitalon, Vilon, Thymogen, the Thymalin complex and Chonluten) on the human THP-1 monocyte cell line. All five altered proliferative signalling, increasing tyrosine phosphorylation of MAP kinases, and all reduced expression of TNF and IL-6 in macrophage-like cells stimulated with bacterial lipopolysaccharide; Chonluten also inhibited TNF production in monocytes. Peptide-treated cells adhered less to activated endothelial cells. The authors interpret the peptides as inducers of TNF tolerance. A single-cell-line study; one author developed the peptides.

in-vitro human THP-1 monocyte/macrophage cell line
Thymogen

Safety Profile of Bremelanotide Across the Clinical Development Program

Clayton AH, Kingsberg SA, Portman D, et al. (2022). Journal of Women's Health. doi:10.1089/jwh.2021.0191

A pooled review of safety data across the drug's whole clinical development programme. In the double-blind portion of the phase 3 studies, nausea affected 40 percent of the bremelanotide group against 1 percent on placebo, flushing 20 percent, headache 11 percent, and injection-site reactions 5 percent. Nausea was the most common reason for stopping. No deaths occurred and serious adverse events were rare. Focal hyperpigmentation was rare at the labelled frequency of use but occurred in more than a third of participants given up to 16 consecutive daily doses. Small transient blood-pressure increases were seen, and the authors advise caution in people at cardiovascular risk. Written by investigators associated with the development programme.

review n/a (pooled safety review of 43 completed studies, about 3,500 participants, phases 1 to 3)
PT-141

Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta Aggregation and Amyloid Formation in Artificial Membrane Models

Sciacca MFM, Naletova I, Giuffrida ML, Attanasio F (2022). ACS Chemical Neuroscience. doi:10.1021/acschemneuro.1c00707

A laboratory chemistry study of how semax interacts with amyloid beta, the protein that aggregates in Alzheimer's disease, in the presence of copper ions. Using fluorescence, calorimetry and cell viability assays in artificial membrane models, the authors report that semax both prevents the amyloid beta and copper complex forming and reduces aggregation and toxicity, particularly when copper is present. Work in artificial systems; it says nothing about what happens in a living brain.

in-vitro artificial membrane models and cell viability assays; no animals or people
Semax

Epitalon protects against post-ovulatory aging-related damage of mouse oocytes in vitro

Yue X, Liu SL, Guo JN, et al. (2022). Aging. doi:10.18632/aging.204007

Mouse egg cells deteriorate in the hours after ovulation; this study added epitalon to the culture medium and measured the damage at 6, 12 and 24 hours. Treated oocytes showed lower reactive oxygen species, fewer spindle defects and fewer abnormalities in cortical granule distribution, higher mitochondrial membrane potential and mitochondrial DNA copy number, and less cell death by 24 hours. The authors attribute the effect to mitochondrial activity and antioxidant action. Cells in culture; nothing here concerns fertility in a living animal or person.

in-vitro mouse oocytes aged in culture for 6, 12 and 24 hours after ovulation
Epitalon

Tirzepatide Once Weekly for the Treatment of Obesity

Jastreboff AM, Aronne LJ, Ahmad NN, et al. (2022). New England Journal of Medicine. doi:10.1056/NEJMoa2206038

The SURMOUNT-1 trial, which established tirzepatide as a weight-loss treatment. Adults with obesity, or with overweight plus a weight-related condition but not diabetes, were randomised to one of three tirzepatide levels or placebo, given by weekly injection for 72 weeks. Mean starting weight was about 105 kg. Both co-primary endpoints, percentage weight change and the proportion losing at least 5 percent, favoured tirzepatide across all three treatment groups. The trial was funded by the manufacturer.

human 2,539 adults with obesity, or overweight with a weight-related complication, excluding diabetes; phase 3, double-blind, placebo-controlled, 72 weeks
Tirzepatide

The effects of the oral supplementation of L-Cystine associated with reduced L-Glutathione-GSH on human skin pigmentation: a randomized, double-blinded, benchmark- and placebo-controlled clinical trial

Duperray J, Sergheraert R, Chalothorn K, et al. (2022). Journal of Cosmetic Dermatology. doi:10.1111/jocd.14137

A 12-week trial in 124 women testing oral glutathione for skin lightening, one of the uses it is most often sold for. Participants were randomised to a cystine and glutathione combination, glutathione alone, cystine alone, or placebo, with skin colour measured at baseline, six and twelve weeks. The proposed mechanism the authors describe is shifting melanin production toward the lighter form. Note that the trial's headline comparison is the combination product rather than glutathione on its own.

human 124 Asian female participants in four equal groups; randomised, double-blind, benchmark- and placebo-controlled, 12 weeks
Glutathione

Once-weekly semaglutide in adults with overweight or obesity

Wilding JPH, Batterham RL, Calanna S, et al. (STEP 1 Study Group) (2021). New England Journal of Medicine. doi:10.1056/NEJMoa2032183

A 68-week randomised, double-blind, placebo-controlled trial across 16 countries comparing weekly semaglutide with placebo alongside lifestyle intervention. Reported a mean body-weight change of roughly -15% in the semaglutide group versus about -2% with placebo. Gastrointestinal side effects were the most common adverse events. Industry-funded.

human adults with overweight or obesity, phase III, n=1961
Semaglutide

Senolytic Peptide FOXO4-DRI Selectively Removes Senescent Cells From in vitro Expanded Human Chondrocytes

Huang Y, He Y, Makarcyzk MJ, Lin H (2021). Frontiers in Bioengineering and Biotechnology. doi:10.3389/fbioe.2021.677576

Human chondrocytes were expanded in culture to the population-doubling level used for cartilage implantation, a process that generates senescent cells. Treatment with FOXO4-DRI removed more than half of the heavily expanded cells while leaving minimally expanded cells largely unaffected, and lowered senescence markers. Pre-treatment did not improve the cells' ability to form cartilage in pellet culture, although the tissue formed expressed fewer senescence-associated secretory factors. The authors conclude the peptide clears senescent chondrocytes but that its value for cartilage formation needs further work. A laboratory study.

in-vitro human cartilage cells from healthy donors, expanded in culture
FOXO4-DRI

EDR Peptide: Possible Mechanism of Gene Expression and Protein Synthesis Regulation Involved in the Pathogenesis of Alzheimer's Disease

Khavinson V, Linkova N, Kozhevnikova E, Trofimova S (2021). Molecules. doi:10.3390/molecules26010159

A review by the developers of the EDR tripeptide (pinealon) collecting cell, animal and small clinical reports on its neuroprotective properties and proposing a mechanism for Alzheimer's disease. The authors summarise reports that the peptide reduces neuronal apoptosis in vitro, interferes with dendritic-spine loss in neuron cultures from Alzheimer's and Huntington's model mice, and alters behaviour in animal studies, and hypothesise that it enters cells and binds histones or RNA to change MAPK/ERK signalling and expression of apoptotic and antioxidant proteins. Authored by the originating group; the mechanism is proposed, not demonstrated.

review n/a (review)
Pinealon

Vasoactive intestinal polypeptide plasma levels associated with affective symptoms and brain structure and function in healthy females

Simon RA, Barazanji N, Jones MP, et al. (2021). Scientific Reports. doi:10.1038/s41598-020-80873-2

An observational study measuring plasma VIP, anxiety and depression symptom scores, and structural and functional MRI in 37 healthy women. Higher VIP levels correlated with lower anxiety and depression scores, with greater functional connectivity between the amygdala and the parahippocampus and orbitofrontal cortex, and with larger volume in the left amygdala and left lateral orbitofrontal cortex. No VIP was administered; the study reports correlations in a small, healthy, single-sex sample and cannot establish cause.

human healthy females, n=37, observational (plasma VIP, questionnaires, MRI)
VIP (vasoactive intestinal peptide)

The Use of Thymalin for Immunocorrection and Molecular Aspects of Biological Activity

Khavinson VK, Linkova NS, Chalisova NI, Ivko OM (2021). Biology Bulletin Reviews. doi:10.1134/S2079086421040046

A narrative review of Thymalin, a calf-thymus polypeptide preparation registered in Russia, and its short-peptide components including the Glu-Trp dipeptide sold as Thymogen. Summarises the authors' account of the preparations' use in immune dysfunction, infection and post-chemotherapy recovery, and proposes mechanisms involving regulation of gene expression, heat-shock proteins, cytokines and cell differentiation. Written by the originating group; the closing suggestion that these peptides may help in COVID-19 is a hypothesis, not a trial result.

review n/a (review)
Thymogen

Thymodepressin—Unforeseen Immunosuppressor

Deigin VI, Vinogradova YE, Vinogradov DL, Krasilshchikova MS, Ivanov VT (2021). Molecules. doi:10.3390/molecules26216550

Part review, part new experiments on Thymodepressin, the D-amino-acid enantiomer of the Thymogen dipeptide, which the authors report has the opposite effect: it suppresses rather than stimulates immune responses. The historical section describes its discovery during structure-activity work on Thymogen. New experiments compared it with cyclosporin A in mice with mercury-induced autoimmunity, where Thymodepressin lowered anti-fibrillarin antibody titres in both preventive and therapeutic regimens while cyclosporin worked only preventively, and in a graft-versus-host model, where it suppressed splenomegaly more than cyclosporin. A mouse study by the compound's developers.

animal SJL/J mice in a mercury-induced autoimmunity model (5–8 per group); hybrid mice in a graft-versus-host model
Thymogen

MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis

Reynolds JC, Lai RW, Woodhead JST, et al. (2021). Nature Communications. doi:10.1038/s41467-020-20790-0

Reported that MOTS-c treatment improved physical performance in mice at three ages, and that starting intermittent treatment late in life increased physical capacity and healthspan. The authors link this to MOTS-c regulating nuclear genes involved in metabolism and protein quality control, to changes in skeletal muscle metabolism, and to how myoblasts adapt to metabolic stress. The human part of the paper is observational: exercise raised the body's own MOTS-c levels in skeletal muscle and in circulation. No MOTS-c was given to people.

animal young, middle-aged and old mice, plus measurement of MOTS-c in human skeletal muscle and blood after exercise
MOTS-c

Intra-Articular Injection of BPC 157 for Multiple Types of Knee Pain

Lee E, Padgett B (2021). Altern Ther Health Med. Source

A retrospective review of 17 patients with knee pain of several causes who had received BPC 157, alone or alongside thymosin beta-4, with follow-up by telephone. Of 12 patients who received BPC 157 alone, 91.6% reported significant improvement; of those who received it with thymosin beta-4, 75% reported improvement; overall 87.5% reported relief. There was no control group. The authors note the lack of standardised functional outcome measures and the short follow-up. No funding or conflicts were declared.

human 17 adults with knee pain, retrospective chart review with telephone follow-up, no control group
BPC-157

Intranasal Oxytocin Improves Lean Muscle Mass and Lowers LDL Cholesterol in Older Adults with Sarcopenic Obesity: A Pilot Randomized Controlled Trial

Espinoza SE, Lee JL, Wang CP, et al. (2021). Journal of the American Medical Directors Association. doi:10.1016/j.jamda.2021.04.015

A double-blind, placebo-controlled pilot trial of intranasal oxytocin in 21 older adults with obesity and slow gait speed. Oxytocin was reported as well tolerated without significant adverse events. Whole-body lean mass rose by 2.25 kg compared with placebo and LDL cholesterol fell by 19.3 mg/dL, with a non-significant trend to lower fat mass. BMI, appetite, glycaemia, HDL, triglycerides and depressive symptoms did not change significantly. The trial was small and described by the authors as proof of concept. No conflicts were declared.

human 21 older adults with obesity and slow gait speed, double-blind placebo-controlled pilot RCT, 8 weeks

FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice

Zhang C, Xie Y, Chen H, et al. (2020). Aging. doi:10.18632/aging.102682

Examined FOXO4 in testosterone-producing Leydig cells. In human tissue the authors found FOXO4 expressed in Leydig cells, with nuclear localisation in older men linked to lower testosterone synthesis. In a cell model of senescence induced by hydrogen peroxide, FOXO4-DRI selectively triggered apoptosis of senescent Leydig cells. In naturally aged mice the peptide was associated with changes in the testicular microenvironment and higher testosterone secretion. A cell and mouse study; no human treatment.

animal senescent TM3 Leydig cells in culture; naturally aged mice
FOXO4-DRI

Comparison of the Effects of KE and AED Peptides on Functional Activity of Human Skin Fibroblasts during Their Replicative Aging

Fridman NV, et al. (2020). Bulletin of Experimental Biology and Medicine. doi:10.1007/s10517-020-05022-1

A cell study comparing the KE and AED short peptides in ageing human skin fibroblasts. The KE peptide lowered markers of inflammation (IL-1, NF-kB, TGF-beta) and raised sirtuin-6, while the AED peptide raised sirtuin-1, sirtuin-6 and collagen I. The work was done in cultured cells only, with no animal or human validation.

in-vitro aged human skin fibroblast cultures

Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials

Kingsberg SA, Clayton AH, Portman D, et al. (2019). Obstetrics & Gynecology. doi:10.1097/AOG.0000000000003500

The two phase 3 trials behind the drug's US approval. Premenopausal women with hypoactive sexual desire disorder were randomised to bremelanotide, self-administered subcutaneously as needed, or placebo for 24 weeks. Both co-primary endpoints favoured bremelanotide: sexual desire scores rose and distress related to low desire fell, with statistically significant differences from placebo in both studies. The size of the change was small in absolute terms, around a third of a point on each scale. Nausea, flushing and headache each affected at least one in ten participants in both studies. Funded by the companies developing the drug.

human 1,267 premenopausal women with hypoactive sexual desire disorder across two identical phase 3 trials (RECONNECT), randomised, double-blind, placebo-controlled, 24 weeks
PT-141

Selank, Peptide Analogue of Tuftsin, Protects Against Ethanol-Induced Memory Impairment by Regulating of BDNF Content in the Hippocampus and Prefrontal Cortex in Rats

Kolik LG, Nadorova AV, Antipova TA, et al. (2019). Bulletin of Experimental Biology and Medicine. doi:10.1007/s10517-019-04588-9

Looked at whether selank affects the memory problems that follow long-term alcohol exposure in rats, and at BDNF, a nerve growth factor, in two brain regions. In rats that had drunk ethanol for 30 weeks, selank prevented the memory and attention disturbances that developed during withdrawal, and in unexposed older rats it improved object recognition. It also prevented the ethanol-driven rise in BDNF in the hippocampus and frontal cortex. A rat study; the authors present BDNF regulation as the mechanism.

animal outbred rats given ethanol as their only fluid for 30 weeks, tested on object recognition
Selank

Regenerative and protective actions of the GHK-Cu peptide in the light of the new gene data

Pickart L, Margolina A (2018). International Journal of Molecular Sciences. doi:10.3390/ijms19071987

A review collecting cell, animal and gene-expression studies on GHK-Cu, covering reported effects on wound healing, collagen production and skin. The lead author is the peptide's original discoverer and has commercial interests in it, which readers should weigh when assessing the review's framing.

review n/a (review)
GHK-Cu

The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress

Kim KH, Son JM, Benayoun BA, Lee C (2018). Cell Metabolism. doi:10.1016/j.cmet.2018.06.008

A mechanism study. The authors showed that MOTS-c moves from the mitochondria into the cell nucleus after metabolic stress, in a way that depends on AMPK, and there influences a broad set of nuclear genes, including genes carrying antioxidant response elements. MOTS-c was found to interact with stress-responsive transcription factors such as NRF2. The authors present this as evidence that the mitochondrial and nuclear genomes each encode factors that regulate the other. Cell work only.

in-vitro cultured cells under glucose restriction and other metabolic stress
MOTS-c

The efficacy of semax in the treatment of patients at different stages of ischemic stroke

Gusev EI, Martynov MY, Kostenko EV, et al. (2018). Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. doi:10.17116/jnevro20181183261-68

A Russian study of 110 people recovering from ischaemic stroke, divided into early and late rehabilitation groups, each further split by whether semax was given alongside rehabilitation. The authors report that semax raised plasma BDNF, a nerve growth factor, and that this stayed elevated through the study; Barthel index scores, a measure of independence in daily activities, improved faster and ended higher in the semax groups, and motor performance correlated with early rehabilitation. The report describes group comparisons rather than a randomised placebo-controlled design, and the peptide is in routine clinical use in the country where the study was run.

human 110 people after ischaemic stroke (43 men, 67 women, mean age 58), split by early or late rehabilitation and by whether semax was given
Semax

Peptide-based Anxiolytics: The Molecular Aspects of Heptapeptide Selank Biological Activity

Vyunova TV, Andreeva L, Shevchenko K, Myasoedov N (2018). Protein & Peptide Letters. doi:10.2174/0929866525666180925144642

A mechanism study using radioligand binding on isolated brain cell membranes to ask how selank, a seven-amino-acid analogue of the natural peptide tuftsin, might produce anxiety-reducing effects. The authors report that selank acts as a positive allosteric modulator of GABA binding, the same broad system benzodiazepines act on, and that its combined action with benzodiazepines is not simply additive: selank could block the modulating activity of diazepam and olanzapine, suggesting overlapping but not identical binding sites. Laboratory binding work, not a behavioural or clinical result.

in-vitro isolated brain cell membranes, radioligand binding assays
Selank

Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults

Martens CR, Denman BA, Mazzo MR, et al. (2018). Nature Communications. doi:10.1038/s41467-018-03421-7

A crossover trial in healthy middle-aged and older adults testing whether the NAD+ precursor nicotinamide riboside is tolerated and whether it actually raises NAD+ in people. It was well tolerated and did stimulate NAD+ metabolism. On physiological function the authors report initial signals rather than conclusions, suggesting that future trials look specifically at blood pressure and arterial stiffness. Target engagement demonstrated; clinical benefit not.

human healthy middle-aged and older adults, randomised double-blind placebo-controlled crossover, two 6-week periods
NAD+

Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice

Neelakantan H, Vance V, Wetzel MD, et al. (2018). Biochemical Pharmacology. doi:10.1016/j.bcp.2017.11.007

The study that put this class of compound on the map. The authors tested a series of small-molecule inhibitors of nicotinamide N-methyltransferase, an enzyme involved in cellular metabolism and energy balance, for their ability to cross membranes and act selectively against related enzymes. In cultured fat cells the inhibitors affected fat synthesis and the enzyme's reaction product. A potent inhibitor from the series was then tested in mice made obese by a high-fat diet, where the authors report reversal of the diet-induced obesity. Cell and mouse work aimed at validating the enzyme as a drug target.

animal cultured adipocytes and permeability assays, then mice made obese on a high-fat diet
5-amino-1MQ

A small molecule inhibitor of Nicotinamide N-methyltransferase for the treatment of metabolic disorders

Kannt A, Rajagopal S, Kadnur SV, et al. (2018). Scientific Reports. doi:10.1038/s41598-018-22081-7

Reports a different small-molecule inhibitor of the same enzyme, JBSNF-000088, rather than 5-amino-1MQ itself. In mice made obese on a high-fat diet it reduced body weight, improved insulin sensitivity and normalised glucose tolerance to the level of lean controls; the effects were absent in mice lacking the enzyme, which the authors take as confirmation the compound works through it. In two genetic obesity models the glucose effects were smaller and came without weight loss. Included because it is the strongest specificity evidence for the target, not because it tests the compound sold by suppliers.

animal diet-induced obese mice, ob/ob and db/db mice, and NNMT knockout mice as a specificity control
5-amino-1MQ

Thymosin beta 4 and the eye: the journey from bench to bedside

Sosne G (2018). Expert Opinion on Biological Therapy. doi:10.1080/14712598.2018.1486818

A first-person account by one of the investigators of how thymosin beta-4 moved from laboratory work into eye clinics, covering its applications in ocular repair and reporting that phase 3 clinical trials of the peptide in dry eye and neurotrophic keratopathy were under way at the time of writing. It is the clearest published statement that the molecule reached late-stage human trials, and it is explicitly a personal narrative rather than a systematic review. As with the cardiac work, the trials concern the full protein rather than the TB-500 fragment.

review n/a (narrative review by an investigator in the field)
TB-500

Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging

Baar MP, Brandt RMC, Putavet DA, et al. (2017). Cell. doi:10.1016/j.cell.2017.02.031

The paper that introduced FOXO4-DRI. The authors identified the transcription factor FOXO4 as important for the survival of senescent cells and designed a peptide that disrupts its interaction with p53. In culture, the peptide caused senescent cells, but not normal cells, to undergo apoptosis. In mice it reduced the toxicity of the chemotherapy drug doxorubicin and, in both a fast-ageing strain and naturally aged animals, was associated with improved fitness, fur density and kidney function. A mouse and cell study from the group that developed the peptide.

animal cultured senescent cells; fast-ageing (XpdTTD/TTD) and naturally aged mice
FOXO4-DRI

Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis

Xiao B, Xu Z, Viennois E, et al. (2017). Molecular Therapy. doi:10.1016/j.ymthe.2016.11.020

A drug-delivery study rather than a study of KPV itself. The authors loaded KPV into hyaluronic-acid-coated polymer nanoparticles designed to be taken up by colonic epithelial cells and macrophages, then encapsulated those particles in a chitosan/alginate hydrogel so they would survive oral delivery and release in the colon. In cell culture the particles were taken up by the target cell types without apparent toxicity; in a mouse colitis model the hydrogel-encapsulated particles reduced mucosal damage and lowered TNF-alpha more than KPV-loaded particles without the hyaluronic acid coating. Mouse and cell work; nothing here bears on oral KPV taken without such a carrier.

animal cultured intestinal cells and macrophages, then mice with induced ulcerative colitis
KPV

Safety and metabolic effects of tesamorelin, a growth hormone-releasing factor analogue, in patients with type 2 diabetes: A randomized, placebo-controlled trial

Clemmons DR, Miller S, Mamputu JC (2017). PLOS ONE. doi:10.1371/journal.pone.0179538

A safety trial addressing the concern that growth hormone and related compounds worsen insulin sensitivity. Fifty-three people with type 2 diabetes were randomised to placebo or one of two tesamorelin groups for 12 weeks. Insulin response to an oral glucose load did not differ significantly between groups, and neither did fasting glucose, HbA1c or overall diabetes control at 12 weeks. Total and non-HDL cholesterol fell in the higher tesamorelin group relative to placebo. No participant stopped the study because diabetes control was lost. Small and short.

human 53 people with type 2 diabetes, randomised to placebo or one of two tesamorelin groups, 12 weeks
Tesamorelin

Peptide Selank Enhances the Effect of Diazepam in Reducing Anxiety in Unpredictable Chronic Mild Stress Conditions in Rats

Kasian A, Kolomin T, Andreeva L, et al. (2017). Behavioural Neurology. doi:10.1155/2017/5091027

Compared selank, diazepam and the two together in rats, with and without chronic unpredictable stress, using the elevated plus maze as the anxiety measure. Given alone, selank was the most effective at reducing the raised anxiety that a course of the test substances itself produced; under chronic stress, the combination of diazepam and selank brought anxiety measures back to pre-stress values. The authors read this as evidence that selank changes how classical benzodiazepines act rather than simply adding to them. A rat behavioural study.

animal rats under unpredictable chronic mild stress and unstressed controls, tested on the elevated plus maze
Selank

Brain-gut axis and pentadecapeptide BPC 157: theoretical and practical implications

Sikiric P, Seiwerth S, Rucman R, et al. (2016). Current Neuropharmacology. doi:10.2174/1570159X13666160502153022

A narrative review from the group responsible for most BPC-157 research, summarising their animal studies on gut, tendon, muscle and nervous system tissue and proposing a role for the peptide in the brain-gut axis. As a review by the originating group, it collects that group's findings rather than independently replicating them.

review n/a (review)
BPC-157

Bremelanotide for Female Sexual Dysfunctions in Premenopausal Women: A Randomized, Placebo-Controlled Dose-Finding Trial

Clayton AH, Althof SE, Kingsberg S, et al. (2016). Women's Health. doi:10.2217/whe-2016-0018

The phase 2b dose-finding trial that set up the phase 3 programme. Premenopausal women with female sexual dysfunction self-administered bremelanotide or placebo subcutaneously as desired over 12 weeks. Pooling the two higher bremelanotide groups against placebo, the number of satisfying sexual events per month rose by about half an event more than placebo, with improvements on the Female Sexual Function Index and the associated distress scale. Reported adverse events were nausea, flushing and headache.

human 327 premenopausal women with female sexual dysfunction (efficacy population), randomised to placebo or one of three bremelanotide groups, 12 weeks
PT-141

Correction of impaired glucose tolerance using tetrapeptide (Pancragen) in old female rhesus monkeys

Goncharova ND, Ivanova LG, Oganyan TE, Vengerin AA, Khavinson VK (2015). Advances in Gerontology (Uspekhi Gerontologii). Source

Compared pancragen with the sulfonylurea drug glimepiride in nine old female rhesus monkeys, five receiving a ten-day intramuscular course of pancragen and four an oral course of glimepiride. Blood glucose, insulin and C-peptide were measured before, during and after treatment and during glucose tolerance tests. Both treatments lowered basal glucose; pancragen was also associated with normalised insulin and C-peptide levels, whereas glimepiride produced a stronger, delayed glucose-lowering effect and stimulated C-peptide without changing insulin. Very small groups, no placebo arm, Russian-language paper with an English abstract.

animal old female rhesus monkeys (20–25 years), n=9 (5 pancragen, 4 glimepiride)
Pancragen

The Mitochondrial-Derived Peptide MOTS-c Promotes Metabolic Homeostasis and Reduces Obesity and Insulin Resistance

Lee C, Zeng J, Drew BG, et al. (2015). Cell Metabolism. doi:10.1016/j.cmet.2015.02.009

The paper that identified MOTS-c. The authors found a short open reading frame inside the mitochondrial 12S rRNA gene encoding a 16-amino-acid peptide, and reported that it acts mainly on skeletal muscle, inhibiting the folate cycle and the purine synthesis tethered to it, which in turn activates AMPK. In mice, MOTS-c treatment prevented the insulin resistance that comes with age and with a high-fat diet, and prevented diet-induced obesity. Cell and mouse work; the finding of interest is that the mitochondrial genome encodes a signalling peptide at all.

animal cell culture, then mice (age-related and high-fat-diet models of insulin resistance)
MOTS-c

Optimization of the treatment of anxiety disorders with selank

Medvedev VE, Tereshchenko ON, Kost NV, et al. (2015). Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. doi:10.17116/jnevro20151156133-40

A Russian comparison of a benzodiazepine (phenazepam) alone against the same drug with selank added, in 70 people with anxiety-phobic, hypochondriac and somatoform disorders. The authors report that the benzodiazepine's effect appeared earlier when selank was added, and that the combination reduced the benzodiazepine's side effects, including attention and memory impairment, sedation, longer sleep and emotional flatness, both during treatment and after the benzodiazepine was withdrawn. Quality-of-life scores were better in the combination group. An add-on comparison in a small group, not a placebo-controlled trial of selank by itself.

human 70 people with anxiety disorders: 30 on a benzodiazepine alone, 40 on the benzodiazepine plus selank
Selank

Randomized controlled trial of oral glutathione supplementation on body stores of glutathione

Richie JP, Nichenametla S, Neidig W, et al. (2015). European Journal of Nutrition. doi:10.1007/s00394-014-0706-z

Asked whether swallowing glutathione raises the body's own stores of it, which had been shown in animals but not in people. Fifty-four non-smoking adults took one of two oral amounts or placebo for six months, with glutathione measured in blood, red cells, plasma, lymphocytes and cheek cells. Levels rose at one, three and six months at both amounts; by six months the higher-intake group was up by roughly a third in red cells, plasma and lymphocytes and far more in cheek cells, while the lower-intake group rose in blood and red cells. The study measures body stores, not health outcomes.

human 54 non-smoking adults, randomised double-blind placebo-controlled, 6 months
Glutathione

Study of interactions between DNA and tetrapeptides using methods of molecular mechanics

Tarnovskaya SI, Yakutseni PP, Khavinson VKh (2014). Bulletin of Experimental Biology and Medicine. doi:10.1007/s10517-014-2426-z

A molecular-modelling study of how the tetrapeptide Lys-Glu-Asp-Trp (pancragen) might bind DNA. The simulations suggest the peptide can sit in both the minor and major groove of the double helix, with major-groove binding depending on the sequences of both peptide and DNA, and propose GGCAG as a candidate binding site. Entirely computational; no experimental binding data are reported in the abstract.

in-vitro computational molecular modelling; no cells or animals
Pancragen

Effect of Tesamorelin on Visceral Fat and Liver Fat in HIV-Infected Patients With Abdominal Fat Accumulation: A Randomized Clinical Trial

Stanley TL, Feldpausch MN, Oh J, et al. (2014). JAMA. doi:10.1001/jama.2014.8334

A single-centre randomised placebo-controlled trial asking whether tesamorelin affects liver fat as well as visceral fat in people with HIV and abdominal fat accumulation. Over six months, visceral adipose tissue and liver fat both fell in the treated group relative to placebo. Fasting glucose was higher in the treated group at two weeks, but the difference was no longer significant at six months. Fifty participants at one hospital, so small; investigator-initiated rather than company-run.

human 50 people with HIV on antiretroviral therapy with abdominal fat accumulation, randomised, double-blind, placebo-controlled, 6 months
Tesamorelin

The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis

Medvedeva EV, Dmitrieva VG, Povarova OV, et al. (2014). BMC Genomics. doi:10.1186/1471-2164-15-228

A genome-wide look at what semax does to gene expression in the brain tissue of rats after an induced stroke, sampled at 3 and 24 hours. Genes related to the immune system dominated the response: by 24 hours they made up over half the genes whose expression semax altered, with immunoglobulin and chemokine genes the most prominent groups. A smaller set of genes related to blood vessel development and function also changed. The authors propose immune modulation and effects on the vascular system as the mechanisms behind the neuroprotective effects reported elsewhere; the study measures gene expression, not recovery.

animal rats with permanent middle cerebral artery occlusion, cortex sampled at 3 and 24 hours
Semax

Prospective, randomized, controlled, proof-of-concept study of the Ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients

Beck DE, Sweeney WB, McCarter MD, Beart R (2014). International Journal of Colorectal Disease. doi:10.1007/s00384-014-2030-8

The one human trial of ipamorelin in the literature reviewed for this page. Adults having bowel surgery received intravenous ipamorelin or placebo twice daily from the first day after surgery until discharge, testing whether stimulating the ghrelin receptor helps the gut start working again afterwards. The key efficacy measure was the time from the first administration to tolerating a standard solid meal, with safety tracked through adverse events and laboratory tests. A proof-of-concept study in around a hundred patients, not a trial designed to establish effectiveness.

human 117 adults enrolled undergoing open or laparoscopic bowel resection, 114 analysed; phase 2, multicentre, double-blind, placebo-controlled
Ipamorelin

Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial

Grönberg A, et al. (2014). Wound Repair and Regeneration. doi:10.1111/wrr.12211

A double-blind, placebo-controlled randomised trial in 34 patients with hard-to-heal venous leg ulcers, with a three-week run-in and a four-week treatment phase of topical LL-37. At the lower tested strengths the ulcer healing rate was about six times that of placebo, with a mean ulcer area reduction of 68%. No safety concerns were reported. The authors note that the highest tested strength did not show the same effect.

human 34 patients with hard-to-heal venous leg ulcers; double-blind, placebo-controlled randomised trial

Disease modifying effect of chronic oral treatment with a neurotrophic peptidergic compound in a triple transgenic mouse model of Alzheimer's disease

Kazim SF, et al. (2014). Neurobiology of Disease. doi:10.1016/j.nbd.2014.07.001

A twelve-month study in triple-transgenic Alzheimer's mice and wild-type controls. The P021 peptide compound reduced tau hyperphosphorylation, lowered soluble amyloid-beta and rescued cognitive deficits and synaptic plasticity, with the authors pointing to a BDNF-linked mechanism. The authors note the effect was mainly on tau rather than amyloid pathology. This is an animal study; there are no human trials.

animal triple-transgenic Alzheimer's mice and wild-type controls; twelve-month study

Effects of pancragen on the differentiation of pancreatic cells during their ageing

Khavinson VKh, Durnova AO, Polyakova VO, et al. (2013). Bulletin of Experimental Biology and Medicine. doi:10.1007/s10517-013-1987-6

Measured expression of transcription factors that drive pancreatic cell differentiation in 'young' and 'aged' pancreatic cell cultures with and without pancragen. Expression of the markers fell with culture ageing; pancragen was associated with higher expression of acinar-cell factors (Pdx1, Ptf1a) and islet-cell factors (Pdx1, Pax6, Pax4, Foxa2, Nkx2.2) in both young and aged cultures. The authors propose this as a mechanism for the anti-diabetic effects they report elsewhere. A cell-culture study; species of the cultures is not stated in the abstract.

in-vitro 'young' and 'aged' pancreatic cell cultures
Pancragen

Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study

Heij L, et al. (2012). Molecular Medicine. doi:10.2119/molmed.2012.00332

A randomised, double-blind, placebo-controlled pilot in 22 sarcoidosis patients with symptoms of small fibre neuropathy (12 given ARA 290, 10 placebo) over four weeks. The ARA 290 group improved more than placebo on a small fibre neuropathy screening score, and improved from baseline on the pain and physical-functioning parts of a quality-of-life questionnaire. Pain intensity and fatigue scores improved in both groups to a similar degree, and depressive symptoms did not change. No safety concerns were identified. The authors describe it as an exploratory pilot.

human 22 patients with sarcoidosis and small fibre neuropathy symptoms; randomised, double-blind, placebo-controlled pilot

The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration

Chang CH, Tsai WC, Lin MS, Hsu YH, Pang JH (2011). Journal of Applied Physiology. doi:10.1152/japplphysiol.00945.2010

Examined BPC-157 on rat Achilles tendon explants and cultured tendon fibroblasts. Reported increased outgrowth of tendon tissue from explants, improved cell survival under oxidative stress, and increased cell migration, with the authors linking these to a specific signalling pathway. A laboratory study; no live animals or humans were treated.

in-vitro rat tendon explants and cultured tendon cells
BPC-157

Pinealon Increases Cell Viability by Suppression of Free Radical Levels and Activating Proliferative Processes

Khavinson V, Ribakova Y, Kulebiakin K, et al. (2011). Rejuvenation Research. doi:10.1089/rej.2011.1172

Exposed cultured cerebellar granule cells, neutrophils and PC12 cells to oxidative stress with and without the tripeptide pinealon (Glu-Asp-Arg). Pinealon was associated with lower accumulation of reactive oxygen species and less necrotic cell death, with a delayed time course of ERK1/2 activation and changes in the cell cycle. Because the antioxidant effect saturated at low concentrations while cell-cycle effects continued at higher ones, the authors propose the peptide may act on the genome directly. A cell study from the group that developed the peptide.

in-vitro rat cerebellar granule cells, neutrophils and PC12 cells in culture
Pinealon

Study of biological activity of Lys-Glu-Asp-Trp-NH2 endogenous tetrapeptide

Khavinson VKh, Gapparov MM, Sharanova NE, Vasilyev AV, Ryzhak GA (2010). Bulletin of Experimental Biology and Medicine. doi:10.1007/s10517-010-0944-x

Evaluated the biological effect of the tetrapeptide Lys-Glu-Asp-Trp-NH2 (pancragen) in rats during normal development and in streptozotocin-induced diabetes, which the authors use as a model of accelerated ageing, by measuring a set of metabolic parameters related to apoptosis. The abstract is a single sentence and reports no numerical results; the full text was not read.

animal rats during development and with streptozotocin-induced diabetes
Pancragen

Effects of Tesamorelin, a Growth Hormone-Releasing Factor, in HIV-Infected Patients With Abdominal Fat Accumulation: A Randomized Placebo-Controlled Trial With a Safety Extension

Falutz J, Potvin D, Mamputu JC, et al. (2010). JAIDS Journal of Acquired Immune Deficiency Syndromes. doi:10.1097/QAI.0b013e3181cbdaff

A 12-month randomised double-blind trial in people with HIV on antiretroviral therapy who had excess abdominal fat. Over the first six months, visceral adipose tissue fell by about 11 percent in the tesamorelin group against under 1 percent on placebo, with improvements in trunk fat, waist circumference and waist-to-hip ratio and no change in limb or subcutaneous abdominal fat. IGF-1 rose; glucose measures did not change. Participants and physicians both rated abdominal appearance as improved. Those who continued for 12 months reached about an 18 percent reduction, and those switched from tesamorelin to placebo rapidly lost the gain. One of the two trials behind the drug's US approval.

human 404 people with HIV on antiretroviral therapy with excess abdominal fat, randomised, double-blind, 12 months
Tesamorelin

Randomized, double-blind, pilot evaluation of intravenous glutathione in Parkinson's disease

Hauser RA, Lyons KE, McClain T, et al. (2009). Movement Disorders. doi:10.1002/mds.22401

A small placebo-controlled pilot of intravenous glutathione in 21 people with Parkinson's disease whose motor symptoms were not adequately controlled by their existing medication, given three times a week for four weeks. It was well tolerated, with no withdrawals for adverse events and similar adverse events in both groups, but there were no significant differences in Unified Parkinson's Disease Rating Scale scores between glutathione and placebo. A negative pilot, and the main published trial of glutathione given by infusion.

human 21 people with Parkinson's disease whose symptoms were not well controlled on existing medication; randomised, double-blind, placebo-controlled, 4 weeks
Glutathione

Inhalation of vasoactive intestinal peptide in pulmonary hypertension

Leuchte HH, Baezner C, Baumgartner RA, et al. (2008). European Respiratory Journal. doi:10.1183/09031936.00050008

Twenty patients with pulmonary hypertension of mixed causes inhaled a single dose of aviptadil (synthetic VIP) during right-heart catheterisation while haemodynamics and blood gases were measured. The authors report a small, temporary but statistically significant selective reduction in pulmonary vascular resistance, improved stroke volume and mixed venous oxygen saturation, with no side effects and no change in systemic blood pressure. Six patients had a pulmonary vascular resistance reduction of more than 20%. An acute, uncontrolled, single-dose study; the authors call for larger and longer trials.

human patients with pulmonary hypertension, n=20, single inhaled dose during catheterisation
VIP (vasoactive intestinal peptide)

PepT1-Mediated Tripeptide KPV Uptake Reduces Intestinal Inflammation

Dalmasso G, Charrier-Hisamuddin L, Nguyen HTT, et al. (2008). Gastroenterology. doi:10.1053/j.gastro.2007.10.026

Asked how KPV, a three-amino-acid fragment of alpha-MSH, reaches the inside of cells and whether that explains its anti-inflammatory effect. In human intestinal epithelial and T cell lines stimulated with inflammatory cytokines, KPV at nanomolar concentrations reduced NF-kB and MAP kinase signalling and lowered pro-inflammatory cytokine output; uptake experiments indicated the peptide enters through PepT1, a di- and tripeptide transporter expressed in the small intestine and induced in the colon during inflammatory bowel disease. In mice, KPV given in drinking water reduced the severity of chemically induced colitis measured by tissue damage and cytokine expression. Cell and mouse work only; the authors describe KPV as a possible therapeutic candidate rather than a treatment.

animal human intestinal epithelial and T cell lines, plus mice in two colitis models (DSS and TNBS)
KPV

Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease

Kannengiesser K, Maaser C, Heidemann J, et al. (2008). Inflammatory Bowel Diseases. doi:10.1002/ibd.20334

Tested KPV in two established mouse models of inflammatory bowel disease. In DSS colitis, treated mice recovered earlier and regained more body weight than controls, with less inflammatory infiltrate on histology and lower myeloperoxidase activity in colonic tissue; in transfer colitis the pattern was similar. In mice whose melanocortin-1 receptor does not function, KPV treatment still prevented deaths during DSS colitis, which the authors read as evidence that at least part of the effect does not depend on that receptor. An animal study; the authors describe KPV as an interesting therapeutic option to investigate, not an established one.

animal mice, two colitis models (DSS colitis and CD45RB-high transfer colitis), plus mice carrying a non-functional melanocortin-1 receptor
KPV

Salvage of Sildenafil Failures With Bremelanotide: A Randomized, Double-Blind, Placebo Controlled Study

Safarinejad MR, Hosseini SY (2008). Journal of Urology. doi:10.1016/j.juro.2007.10.063

A randomised double-blind placebo-controlled trial of intranasal bremelanotide in men with erectile dysfunction who had not responded to sildenafil. About a third of the bremelanotide group showed a positive clinical result against under a tenth on placebo, with higher reported intercourse satisfaction, and more drug-related adverse effects. The authors call it a possible alternative treatment and say further work on dose and regimen is needed to draw conclusions. This intranasal line of development was later discontinued; the approved product is a subcutaneous injection for a different indication in women.

human 342 men aged 28 to 59 with erectile dysfunction not responding to sildenafil, randomised to intranasal bremelanotide or placebo
PT-141

Effect of pancragen on blood glucose level, capillary permeability and adhesion in rats with experimental diabetes mellitus

Khavinson VKh, Gavrisheva NA, Malinin VV, Chefu SG, Trofimov EL (2007). Bulletin of Experimental Biology and Medicine. doi:10.1007/s10517-007-0377-3

Studied the tetrapeptide pancragen (Lys-Glu-Asp-Trp-NH2) in Wistar rats made diabetic with streptozotocin, measuring blood glucose and the permeability and adhesion of mesenteric capillaries. Oral pancragen was associated with lower blood glucose during treatment; intramuscular pancragen normalised endothelial adhesion but did not change capillary permeability. The authors describe the results as homeostatic and endothelium-protective effects early in diabetes. A short rat study from the developing group; the abstract gives no group sizes.

animal Wistar rats with streptozotocin-induced diabetes
Pancragen

Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults

Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA (2006). Journal of Clinical Endocrinology & Metabolism. doi:10.1210/jc.2005-1536

Two early-phase studies in healthy adults measuring growth hormone and IGF-1 levels after single or repeated administration of CJC-1295. Reported sustained increases in both hormones lasting several days after a single administration. Small, short, and designed to characterise the compound rather than test a clinical outcome.

human healthy adults, phase I, two small dose-ranging studies
CJC-1295

Effects of the COOH-terminal tripeptide alpha-MSH(11-13) on corneal epithelial wound healing: role of nitric oxide

Bonfiglio V, Camillieri G, Avitabile T, et al. (2006). Experimental Eye Research. doi:10.1016/j.exer.2006.07.014

Examined topical KPV, the C-terminal tripeptide of alpha-MSH, on corneal healing in rabbits whose corneal epithelium had been mechanically removed. Eyes treated with KPV, and eyes treated with a nitric oxide donor, closed the epithelial defect faster than eyes given vehicle, with all treated corneas fully re-covered by 60 hours while none of the placebo corneas were. Pre-treating with a nitric oxide synthase inhibitor blocked the effect, which the authors take as evidence that nitric oxide is involved. A rabbit study with a cell-culture component; no human data.

animal rabbits with surgically abraded corneal epithelium in both eyes, plus cultured rabbit corneal epithelial cells
KPV

Pulsatile Secretion of Growth Hormone (GH) Persists during Continuous Stimulation by CJC-1295, a Long-Acting GH-Releasing Hormone Analog

Ionescu M, Frohman LA (2006). The Journal of Clinical Endocrinology & Metabolism. doi:10.1210/jc.2006-1702

Asked whether a growth hormone-releasing analogue that acts continuously flattens out the body's natural pulses of growth hormone, which are thought to matter for its effects. Healthy men were sampled overnight before and a week after a single injection. Growth hormone secretion increased and the pulsatile pattern was preserved rather than blunted. The paper describes the compound as binding permanently to the body's own albumin after injection, which is what gives it a half-life of about eight days.

human healthy men aged 20 to 40, blood sampled every 20 minutes over a 12-hour overnight period before and a week after a single injection
CJC-1295

Thymosin β4: actin-sequestering protein moonlights to repair injured tissues

Goldstein AL, Hannappel E, Kleinman HK (2005). Trends in Molecular Medicine. doi:10.1016/j.molmed.2005.07.004

A review of thymosin beta-4, the full protein from which TB-500 is derived. Summarises its known role in binding actin inside cells and collects animal-model evidence for effects on wound healing, cell migration and cardiac tissue after injury. Concerns the whole protein; findings may not transfer directly to the TB-500 fragment.

review n/a (review)
TB-500

A strong neuroprotective effect of the autonomous C-terminal peptide of IGF-1 Ec (MGF) in brain ischemia

Dluzniewska J, et al. (2005). The FASEB Journal. doi:10.1096/fj.05-3786fje

A preclinical study in gerbils with brain ischemia and in organotypic hippocampal slice cultures. The synthetic C-terminal peptide of IGF-1 Ec (MGF) gave strong protection to ischemic neurons, with an effect that lasted longer than full-length IGF-1 and appeared independent of the IGF-1 receptor. This is an animal and tissue study; it does not test people.

animal gerbil brain ischemia model plus organotypic hippocampal cultures

Mechanisms of vasoactive intestinal peptide-mediated vasodilation in human skin

Wilkins BW, Chung LH, Tublitz NJ, Wong BJ, Minson CT (2004). Journal of Applied Physiology. doi:10.1152/japplphysiol.00366.2004

A physiology study in 43 healthy volunteers using intradermal microdialysis and laser-Doppler flowmetry to work out how VIP dilates skin blood vessels. Across a range of VIP concentrations, blocking nitric oxide synthase reduced the dilation at higher concentrations, blocking H1 histamine receptors reduced it, and blocking both reduced it further, while H2 blockade had no effect. The authors conclude VIP-mediated skin vasodilation involves a nitric-oxide-dependent component not explained by histamine receptors. A mechanistic study, not a treatment trial.

human healthy volunteers, n=43, intradermal microdialysis
VIP (vasoactive intestinal peptide)

Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair

Bock-Marquette I, Saxena A, White MD, et al. (2004). Nature. doi:10.1038/nature03000

The paper that made thymosin beta-4 a subject of regenerative-medicine research. It reported that the peptide promotes migration of heart muscle and blood vessel cells in the embryonic heart and keeps that property in cells from newborn animals, and that it improved survival of heart muscle cells in culture. The authors identified a complex with PINCH and integrin-linked kinase that activates the survival kinase Akt. In mice whose coronary artery had been tied off, treatment raised that kinase activity in the heart, improved early muscle cell survival and improved cardiac function. Note that this concerns the full 43-amino-acid protein, not the shorter TB-500 fragment sold by suppliers.

animal embryonic and postnatal cardiomyocytes in culture, then mice after coronary artery ligation
TB-500

Epithalon Peptide Induces Telomerase Activity and Telomere Elongation in Human Somatic Cells

Khavinson VK, Bondarev IE, Butyugov AA (2003). Bulletin of Experimental Biology and Medicine. doi:10.1023/a:1025493705728

The source of the claim most often made for epitalon. Adding the peptide to cultured human fetal fibroblasts, which do not normally produce telomerase, was reported to switch on expression of the enzyme's catalytic subunit, produce telomerase activity and lengthen telomeres. The authors suggest this could extend the lifespan of a cell population and, they speculate, of an organism. A short report on cells in culture from the group that developed the peptide; the leap from cultured fibroblasts to an organism is theirs and is not demonstrated.

in-vitro cultured human fetal fibroblasts, a cell type that does not normally express telomerase
Epitalon

Inhibitory effect of the peptide epitalon on the development of spontaneous mammary tumors in HER-2/neu transgenic mice

Anisimov VN, Khavinson VK, Provinciali M, et al. (2002). International Journal of Cancer. doi:10.1002/ijc.10570

Female mice genetically engineered to develop mammary tumours were given epitalon, a comparison peptide (vilon) or saline in monthly courses from two months of age. Epitalon-treated mice developed fewer tumours overall and smaller ones, with smaller lung metastases, and HER-2/neu gene expression in their tumours was several times lower than in controls. The comparison peptide had the opposite effect, increasing tumour incidence and shortening the time to tumour appearance. An animal study in a strain bred to develop cancer; the contrast between two similar short peptides is the striking part.

animal female HER-2/neu transgenic mice, treated monthly from 2 months of age, against saline and a comparison peptide
Epitalon

Immunomodulatory synthetic dipeptide L-Glu-L-Trp slows down aging and inhibits spontaneous carcinogenesis in rats

Anisimov VN, Khavinson VK, Morozov VG (2000). Biogerontology. doi:10.1023/A:1010042008969

Seventy-six five-month-old female rats were divided into two groups and injected with either saline or the dipeptide Glu-Trp (the active component of Thymogen) five times a week for a year, then observed until natural death with tumours examined microscopically. Mean lifespan was similar between groups, but the lifespan of the longest-lived 10% was greater in the treated group, the calculated ageing rate was lower, and total and malignant tumour incidence were about 1.5 to 1.7 times lower. A single rat study from the group that developed the compound.

animal female outbred rats, n=76, followed to natural death
Thymogen

Ipamorelin, the first selective growth hormone secretagogue

Raun K, Hansen BS, Johansen NL, et al. (1998). European Journal of Endocrinology. doi:10.1530/eje.0.1390552

The original characterisation of ipamorelin by its developers. In cell and animal models it prompted growth hormone release with little measured effect on cortisol or prolactin, which the authors contrasted with earlier secretagogues. A pharmacology paper from the company that developed the compound.

animal rat pituitary cells, rats, pigs
Ipamorelin

Effects of long-term growth hormone releasing hormone 1-29 in significantly short children

Grunt JA, Schwartz ID, Buchanan C, Howard CP (1995). Acta Paediatrica. doi:10.1111/j.1651-2227.1995.tb13715.x

Seven children who were significantly short but had normal growth hormone levels were treated with GHRH(1-29), with treatment stopped if growth did not improve by a set margin. It was stopped in two children after 12 months and continued in the other five to 24 months. The authors conclude that some children with idiopathic short stature grow well over the first two years of treatment. Seven children, no control group, and a design that drops non-responders, so it shows what happened to those who responded rather than how often a response occurs.

human 7 children with idiopathic short stature and normal growth hormone levels, treated up to 24 months
Sermorelin

Growth response to growth hormone-releasing hormone(1-29)-NH2 compared with growth hormone

Neyzi O, Yordam N, Ocal G, et al. (1993). Acta Paediatrica. doi:10.1111/j.1651-2227.1993.tb12828.x

Forty-three children with growth hormone deficiency originating in the hypothalamus were randomly assigned to lower-dose GHRH(1-29), higher-dose GHRH(1-29), or growth hormone itself, for six months. Height velocity increased by at least 2 cm a year in all but two children. The lower-dose group grew least; the higher-dose GHRH group and the growth hormone group were comparable on height velocity, but only the growth hormone group gained height relative to bone age. The study is from the programme that led to the peptide being marketed for paediatric growth hormone deficiency.

human 43 prepubertal children aged 4 to 19 with growth hormone deficiency of hypothalamic origin, randomised to three treatment groups for 6 months
Sermorelin

Pharmacokinetics of growth hormone-releasing hormone(1-29)-NH2 and stimulation of growth hormone secretion in healthy subjects after intravenous or intranasal administration

Wilton P, Chardet Y, Danielson K, et al. (1993). Acta Paediatrica. doi:10.1111/j.1651-2227.1993.tb12827.x

A pharmacokinetic study in 30 healthy men establishing what the peptide does to growth hormone release and how long it lasts. Intravenous administration produced a measurable growth hormone release even at the lowest amount tested, with the response reaching a ceiling above a certain level; the peptide itself cleared quickly while growth hormone stayed elevated for about three hours. Absorbed through the nose, only 3 to 5 percent reached the bloodstream, so a far larger nasal amount was needed for the same effect. Healthy volunteers, single administrations.

human 30 healthy men aged 19 to 43, intravenous and intranasal administration
Sermorelin

In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds

Maquart FX, Bellon G, Chaqour B, et al. (1993). Journal of Clinical Investigation. doi:10.1172/JCI116842

The animal study behind the collagen claims made for this peptide. Wire mesh chambers were implanted under the skin of rats and injected repeatedly with either GHK-Cu at various concentrations or saline. The contents were then analysed for dry weight, total protein, collagen, DNA, elastin, glycosaminoglycans and specific messenger RNAs. The authors report that the copper complex stimulated accumulation of connective tissue, supporting laboratory findings that had suggested it could activate wound repair. A rat study from 1993; it is the primary source most later reviews rest on.

animal rats with wound chambers implanted under the skin, given repeated injections of GHK-Cu or saline
GHK-Cu

Vasoactive intestinal peptide as a laboratory supplement to clinical activity index in inflammatory bowel disease

Duffy LC, Zielezny MA, Riepenhoff-Talty M, et al. (1989). Digestive Diseases and Sciences. doi:10.1007/BF01537105

Measured circulating VIP by radioimmunoassay in 115 adults with inflammatory bowel disease, studied cross-sectionally and over six months. Plasma VIP was positively associated with clinical disease activity at baseline and follow-up, and roughly doubled during active periods in patients whose disease fluctuated. As a diagnostic marker its sensitivity was about 81% and specificity about 55%. An older observational study of VIP as a marker of disease activity; no peptide was given to patients.

human adults with inflammatory bowel disease, n=115 (48 ulcerative colitis, 67 Crohn's), observational over six months
VIP (vasoactive intestinal peptide)