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.

98 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 Not yet peer reviewed.

preprint (not peer-reviewed) aged C57BL/6J mice (20–21 months), both sexes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

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

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

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

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

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). doi:

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

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

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

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)