Research library
The research library
Every primary source behind a claim on this site, tier-graded for provenance and tagged for the strength of the evidence it carries.
- Sources indexed
- 221
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- 54%
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Reset allT1·Peer-primary literature
Randomized trials, peer-reviewed primary studies, and meta-analyses — the load-bearing layer of the corpus.
61 sources
- 2026Meta-analysismoderaten=1,593,554
Glucagon-like Peptide-1 Receptor Agonists and Risk of Nonarteritic Anterior Ischemic Optic Neuropathy: Systematic Review and Meta-Analysis
Dhivagaran T, Butt F, Arunasalam L, +3 · Neurology
Across 1,593,554 patients in a Neurology-published meta-analysis (682,456 semaglutide users vs 911,098 non-GLP-1RA users), semaglutide use was associated with a 2.5-fold increased risk of nonarteritic anterior ischemic optic neuropathy (RR 2.52; 95% CrI 1.56–4.72), with the strongest signal in patients with diabetes (RR 2.41; 95% CrI 1.57–4.10) — the strongest meta-analytic confirmation to date that the NAION safety signal is real.
- 2026RCTmoderaten=72
Semaglutide and Effort-Based Decision-Making in Major Depressive Disorder: A Randomized Clinical Trial
Gill H, Badulescu S, Shah H, +3 · JAMA Psychiatry
Across 72 adults with major depressive disorder and BMI ≥25, 16 weeks of adjunctive oral semaglutide (14 mg) significantly reduced the perceived cost of effort relative to monetary reward on the Effort-Expenditure for Rewards Task — the first RCT to show GLP-1RA modulation of reward-related motivation in clinical depression.
- 2026Meta-analysismoderate
Effect of Incretin-Based and Nonpharmacologic Weight Loss on Body Composition: A Systematic Review
Batsis JA, Gavras A, Gross DC, +3 · Annals of Internal Medicine
Annals of Internal Medicine systematic review of 36 randomised controlled trials of liraglutide, semaglutide, tirzepatide, and dulaglutide in adults with obesity, evaluating fat mass, fat-free mass, lean soft tissue, and visceral adiposity outcomes against prespecified benchmarks — the most rigorous synthesis to date of the lean-mass concern that has dominated public discourse about incretin therapy.
- 2026RCTmoderaten=204
Liraglutide in mild to moderate Alzheimer's disease: a phase 2b clinical trial
Edison P, Hooper N, Femminella GD, +7 · Nature Medicine
The ELAD Phase 2b in 204 non-diabetic adults with mild-to-moderate Alzheimer's disease missed its primary endpoint of cerebral glucose metabolic rate (p=0.14) — but secondary endpoints reported nearly 50% reduction in brain atrophy and 18% slower ADAS-Exec decline, the secondary-positive signal that handed the question to the larger semaglutide EVOKE Phase 3.
- 2026Mechanisticmoderate
GIPR:GCGR co-agonism restores normal weight in obese rodents
Perez-Tilve D, Zhang F, Zhang Y, +6 · Molecular Metabolism
BWB3054, a dual GIPR:GCGR co-agonist designed to attenuate GLP-1R signalling >100-fold, normalised body weight in diet-induced obese mice and rats and matched retatrutide's weight effect — including in GLP-1R-knockout mice — suggesting the GIP and glucagon arms of the triple-agonist can deliver the bulk of the obesity effect without GLP-1R-driven gastrointestinal liability.
- 2026RCTmoderaten=108
Once-weekly semaglutide versus placebo in patients with alcohol use disorder and comorbid obesity: a randomised, double-blind, placebo-controlled trial
Klausen MK, Justesen SK, Pedersen JN, +3 · The Lancet
Across 108 treatment-seeking adults with alcohol use disorder and comorbid obesity, 26 weeks of once-weekly semaglutide reduced heavy drinking days by −41.1 percentage points from baseline versus −26.4 in placebo — a 13.7-point between-group difference (p=0.0015), the first Lancet-tier RCT confirming a GLP-1RA effect on alcohol consumption.
- 2026Cohortmoderaten=63,083
Risk of Heart Failure Hospitalization for GLP-1 Receptor Agonists Versus DPP-4 Inhibitors or SGLT-2 Inhibitors in Patients With Type 2 Diabetes: A Target Trial Emulation
Xu Y, Huang T, Zhang Y, +4 · Circulation
In a Stockholm 2010–2021 target-trial emulation of 63,083 adults with type 2 diabetes, GLP-1 receptor agonists reduced 3-year heart-failure hospitalization versus DPP-4 inhibitors (HR 0.77; 95% CI 0.66–0.91) but were not different from SGLT-2 inhibitors (HR 1.02; 95% CI 0.85–1.18) — the cleanest comparative-effectiveness signal to date that the GLP-1RA cardioprotective effect is real against DPP-4i but does not match SGLT-2i for the heart-failure endpoint.
- 2025Cohortmoderaten=3,737
GLP-1 Analog Use is Associated With Improved Disease Course in Inflammatory Bowel Disease: A Report from the Epi-IIRN
Gorelik Y, Ghersin I, Lujan R, +9 · Journal of Crohn's and Colitis
In 3,737 patients with IBD and type 2 diabetes drawn from the Israeli Epi-IIRN nationwide cohort, GLP-1-analog use was associated with reduced composite poor IBD outcomes (adjusted HR 0.74) — and the protective signal was carried specifically by the obese subgroup (aHR 0.61), with no detectable effect in non-obese patients.
- 2025Cohortmoderaten=224
GLP-1 Receptor Agonists Confer No Increased Rates of IBD Exacerbation Among Patients With IBD
Levine I, Sekhri S, Schreiber-Stainthorp W, +6 · Inflammatory Bowel Diseases
Among 224 IBD patients prescribed GLP-1 receptor agonists at a large US academic health network between 2009 and 2023, twelve-month rates of IBD exacerbation, IBD-related hospitalization, corticosteroid use, medication escalation, and surgery did not differ from pre-prescription baseline — a null safety signal that independently corroborates the Israeli Epi-IIRN findings.
- 2024RCTmoderaten=3,533
Effects of semaglutide with and without concomitant SGLT2 inhibitor use in participants with type 2 diabetes and chronic kidney disease in the FLOW trial
Mann JFE, Rossing P, Bakris G, +9 · Nature Medicine
Among the 550 FLOW participants on baseline SGLT2 inhibitors, the primary outcome HR was 1.07 (P=0.755); among the 2,983 not on SGLT2 inhibitors it was 0.73 (P<0.001) — a P for interaction of 0.109 that is consistent with underpowered subgroup analysis rather than negative interaction, but leaves the formal stacking question incomplete.
- 2024RCTmoderaten=105
Cagrilintide is not associated with clinically relevant QTc prolongation: A thorough QT study in healthy participants
Gabe MBN, Fuhr R, Sinn A, +5 · Diabetes, Obesity and Metabolism
The thorough-QT study that cleared cagrilintide at the 4.5 mg dose for cardiac repolarisation safety — the regulatory-grade ECG study that closes the QT-prolongation question Phase 3 trials cannot answer at their resolution.
- 2024RCTmoderaten=156
Trial of Lixisenatide in Early Parkinson's Disease
Meissner WG, Remy P, Giordana C, +7 · New England Journal of Medicine
Lixisenatide-treated patients showed no motor decline at 12 months while placebo-treated patients worsened by 3.04 MDS-UPDRS-III points — a 3.08-point between-group separation (p=0.0068) that is the first positive primary endpoint for a GLP-1 agonist in early Parkinson's disease.
- 2024RCTmoderaten=176
ReCLAIM-2: A Randomized Phase II Clinical Trial Evaluating Elamipretide in Age-related Macular Degeneration, Geographic Atrophy Growth, Visual Function, and Ellipsoid Zone Preservation
Ehlers JP, Hu A, Boyer D, +4 · Ophthalmology Science
Across 176 patients with dry age-related macular degeneration and geographic atrophy, ReCLAIM-2 missed both prespecified primary endpoints — low-luminance visual acuity and GA area progression — but produced statistically significant secondary signals on ellipsoid zone preservation (43% reduction in total EZ attenuation, p = 0.0034) that Stealth has cited as proof-of-mechanism for future development.
- 2024RCTmoderaten=413
Dose-response effects on HbA1c and bodyweight reduction of survodutide, a dual glucagon/GLP-1 receptor agonist, compared with placebo and open-label semaglutide in people with type 2 diabetes: a randomised clinical trial
Blüher M, Rosenstock J, Hoefler J, +2 · Diabetologia
Survodutide doses ≥1.8 mg achieved greater body-weight reduction than open-label semaglutide 1.0 mg (-5.3% to -8.7% vs -5.3%) at 16 weeks while matching HbA1c reductions — a short-window signal that motivated the Phase 3 program in obesity and T2D.
- 2023RCTmoderaten=92
Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial
Frias JP, Deenadayalan S, Erichsen L, +6 · Lancet
The Phase 2 type 2 diabetes trial that established CagriSema's combination signal in a diabetic cohort — 15.6% weight loss and 2.2-percentage-point HbA1c reduction at 32 weeks on CagriSema versus 5.1% / 1.8% on semaglutide alone, in 92 adults on metformin background. The cohort was small but it set the framing under which REDEFINE-2 was designed.
- 2022Case reportmoderaten=17
Peripheral Neuropathy Evaluations of Patients With Prolonged Long COVID
Oaklander AL, Mills AJ, Kelley M, +4 · Neurology - Neuroimmunology & Neuroinflammation
A 17-patient referred case series — 59% with at least one confirmatory neuropathy test, 63% with abnormal skin biopsies, and at least 10 receiving small-fiber neuropathy diagnoses — the pivotal characterisation paper establishing small-fiber neuropathy as a measurable, biopsy-confirmable component of long COVID.
- 2021Mechanisticmoderaten=49
Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin
Pretorius E, Vlok M, Venter C, +4 · Cardiovascular Diabetology
The foundational microclot-in-PASC observation paper — fluorescent staining and proteomics on plasma from 11 PASC patients identified amyloid fibrin deposits resistant to trypsin-mediated fibrinolysis, with α2-antiplasmin elevated approximately eightfold within the resistant pellet versus healthy controls.
- 2021RCTmoderaten=96
Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial
Enebo LB, Berthelsen KK, Kankam M, +4 · Lancet
The Phase 1b dose-escalation study that established cagrilintide's once-weekly pharmacokinetic profile (half-life 159–195 hours) and produced the first human signal that combination amylin + GLP-1 agonism could exceed semaglutide monotherapy — 17.1% weight loss at week 20 on cagrilintide 2.4 mg plus semaglutide 2.4 mg, all in 96 healthy-overweight adults at a single US site.
- 2021RCTmoderaten=12
A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome, a genetic disorder of mitochondrial cardiolipin metabolism
Thompson WR, Hornby B, Manuel R, +4 · Genetics in Medicine
Across 12 subjects with genetically confirmed Barth syndrome, the randomized 12-week crossover period missed both primary endpoints, but the 36-week open-label extension produced a 95.9-metre improvement in six-minute walk distance and meaningful gains in patient-reported and strength endpoints — the foundational efficacy dataset behind the September 2025 FDA approval of Forzinity for Barth syndrome.
- 2021Mechanisticmoderaten=224
Immune-Based Prediction of COVID-19 Severity and Chronicity Decoded Using Machine Learning
Patterson BK, Guevara-Coto J, Yogendra R, +7 · Frontiers in Immunology
A 224-individual immune-profiling study that documented PASC-distinctive elevations in CCL5/RANTES, IL-2, IL-4, CCL3, IL-6, IL-10, IFN-γ, and VEGF alongside expanded CD14+/CD16+/CCR5+ monocyte subsets — the most-cited immune-signature characterisation in the early PASC literature, and structurally separate from the same group's subsequent treatment claims.
- 2019Cohortmoderaten=684
Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder
Simon JA, Kingsberg SA, Portman D, +5 · Obstetrics and Gynecology
52-week open-label extension of the RECONNECT phase-3 trials — 684 women received bremelanotide for up to 76 weeks total, with nausea (40.4%), flushing (20.6%), and headache (12.0%) the most common adverse events and no new safety signals beyond the on-demand-use profile already established in the core trials.
- 2018RCTmoderaten=36
Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy
Karaa A, Haas R, Goldstein A, +3 · Neurology
Across 36 adults with genetically confirmed primary mitochondrial myopathy, the highest-dose elamipretide arm walked 64.5 metres farther on the six-minute walk test at day 5 versus 20.4 metres on placebo — the positive Phase 2 signal that motivated the larger MMPOWER-3 trial that ultimately failed.
- 2018Mechanisticmoderate
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, +5 · Biochemical Pharmacology
Eleven days of subcutaneous 5-Amino-1MQ at 20 mg/kg three times daily produced approximately 5% body weight loss and a roughly 35% reduction in epididymal white adipose tissue mass in diet-induced-obese mice — the pharmacological replication of the Kraus 2014 antisense-knockdown phenotype that anchors every subsequent NNMT-inhibitor claim.
- 2017RCTmoderaten=44
Novel Mitochondria-Targeting Peptide in Heart Failure Treatment: A Randomized, Placebo-Controlled Trial of Elamipretide
Daubert MA, Yow E, Dunn G, +7 · Circulation Heart Failure
A single high-dose elamipretide infusion produced acute reductions in left ventricular end-diastolic (−18 mL) and end-systolic (−14 mL) volume versus placebo in 44 stable heart-failure patients — the early signal that motivated the PROGRESS-HF Phase 2 trial, which then failed to confirm chronic-dosing benefit at 4 weeks.
- 2017Mechanisticmoderate
GABA, Selank, and Olanzapine Affect the Expression of Genes Involved in GABAergic Neurotransmission in IMR-32 Cells
Filatova E, Kasian A, Kolomin T, +8 · Frontiers in Pharmacology
Selank alone produced no change in GABAergic gene expression in IMR-32 cells; the effect appeared only in combination with GABA or olanzapine — the cleanest Western-indexed mechanism paper showing Selank as a co-modulator rather than a primary releaser.
- 2017RCTmoderaten=29
Kisspeptin modulates sexual and emotional brain processing in humans
Comninos AN, Wall MB, Demetriou L, +24 · Journal of Clinical Investigation
Kisspeptin-54 enhanced limbic-brain responses to sexual and couple-bonding stimuli and attenuated negative mood in a placebo-controlled crossover fMRI study — the first human evidence linking the hypothalamic reproductive switch to the brain's affective circuitry.
- 2016RCTmoderaten=208
Cerebrolysin and Recovery After Stroke (CARS): A Randomized, Placebo-Controlled, Double-Blind, Multicenter Trial
Muresanu DF, Heiss WD, Hoemberg V, +8 · Stroke
CARS-1 is the Cerebrolysin trial in which the protocol was tightest, the rehabilitation co-intervention was standardized, and the primary endpoint — upper-extremity motor recovery on the Action Research Arm Test at day 90 — favored Cerebrolysin with a Mann-Whitney effect size of 0.71 (95% CI 0.63–0.79, P<0.0001).
- 2015RCTmoderaten=9
Thymosin β4 significantly improves signs and symptoms of severe dry eye in a phase 2 randomized trial
Sosne G, Dunn SP, Kim C · Cornea
In a 9-patient Phase 2 dry eye trial, 0.1% thymosin β4 ophthalmic solution reduced ocular discomfort by 35.1% and corneal fluorescein staining by 59.1% versus vehicle control — small but the cleanest published signal that the cardiac-mechanism literature on thymosin β4 might translate clinically.
- 2015RCTmoderaten=72
Thymosin beta 4 ophthalmic solution for dry eye: a randomized, placebo-controlled, Phase II clinical trial conducted using the controlled adverse environment (CAE) model
Sosne G, Ousler GW · Clinical Ophthalmology
A 72-subject Phase 2 dry-eye RCT of 0.1% thymosin β4 ophthalmic solution: the formal primary endpoints did not separate from placebo, but treated subjects showed a 27% reduction in discomfort during controlled adverse environment exposure and statistically significant improvements in corneal staining — the larger companion to the Sosne 2015 Cornea trial.
- 2015RCTmoderaten=342
Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial
Leffler DA, Kelly CP, Green PHR, +8 · Gastroenterology
Larazotide acetate at 0.5 mg three times daily improved celiac-disease symptom scores versus placebo (ANCOVA p=0.022) in adults with persistent symptoms despite a gluten-free diet — the Phase IIb signal that licensed an attempt at registration that the Phase 3 program failed to confirm in 2022.
- 2014RCTmoderaten=114
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 · International Journal of Colorectal Disease
Median time to first tolerated meal was 25.3 hours with ipamorelin versus 32.6 hours with placebo — a seven-hour edge in the expected direction, but p = 0.15, and the rigorous indication trial that should have made ipamorelin a prescription drug fell short of statistical significance.
- 2014RCTmoderaten=50
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, +4 · JAMA
First randomized trial to demonstrate that tesamorelin reduces liver fat — not just visceral fat — in HIV-infected adults with abdominal fat accumulation, opening the door to the NAFLD line of investigation that the Grinspoon group has pursued since.
- 2013Mechanisticmoderate
Evaluation of metabolically stabilized angiotensin IV analogs as procognitive/antidementia agents
McCoy AT, Benoist CC, Wright JW, +6 · Journal of Pharmacology and Experimental Therapeutics
Dihexa restored cognitive performance in scopolamine-impaired and aged rats, distributed effectively to brain after oral administration, and produced marked synaptogenic activity in hippocampal cultures — the foundational paper for everything that followed.
- 2013RCTmoderaten=48
ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density
Dahan A, Dunne A, Swartjes M, +9 · Molecular Medicine
Twenty-eight days of daily subcutaneous cibinetide in sarcoidosis patients with documented small-nerve-fiber loss produced a significant increase in corneal small-nerve-fiber density, improved thermal sensitivity, and increased exercise capacity — the trial that anchored the move from a pilot signal to a structurally defensible Phase II readout.
- 2012RCTmoderaten=60
Metabolic Effects of a Growth Hormone-Releasing Factor in Obese Subjects with Reduced Growth Hormone Secretion: A Randomized Controlled Trial
Makimura H, Feldpausch MN, Rope AM, +4 · Journal of Clinical Endocrinology and Metabolism
Twelve months of tesamorelin in non-HIV abdominally obese adults with reduced GH secretion selectively reduced visceral adipose tissue without affecting subcutaneous fat, improved triglycerides and carotid intima-media thickness, and preserved glucose tolerance — the cleanest non-HIV reading of tesamorelin's metabolic effect available.
- 2012Cohortmoderaten=402
Reduction in visceral adiposity is associated with an improved metabolic profile in HIV-infected patients receiving tesamorelin
Stanley TL, Falutz J, Marsolais C, +6 · Clinical Infectious Diseases
Among 402 tesamorelin-treated HIV patients, the visceral-fat responders (>=8% VAT reduction) showed dramatically better triglycerides, fasting glucose, and adiponectin than nonresponders at both 26 and 52 weeks — establishing that the metabolic benefit follows the body-composition response.
- 2012RCTmoderaten=22
Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study
Heij L, Niesters M, Swartjes M, +8 · Molecular Medicine
Twelve patients on ARA-290 versus ten on placebo, intravenous 2 mg three times weekly for four weeks — and a statistically significant improvement in the Small Fiber Neuropathy Screening List score versus placebo at week 4. The first human trial of cibinetide in sarcoidosis-associated small-fiber neuropathy.
- 2011RCTmoderaten=123
MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: A multicenter, randomized, placebo-controlled phase IIb study
Adunsky A, Chandler J, Heyden N, +5 · Archives of Gerontology and Geriatrics
IGF-1 rose, gait speed improved modestly (p=0.011), most functional measures did not differentiate — and the trial was terminated early on a congestive heart failure signal (4 of 62 active-arm versus 1 of 61 placebo-arm patients). The MK-677 sarcopenia-adjacent reading that reproduced the Nass mass-without-function pattern with a safety signal attached.
- 2010RCTmoderaten=40
A randomized, placebo-controlled, single and multiple dose study of intravenous thymosin beta4 in healthy volunteers
Ruff D, Crockford D, Girardi G, +1 · Annals of the New York Academy of Sciences
The Phase 1 human-safety paper that gated everything downstream: 40 healthy volunteers received IV thymosin β4 at 42, 140, 420, or 1260 mg single doses then daily for 14 days, with no dose-limiting toxicities, no serious adverse events, and a dose-proportional PK profile.
- 2010Mechanisticmoderate
Cardioprotection by a nonerythropoietic, tissue-protective peptide mimicking the 3D structure of erythropoietin
Ueba H, Brines M, Yamin M, +5 · PNAS
The 11-amino-acid helix B surface peptide that became ARA-290 inhibits TNF-α-induced cardiomyocyte apoptosis by approximately 80% and reduces in-vivo cardiac apoptosis by approximately 70% in a hamster dilated-cardiomyopathy model — extending the IRR mechanism into a cardiac-protection indication that did not progress to clinical development.
- 2008Mechanisticmoderate
PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation
Dalmasso G, Charrier-Hisamuddin L, Nguyen HTT, +3 · Gastroenterology
KPV enters epithelial and immune cells through PepT1, suppresses NF-κB at nanomolar concentrations, and reduces colitis severity in two independent mouse models — the foundational paper for the entire current case for KPV in inflammatory bowel disease.
- 2008Mechanisticmoderate
Pentadecapeptide BPC 157, in clinical trials as a therapy for inflammatory bowel disease (PL14736), is effective in the healing of colocutaneous fistulas in rats: role of the nitric oxide-system
Klicek R, Sever M, Radic B, +17 · Journal of Pharmacological Sciences
BPC-157 accelerated closure of colon-to-skin fistulas in rats whether given by injection or orally; corticosteroids — the conventional comparator — worsened healing.
- 2008RCTmoderaten=62
Efficacy and possible mechanisms of action of a new peptide anxiolytic Selank in the therapy of generalized anxiety disorders and neurasthenia
Zozulia AA, Neznamov GG, Siuniakov TS, +11 · Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova
Across 62 patients with GAD or neurasthenia, Selank's anxiolytic effect was reported as comparable to medazepam — the only English-indexed clinical trial that puts Selank head-to-head against a benzodiazepine.
- 2008Mechanisticmoderate
Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease
Kannengiesser K, Maaser C, Heidemann J, +7 · Inflammatory Bowel Diseases
KPV given orally rescued every animal in the MC1Re/e DSS-colitis arm from death — demonstrating that the tripeptide's anti-inflammatory activity does not require a functional melanocortin-1 receptor and runs in parallel to the Dalmasso PepT1-transport mechanism.
- 2007Mechanisticmoderate
Thymosin beta4 induces adult epicardial progenitor mobilization and neovascularization
Smart N, Risebro CA, Melville AAD, +4 · Nature
Thymosin β4 stimulated outgrowth from quiescent adult epicardial explants, restoring pluripotency and triggering differentiation into fibroblasts, smooth muscle cells, and endothelial cells — the second foundational Nature paper that drove the cardiac-repair clinical-development arc.
- 2007Mechanisticmoderate
Non-clinical pharmacology and safety evaluation of TH9507, a human growth hormone-releasing factor analogue
Ferdinandi ES, Brazeau P, High K, +3 · Basic and Clinical Pharmacology & Toxicology
The preclinical design and characterization paper for tesamorelin — TH9507's hexenoyl modification of native GHRH conferred DPP-IV resistance and a 21–45 minute half-life in dogs, the engineering moves that enabled the clinical-trial program.
- 2006Mechanisticmoderaten=8
Pulsatile Secretion of Growth Hormone (GH) Persists during Continuous Stimulation by CJC-1295, a Long-Acting GH-Releasing Hormone Analog
Ionescu M, Frohman LA · Journal of Clinical Endocrinology & Metabolism
After a single subcutaneous dose, CJC-1295 elevated trough GH by 7.5-fold and IGF-I by 45% while leaving the frequency and amplitude of GH pulses unchanged — a continuous GHRH signal that does not flatten physiological pulsatility.
- 2006Mechanisticmoderate
Achilles detachment in rat and stable gastric pentadecapeptide BPC 157: promoted tendon-to-bone healing and opposed corticosteroid aggravation
Krivic A, Anic T, Seiwerth S, +2 · Journal of Orthopaedic Research
Tendon-to-bone — a tissue interface that does not heal spontaneously after sharp transection in rats — was functionally and biomechanically restored by intraperitoneal BPC-157, including in animals concurrently treated with corticosteroids that worsened healing alone.
- 2005Mechanisticmoderate
Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents
Eremin KO, Kudrin VS, Saransaari P, +4 · Neurochemical Research
Semax did not move dopamine on its own, but pretreatment dramatically enhanced amphetamine-induced dopamine release — a neuromodulatory amplifier rather than a primary releaser.
- 2004Mechanisticmoderate
Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair
Bock-Marquette I, Saxena A, White MD, +2 · Nature
Thymosin β4 promoted myocyte migration and survival through an integrin-linked-kinase / Akt pathway and improved cardiac function in mice after coronary artery ligation — the mechanistic foundation for everything that followed in the cardiac-repair literature.
- 2003Mechanisticmoderate
Epithalon peptide induces telomerase activity and telomere elongation in human somatic cells
Khavinson VKh, Bondarev IE, Butyugov AA · Bulletin of Experimental Biology and Medicine
In telomerase-negative human fetal fibroblasts, Epithalon induced expression of the telomerase catalytic subunit, enzymatic activity, and telomere elongation — the foundational mechanistic claim that anchors the entire modern Epitalon literature.
- 2002Cohortmoderaten=80
Inhibitory effect of peptide Epitalon on colon carcinogenesis induced by 1,2-dimethylhydrazine in rats
Anisimov VN, Khavinson VKh, Popovich IG, +1 · Cancer Letters
The Khavinson-group cancer-prevention companion to their longevity work — 80 male LIO rats, DMH-induced colon carcinogenesis model, 1 microgram Epitalon five days a week for 6 months. Total colon tumors per rat fell from 4.1 (control) to 2.7 (continuous Epitalon) and 2.9 (Epitalon during DMH exposure only); the post-DMH-only arm at 3.7 did not reach significance. Continuous-exposure arm also showed significantly decreased tumor incidence and multiplicity in ascending and descending colon and inhibition of tumor development in jejunum and ileum.
- 2001Cohortmoderaten=150
Effect of synthetic thymic and pineal peptides on biomarkers of ageing, survival and spontaneous tumour incidence in female CBA mice
Anisimov VN, Khavinson VKh, Mikhalski AI, +1 · Mechanisms of Ageing and Development
The Khavinson group's central long-term-dosing animal study supporting geroprotective claims for Vilon (Lys-Glu thymic dipeptide) and Epitalon (Ala-Glu-Asp-Gly pineal tetrapeptide) — 50 female CBA mice per arm, lifelong monthly dosing from 6 months of age, +5.3% mean survival on Epitalon (p<0.05) and decreased lung-adenoma incidence on both peptides.
- 2001Mechanisticmoderate
The Effects of Human GH and Its Lipolytic Fragment (AOD9604) on Lipid Metabolism Following Chronic Treatment in Obese Mice and β3-AR Knock-Out Mice
Heffernan M, Summers RJ, Thorburn A, +4 · Endocrinology
Both hGH and AOD-9604 upregulated β3-adrenergic-receptor expression and produced weight loss in obese wild-type mice, but neither compound sustained those effects in β3-AR knockout animals — the experiment that localised AOD-9604's lipolytic mechanism to the β3 channel.
- 2000Mechanisticmoderate
Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone
Ng FM, Sun J, Sharma L, +3 · Hormone Research
Nineteen days of oral 500 µg/kg/day AOD-9604 in obese Zucker rats reduced body-weight gain by more than half versus control (15.8 vs. 35.6 g), increased ex vivo adipose lipolytic activity, and produced no detectable insulin-sensitivity decrement under euglycemic clamp — the foundational preclinical paper for the molecule.
- 1998RCTmoderaten=12
Growth hormone status during long-term hexarelin therapy
Rahim A, O'Neill PA, Shalet SM · Journal of Clinical Endocrinology & Metabolism
Sixteen weeks of twice-daily subcutaneous hexarelin in elderly subjects: mean GH AUC fell from 19.1 µg/L/h at baseline to 13.1 at week 1, 12.3 at week 4, and 10.5 at week 16 — a roughly 45% loss of the GH response, reversible after four weeks of washout. The receptor-desensitisation paper that grounds modern hexarelin cycling logic.
- 1998RCTmoderaten=8
MK-677, an Orally Active Growth Hormone Secretagogue, Reverses Diet-Induced Catabolism
Murphy MG, Plunkett LM, Gertz BJ, +4 · Journal of Clinical Endocrinology & Metabolism
In an 8-volunteer crossover trial, oral MK-677 (25 mg daily) reversed nitrogen wasting induced by 14 days of caloric restriction — the first published human evidence that an orally bioavailable ghrelin-mimetic could produce a clinically meaningful anabolic signal.
- 1997RCTmoderaten=19
Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women
Khorram O, Laughlin GA, Yen SS · Journal of Clinical Endocrinology & Metabolism
Nineteen healthy adults aged 55–71 received nightly subcutaneous [Nle27]GHRH(1-29)-NH2 at 10 µg/kg or placebo for five months. Nocturnal GH and IGF-1 rose, lean-body-mass effects appeared in men, skin thickness rose in women — the load-bearing controlled adult sermorelin-analog trial whose modest scale defines the evidence ceiling for adult GHRH-axis modulation.
- 1997RCTmoderaten=11
Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men
Vittone J, Blackman MR, Busby-Whitehead J, +10 · Metabolism
Eleven healthy older men aged 64–76 received a single nightly subcutaneous GHRH(1-29) dose of 2 mg for six weeks. Nocturnal GH release rose and isolated muscle-strength measures improved, but IGF-1, body weight, DEXA body composition, glucose, insulin, and lipids did not change — the trial that established single-nightly dosing as less effective than multiple-daily regimens.
- 1996RCTmoderaten=33
A randomized controlled trial of thymosin-alpha1 versus interferon alfa treatment in patients with hepatitis B e antigen antibody-- and hepatitis B virus DNA--positive chronic hepatitis B
Andreone P, Cursaro C, Gramenzi A, +9 · Hepatology
In a 33-patient head-to-head comparison, thymosin-α1 produced a similar response rate to interferon alfa in anti-HBe-positive chronic hepatitis B at end-of-treatment and a higher complete response rate at six-month follow-up — the comparator-grade evidence that anchored thymosin-α1's hepatitis B regulatory record.
- 1978Mechanisticmoderate
The delta EEG (sleep)-inducing peptide (DSIP). XI. Amino-acid analysis, sequence, synthesis and activity of the nonapeptide
Schoenenberger GA, Maier PF, Tobler HJ, +2 · Pflügers Archiv
Synthetic DSIP, given to recipient rabbits, reproduced the original blood-fraction's delta- and spindle-EEG-enhancing activity — a 35% delta-power increase in neocortex and limbic cortex versus controls.
T2·Peer-secondary literature
Peer-reviewed reviews and cohort/observational work — context, not bedrock.
48 sources
- 2026Mechanisticmoderate
Semaglutide Reverses Ectopic Lipid Accumulation, Impaired Myocardial Perfusion Reserve, and Diastolic Dysfunction in a Mouse Model of Cardiometabolic Heart Disease
Skacel TP, Saleh NR, Pavelec CM, +3 · JACC Basic to Translational Science
In a pair-fed mouse design that isolates weight-independent effects, semaglutide reversed obesity-induced cardiometabolic heart disease — reducing proinflammatory epicardial adipose, ectopic lipid, and myocardial fibrosis, and restoring myocardial perfusion reserve and diastolic strain — while pair-fed controls matched for reduced caloric intake did not.
- 2026Meta-analysismoderaten=25,847
Tirzepatide Beyond Diabetes and Obesity: Systematic Review and Meta-Analysis of Multisystem Therapeutic Benefits
Eisa N, Barood O · Endocrine Practice
A 17-RCT, 25,847-patient meta-analysis pooling tirzepatide's multi-organ outcomes: cardiovascular non-inferiority versus dulaglutide (HR 0.92), 38% reduction in HFpEF death-or-HF-event (HR 0.62), MASH resolution in 62% (RR 5.33), 21.9-event/hour drop in apnea-hypopnea index, 5.8 mm Hg SBP reduction, +1.5 mL/min/year eGFR preservation, and 32.9% hsCRP reduction.
- 2026Cohortmoderaten=347,026
Use of Glucagon-Like Peptide-1 Receptor Agonists and Risk of Parkinson's Disease: Scandinavian Cohort Study
Engström A, Svanström H, Hviid A, +3 · Diabetes, Obesity and Metabolism
Across 158,961 new users of GLP-1 receptor agonists in Denmark, Norway and Sweden — liraglutide-dominant (72.9% of follow-up) — compared with 188,065 new users of sulfonylureas, GLP-1RA use was associated with a 19% lower incidence of Parkinson's disease over follow-up (adjusted HR 0.81; 95% CI 0.68–0.96), with the signal strengthening to HR 0.74 (0.60–0.93) after excluding or censoring DPP-4 inhibitor users.
- 2026Cohortmoderaten=1,183,817
Depressed mood and suicidal thoughts reporting with GLP-1 receptor agonists in type 2 diabetes: A WHO VigiBase study
Aboukaoud M, Hoch B, Weiser M, +1 · Journal of Affective Disorders
Across 1,183,817 GLP-1RA adverse-event reports in the WHO VigiBase pharmacovigilance database, semaglutide, liraglutide and tirzepatide all showed elevated reporting of depressed mood (adjusted ROR0.25: 2.13, 1.52, 1.07) and suicidal thoughts (6.76, 2.43, 3.39) — but with no signal for suicide attempts or completed suicide, and with concomitant antidepressant use and comorbid depression 25–120% higher than in comparator drug users, suggesting affective vulnerability drives the signal rather than a uniform drug-specific effect.
- 2026Cohortmoderaten=36
Semaglutide improves markers of cardiovascular risk in people with HIV
Lake JE, Kitch DW, Kantor A, +3 · AIDS
In the first lipidomic and lipo-/glyco-protein profiling of semaglutide therapy in any population — 36 adults with HIV and MASLD from the SLIM LIVER (ACTG A5371) trial — semaglutide reduced triglycerides, diglycerides, sphingomyelins, and CVD-linked lipoprotein species; 56% with elevated GlycA improved and 32% normalised, with effects independent of changes in weight, liver fat, or insulin resistance.
- 2026Reviewmoderate
Safety and Efficacy of Approved and Unapproved Peptide Therapies for Musculoskeletal Injuries and Athletic Performance
Mendias CL, Awan TM · Sports Medicine
A 2026 Sports Medicine narrative review by the Performance Medicine Institute mapping the pharmacology, safety, and regulatory status of twelve sports-marketed peptides — AOD-9604, BPC-157, CJC-1295, FS-344, GHK-Cu, ipamorelin, MOTS-C, sermorelin, SS-31, tesamorelin, Tβ4, and TB-500 — and the first credible journal-tier framework for clinicians discussing the gray-market peptide channel with patients.
- 2026Cohortmoderaten=348,649
Integrated Evidence from VigiBase and Clinical Trials: A Comprehensive Pharmacovigilance Analysis of Seven Glucagon-Like Peptide 1 Receptor Agonists (GLP-1 RAs)
Li J, Liang J, Zhang W, +2 · Diabetes Therapy
Across 348,649 GLP-1RA adverse-event reports in the WHO VigiBase database through January 2025, the seven approved GLP-1 receptor agonists show distinct drug-level safety signatures — tirzepatide with abdominal pain (ROR025 53.54), liraglutide with drug-ineffective reports (31.14) and pancreatitis (4.24), exenatide with injection-site pain (70.14) — that complicate the simple class-effect framing and inform personalised prescribing.
- 2026Reviewmoderate
Mitochondrial dysfunction-driven inflammation and β-Cell apoptosis in type 2 diabetes mellitus: mechanistic insights and therapeutic implications
Yadav S, Kumar G, Kumar S, +2 · Molecular Biology Reports
Mitochondria-targeted antioxidants MitoQ and SS-31 appear in this 2026 Molecular Biology Reports T2DM review as candidate β-cell-preserving therapeutics, alongside the explicit caveat that poor tissue specificity, poor bioavailability, and patient-to-patient variability remain the dominant translational barriers.
- 2026Reviewmoderate
FDA-Approved Drugs Containing D-Amino Acids: A Historical and Developmental Perspective
Tran L, Nguyen TD, Gad AG, +6 · Drug Development Research
More than twenty FDA-approved drugs incorporate at least one D-amino acid; bremelanotide (PT-141) — the cyclic heptapeptide melanocortin agonist approved for hypoactive sexual desire disorder — is one of them, and the chemistry that made approval possible is the same chemistry the gray-market melanocortin landscape now leans on.
- 2026Cohortmoderaten=228
Computational phenotyping of effort-based decision-making in type-2 diabetes on and off semaglutide
Mehrhof SZ, Fleming H, Nord CL · Neuropsychopharmacology
In a pre-registered Cambridge MRC CBU study, adults with type-2 diabetes (N=112, on or off semaglutide) showed a blunted effort-acceptance bias on a computational decision-making task compared with matched controls (N=116) — a metabolic-cognitive shift toward energy conservation that was not restored by semaglutide treatment and was not driven by neuropsychiatric comorbidity or antidepressant use.
- 2026Reviewmoderate
Incretin-Based Anti-obesity Medications in Polycystic Ovary Syndrome: The Evidence Map
Jensterle M, Janez A · Drugs
Drugs review by the Ljubljana endocrinology group mapping GLP-1RA and dual GIP/GLP-1 RA evidence in polycystic ovary syndrome — liraglutide has the densest PCOS-specific evidence with reproducible weight loss, visceral and hepatic fat reduction, and early signals on androgen and fertility benefits; semaglutide and tirzepatide data remain extrapolative.
- 2026Cohortmoderaten=14,844
Glucagon-Like Peptide-1 Receptor Agonists and Cardiovascular Outcomes in Patients With Atherosclerotic Cardiovascular Disease and Obesity Without Diabetes
Akbar UA, Mondal A, Vorla M, +3 · The American Journal of Cardiology
In a propensity-matched real-world cohort of 14,844 non-diabetic adults with established atherosclerotic cardiovascular disease and BMI ≥27, GLP-1RA initiation was associated with a 32% relative reduction in 5-year all-cause mortality (HR 0.68; 95% CI 0.53-0.88; p=0.003) — extending the SELECT trial signal across multiple GLP-1 agents in real-world practice.
- 2022RCTmoderaten=88
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Positive Modulator of HGF/MET, Fosgonimeton, in Healthy Volunteers and Subjects with Alzheimer's Disease: Randomized, Placebo-Controlled, Double-Blind, Phase I Clinical Trial
Hua X, Church K, Walker W, +5 · Journal of Alzheimer's Disease
First-in-human Phase I trial of fosgonimeton (ATH-1017), the prodrug of the active metabolite ATH-1001 that descends from the Wright/Harding dihexa program — 88 subjects across young healthy, elderly healthy, and Alzheimer's cohorts, with the drug safe and well-tolerated and signals of qEEG gamma-power induction and P300 latency normalization in the AD cohort.
- 2022Meta-analysismoderaten=135,874
Treatment with glucagon-like peptide-1 receptor agonists and incidence of dementia: Data from pooled double-blind randomized controlled trials and nationwide disease and prescription registers
Nørgaard CH, Friedrich S, Hansen CT, +9 · Alzheimer's & Dementia Translational Research & Clinical Interventions
Pooled cardiovascular-outcome trials (n=15,820) reported dementia HR 0.47 (95% CI 0.25–0.86) with GLP-1 RA randomization; the parallel Danish nationwide registry of 120,054 patients returned HR 0.89 per year of GLP-1 RA exposure — the load-bearing observational signal that motivated the EVOKE and ELAD interventional programs.
- 2021Opinionmoderate
The regulatory approval of anamorelin for treatment of cachexia in patients with non-small cell lung cancer, gastric cancer, pancreatic cancer, and colorectal cancer in Japan: facts and numbers
Wakabayashi H, Arai H, Inui A · Journal of Cachexia, Sarcopenia and Muscle
Anamorelin received Japanese PMDA approval on 11 December 2020 for cancer cachexia in four indications — the first regulatory approval for cancer cachexia globally and the first GHSR-1a-agonist approval for a muscle-wasting indication, on essentially the same data the EMA had rejected in 2017.
- 2020Mechanisticmoderate
Predominance of Nootropic or Anxiolytic Effects of Selank, Semax, and Noopept Peptides Depending on the Route of Administration to BALB/c and C57BL/6 Mice
Vasileva EV, Kondrakhin EA, Abdullina AA, +2 · Neurochemical Journal
The Zakusov Institute's mouse-strain replication of the Manchenko 2010 route-dissociation finding, extended to three peptides (Selank, Semax, Noopept) across two routes (i.p. vs i.n.) and two genetic backgrounds (BALB/c, C57BL/6). In BALB/c — but not in C57BL/6 — anxiolytic efficacy is higher after intraperitoneal injection while nootropic efficacy is higher after intranasal administration.
- 2020Reviewmoderate
Thymosin alpha 1: A comprehensive review of the literature
Dominari A, Hathaway D III, Pandav K, +14 · World Journal of Virology
Approved in over 35 countries for hepatitis B and C, with extending use in sepsis, severe infections, vaccine adjunct, and emerging COVID-19 lymphocyte-preservation indications — the deepest cumulative clinical exposure of any peptide on this site.
- 2020Mechanisticmoderate
The mitochondria-targeted peptide SS-31 binds lipid bilayers and modulates surface electrostatics as a key component of its mechanism of action
Mitchell W, Ng EA, Tamucci JD, +9 · Journal of Biological Chemistry
Biophysical and molecular-dynamics analysis showed SS-31 partitions into the membrane interfacial region with affinity proportional to surface charge, does not destabilise bilayer structure, and modulates surface electrostatics — refining the Birk 2013 cardiolipin-binding mechanism into a broader 'membrane electrostatic modulation' framework.
- 2020Cohortmoderaten=76
Thymosin Alpha 1 Reduces the Mortality of Severe Coronavirus Disease 2019 by Restoration of Lymphocytopenia and Reversion of Exhausted T Cells
Liu Y, Pan Y, Hu Z, +13 · Clinical Infectious Diseases
In 76 severe COVID-19 patients across two Wuhan hospitals, thymosin α-1 reduced 28-day mortality from 30.0% to 11.1% — restored CD8+ and CD4+ T-cell counts and reduced PD-1/Tim-3 exhaustion markers, with the largest mortality benefit in patients with the deepest lymphopenia at baseline.
- 2020Cohortmoderaten=104
Increased expression of the mitochondrial derived peptide, MOTS-c, in skeletal muscle of healthy aging men is associated with myofiber composition
D'Souza RF, Woodhead JST, Hedges CP, +8 · Aging
Across 104 healthy men in three age strata, plasma MOTS-c declined 21% from young to elderly cohorts — but skeletal-muscle MOTS-c expression rose 1.5-fold with age and tracked slow-fibre composition, suggesting two distinct tissue-specific regulatory patterns rather than a single age-decline curve.
- 2020Mechanisticmoderate
The effect of pentadecapeptide BPC 157 on hippocampal ischemia/reperfusion injuries in rats
Vukojevic J, Vrdoljak B, Malekinusic D, +8 · Brain and Behavior
The Sikiric Zagreb group's bilateral-carotid-clamp stroke model in Wistar rats: 10 µg/kg BPC 157 applied as a topical 1 mL bath 30 seconds after a 20-minute reperfusion start prevented hippocampal red-neuron death, restored Morris water maze / beam-walk / lateral-push performance, and shifted the NO-synthase gene-expression panel toward the cytoprotective constitutive isoforms (Nos3, Nos1 up; Nos2 down) — the corpus's load-bearing post-2018 mechanistic candidate for BPC-157 in stroke.
- 2018Reviewmoderate
Novel Cytoprotective Mediator, Stable Gastric Pentadecapeptide BPC 157. Vascular Recruitment and Gastrointestinal Tract Healing
Sikiric P, Rucman R, Turkovic B, +18 · Current Pharmaceutical Design
The authors' central claim is that BPC-157's tissue protection routes through vascular recruitment — activating vessels to reach injury sites or open alternate circulation when the primary route is blocked.
- 2018Reviewmoderate
The International Society for the Study of Women's Sexual Health Process of Care for Management of Hypoactive Sexual Desire Disorder in Women
Clayton AH, Goldstein I, Kim NN, +14 · Mayo Clinic Proceedings
The ISSWSH consensus algorithm for HSDD diagnosis and treatment — biopsychosocial assessment first, modifiable-factor management second, then central-acting pharmacotherapy with menopausal-status-stratified selection — produced via modified Delphi across 17 international panelists.
- 2018Meta-analysismoderaten=1,879
Safety and efficacy of Cerebrolysin in early post-stroke recovery: a meta-analysis of nine randomized clinical trials
Bornstein NM, Guekht A, Vester J, +7 · Neurological Sciences
Bornstein 2018 is the manufacturer-aligned meta-analysis that pooled nine Cerebrolysin RCTs across 1,879 patients on the primary NIHSS analysis and reported superiority on NIHSS at day 30 — the positive synthesis the Cochrane review reads more skeptically.
- 2018Reviewmoderate
Regenerative and Protective Actions of the GHK-Cu Peptide in the Light of the New Gene Data
Pickart L, Margolina A · International Journal of Molecular Sciences
Gene-expression analysis suggests GHK regulates dozens of pathways involved in tissue remodeling — a breadth unusual for a tripeptide and the basis for the renewed scientific interest in copper-peptide therapeutics beyond cosmetics.
- 2017Mechanisticmoderate
Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis
Xiao B, Xu Z, Viennois E, +6 · Molecular Therapy
Hyaluronic-acid-functionalised polymeric nanoparticles delivered KPV to inflamed colonic tissue at a 12,000-fold lower effective concentration than the free tripeptide and accelerated mucosal healing in DSS colitis — proof-of-concept that the KPV translational problem may be delivery rather than activity.
- 2016Mechanisticmoderaten=30
Selank administration affects the expression of some genes involved in GABAergic neurotransmission
Volkova A, Shadrina M, Kolomin T, +4 · Frontiers in Pharmacology
Forty-five genes changed expression 1 hour after a single intranasal 300 µg/kg dose of Selank in rat frontal cortex, with strong positive correlation (r=0.86) to GABA's own effect pattern; by 3 hours, Selank uniquely drove a 128-fold increase in hypocretin (Hcrt) expression — a candidate explanation for why Selank does not produce the sedation that benzodiazepines do.
- 2016Opinionmoderate
Welcome to the ICD-10 code for sarcopenia
Anker SD, Morley JE, von Haehling S · Journal of Cachexia, Sarcopenia and Muscle
The October 2016 assignment of ICD-10-CM code M62.84 separated sarcopenia from cachexia, disuse atrophy, and inflammatory myopathy — the bureaucratic act that formalized sarcopenia as a discrete clinical entity rather than an aspect of frailty or aging in general.
- 2016Reviewmoderate
Definitions of Sexual Dysfunctions in Women and Men: A Consensus Statement From the Fourth International Consultation on Sexual Medicine 2015
McCabe MP, Sharlip ID, Atalla E, +6 · Journal of Sexual Medicine
The Fourth ICSM consensus reconciliation of DSM-5, ICD-10, and society-specific definitions for sexual dysfunctions — the framework reference for HSDD, FSIAD, female orgasmic disorder, and genito-pelvic pain/penetration disorder against which contemporary trials are designed and contemporary pharmacology is labeled.
- 2015Reviewmoderate
Historical review of thymosin α 1 in infectious diseases
Camerini R, Garaci E · Expert Opinion on Biological Therapy
Camerini and Garaci — the field's senior authors — survey three decades of thymosin α-1 clinical data: hepatitis B and C, sepsis, aspergillosis in bone-marrow transplant recipients, vaccine adjunction in immunosenescent populations. The synthesis that frames the molecule's mechanism (TLR-9 / TLR-2 antagonism, IDO induction in dendritic cells, T-cell maturation) and its place in modern infectious-disease management.
- 2014Reviewmoderate
The cardiovascular action of hexarelin
Mao Y, Tokudome T, Kishimoto I · Journal of Geriatric Cardiology
Synthesis of the hexarelin cardiac biology: acute LVEF improvement, ischemia-reperfusion protection in hypophysectomised rats, attenuation of cardiac fibrosis and LV hypertrophy, suppression of cardiomyocyte apoptosis — a body of work mechanistically anchored to CD36 binding that no other GHRP has accumulated.
- 2013Reviewmoderaten=925
Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans
Stier H, Vos E, Kenley D · Journal of Endocrinology and Metabolism
Integrated safety across six randomised, double-blind, placebo-controlled AOD-9604 trials (~925 subjects, doses to 54 mg oral, durations to 24 weeks): no IGF-1 elevation, no insulin resistance, no impaired glucose tolerance, no anti-AOD-9604 antibodies, and no serious adverse events attributed to study drug. The published file that compounding-pharmacy AOD-9604 marketing in 2026 most commonly cites.
- 2010Reviewmoderate
The melanocortin system in control of inflammation
Catania A, Lonati C, Sordi A, +3 · TheScientificWorldJournal
The Milan group's synthesis of two decades of melanocortin anti-inflammatory work — alpha-MSH and KPV across endotoxin shock, hepatic ischemia-reperfusion, brain inflammation, intestinal inflammation, and rheumatoid arthritis — with explicit attention to how the C-terminal tripeptide preserves activity while shedding the pigmentary signal that makes the parent hormone clinically unworkable for chronic anti-inflammatory use.
- 2010Mechanisticmoderate
The nootropic and analgesic effects of Semax given via different routes
Manchenko DM, Glazova NYu, Levitskaya NG, +3 · Neuroscience and Behavioral Physiology
The Manchenko / Glazova / Levitskaya route-dissociation paper: intraperitoneal Semax produces both nootropic and analgesic effects in white rats with different dose-response curves, while intranasal Semax produces a stronger nootropic effect than i.p. but no analgesic effect at all — the operational basis for Semax's clinical nasal-drop route convention.
- 2008Reviewmoderate
Investigation of the spectrum of physiological activities of the heptapeptide Semax, an ACTH(4-10) analogue
Levitskaya NG, Glazova NYu, Sebentsova EA, +5 · Neurochemical Journal
The Ashmarin / Moscow State University group's decade-on synthesis of the Semax research program — the thesis that the Pro-Gly-Pro stabilization separated melanocortin neurotropic activity from hormonal activity, enabling chronic dosing without engaging the systemic stress axis.
- 2008Reviewmoderate
α-Melanocyte-stimulating hormone and related tripeptides: biochemistry, antiinflammatory and protective effects in vitro and in vivo, and future perspectives for the treatment of immune-mediated inflammatory diseases
Brzoska T, Luger TA, Maaser C, +2 · Endocrine Reviews
The canonical Endocrine Reviews synthesis of alpha-MSH and its C-terminal tripeptide KPV across fever, dermatitis, vasculitis, arthritis, colitis, uveitis, and brain inflammation — the field's high-water-mark review of the pharmacophore-dissection argument for KPV as a non-pigmenting anti-inflammatory.
- 2004RCTmoderate
Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in healthy males and patients with mild-to-moderate erectile dysfunction
Diamond LE, Earle DC, Rosen RC, +2 · International Journal of Impotence Research
First-in-human safety and efficacy study of intranasal PT-141 in healthy men and men with erectile dysfunction — established the central-mechanism erectile response, dose-related flushing and nausea profile, and the pharmacokinetic floor on which Palatin's male-indication development program was built before it was abandoned for the eventual female HSDD approval.
- 2003Mechanisticmoderate
The optimizing action of the synthetic peptide Selank on a conditioned active avoidance reflex in rats
Kozlovskii II, Danchev ND · Neuroscience and Behavioral Physiology
Selank at 300 µg/kg significantly activated learning in rats with initially poor learning ability, with effects visible after the first dose on training day 1; in normal-learning rats the peak effect appeared on day 3 of repeated administration. The cognitive-optimization companion to the anxiolytic mechanism papers.
- 2003Cohortmoderaten=266
Peptides of pineal gland and thymus prolong human life
Khavinson VKh, Morozov VG · Neuroendocrinology Letters
Khavinson + Morozov's 266-elderly geroprotective dataset, published in English in Neuroendocrinology Letters one year after the original Russian-language Advances in Gerontology paper. The English version is the international-readership companion to the Russian primary publication.
- 2002Mechanisticmoderate
Effects of Selank on behavioral reactions and activities of plasma enkephalin-degrading enzymes in mice with different phenotypes of emotional and stress reactions
Sokolov OYu, Meshavkin VK, Kost NV, +1 · Bulletin of Experimental Biology and Medicine
The bridge between Kost 2001 in vitro mechanism and Zozulya 2008 clinical biomarker: in BALB/c mice (high anxiety phenotype), 100 µg/kg Selank produced an anxiolytic effect and prolonged plasma leu-enkephalin half-life; in C57BL/6 mice (low anxiety phenotype), it did neither. Strain-dependent responsivity consistent with an opioidergic mechanism.
- 2002Cohortmoderaten=266
Geroprotective effect of thymalin and epithalamin
Khavinson VKh, Morozov VG · Advances in Gerontology (Uspekhi Gerontologii)
266 elderly participants over 6–8 years on Khavinson's thymic and pineal peptide extracts — the longest-duration human geroprotective dataset published Russian-only, reporting a 2.0–4.1-fold mortality decrease against age-matched controls.
- 2001Mechanisticmoderate
Semax and Selank inhibit the enkephalin-degrading enzymes of human serum
Kost NV, Sokolov OYu, Gabaeva MV, +3 · Russian Journal of Bioorganic Chemistry
The foundational mechanism paper: Semax and Selank inhibit human serum enkephalin-degrading enzymes in vitro with IC50 values of 10 µM and 20 µM respectively — roughly three orders of magnitude more potent than the standard inhibitor puromycin (IC50 10 mM).
- 2000Mechanisticmoderate
The tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ stimulates matrix metalloproteinase-2 expression by fibroblast cultures
Siméon A, Emonard H, Hornebeck W, +1 · Life Sciences
GHK-Cu raised MMP-2 levels, MMP-2 mRNA, and TIMP-1/TIMP-2 secretion in fibroblast cultures — and the effect was driven by the copper ion rather than the bare tripeptide. The second-pillar mechanistic primary establishing GHK-Cu as a coordinated matrix-remodelling signal rather than a one-way collagen-deposition driver.
- 1998Mechanisticmoderate
α-Melanocyte-stimulating hormone inhibits the nuclear transcription factor NF-κB activation induced by various inflammatory agents
Manna SK, Aggarwal BB · Journal of Immunology
The foundational in-vitro demonstration that alpha-MSH and its C-terminal tripeptide KPV block NF-κB activation across diverse stimuli — TNF-α, IL-1, phorbol ester, hydrogen peroxide, LPS, ceramide, and okadaic acid — at low nanomolar concentrations, inhibiting IκBα degradation and blocking p65 nuclear translocation in human myeloid and lymphoid cell lines.
- 1997Cohortmoderaten=110
Effectiveness of Semax in the acute period of hemispheric ischemic stroke (a clinical and electrophysiological study)
Gusev EI, Skvortsova VI, Miasoedov NF, +3 · Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
The foundational Russian Semax stroke trial: 30 patients with acute hemispheric ischemic stroke received 12–18 mg/day intranasal Semax for 5–10 days added to combined intensive therapy and were compared to 80 conventionally treated controls — accelerated regression of motor and general cerebral deficits was the primary clinical finding, anchored by EEG mapping and somatosensory evoked potential correlates.
- 1996RCTmoderaten=36
Synthetic ACTH analogue Semax displays nootropic-like activity in humans
Kaplan AY, Kochetova AG, Nezavibatko VN, +2 · Neuroscience Research Communications
The first international report of Semax cognitive effects in humans, from the Ashmarin inventor group at Moscow State University — three sub-studies (operator performance, EEG during cognitive load, EEG under post-hyperventilation cerebral ischaemia) establishing a long-lasting (20-24 hr post single intranasal dose) cognitive signal at 0.25-1.0 mg.
- 1988Mechanisticmoderate
Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+
Maquart FX, Pickart L, Laurent M, +3 · FEBS Letters
The foundational mechanistic primary: GHK-Cu stimulated fibroblast collagen synthesis with peak activity at 10⁻⁹ M, independent of any change in cell number — and the GHK triplet sequence exists inside the alpha-2(I) collagen chain itself, suggesting GHK is liberated by wound-site proteases to drive in-situ repair.
- 1987RCTmoderaten=14
Effects of delta-sleep-inducing peptide on 24-hour sleep-wake behaviour in severe chronic insomnia
Schneider-Helmert D · European Neurology
Across 14 middle-aged chronic insomniacs given DSIP for seven consecutive nights under double-blind placebo control, night-sleep efficiency rose to control-population values and the effect persisted through the first placebo washout night — the cleanest single-investigator EEG-monitored evidence for DSIP in disturbed human sleep.
T3·Expert-primary work
Domain-expert primary sources outside the journal pipeline — lectures, podcasts, position papers.
4 sources
- 2026Reviewmoderate
Triple Hormone Receptor Agonism: The Role of Retatrutide in Addressing Cardiovascular-Kidney-Metabolic (CKM) Syndrome: A Comprehensive Review
Pillai AA, Godin SL, Frishman WH, +1 · Cardiology in Review
A cardiology-group synthesis of retatrutide's Phase 2 data: 12 mg weekly drives 24.2% body-weight reduction at 48 weeks with 63% achieving ≥20% loss, 2.02% HbA1c reduction with 27% reaching normoglycemia, and 82.4% relative reduction in hepatic fat — alongside an 8.79 mm Hg systolic-pressure drop and a chronotropic safety signal worth monitoring.
- 2026Meta-analysismoderaten=63,909
A systematic review and meta-analysis of the efficacy and safety of pharmacological treatments for obesity in adults: 2026 Update
Ciudin Mihai A, Baker JL, Belancic A, +3 · medRxiv (preprint)
A network meta-analysis pooling 66 RCTs and 63,909 patients across six obesity management medication classes finds tirzepatide and semaglutide as the only compounds exceeding 10% total body weight loss, with semaglutide reducing MACE and all-cause mortality, both incretins benefiting heart-failure outcomes and MASH remission, tirzepatide improving obstructive sleep apnoea, semaglutide improving knee osteoarthritis pain remission and liver fibrosis — and no OMM associated with increased serious adverse events.
- 2026Cohortmoderate
Semaglutide is associated with improved breast cancer survival, lower metastatic burden, and a dose-survival relationship uncoupled from weight-loss magnitude
Murugadoss K, Venkatakrishnan AJ, Soundararajan V · medRxiv (preprint)
In a federated EHR network of nearly 29 million patients with 1:1 propensity-matched pooled-comparator analyses, semaglutide-treated breast cancer patients had 54 deaths/2,433 (2.2%) versus 395 deaths/2,433 (16.2%) in metformin/SGLT2i/DPP4i comparators over 24 months (log-rank P<0.001); high-dose semaglutide (≥1.7 mg) had ~1.0% event rate vs ~4.5% in low-dose (0.25–1.0 mg, P=0.034), while weight-loss strata did not separate survival (P=0.22) — and any-metastasis incidence was 7.0% vs 15.0% (rate ratio 0.5, P<0.001).
- 2006Reviewmoderate
Delta sleep-inducing peptide (DSIP): a still unresolved riddle
Kovalzon VM, Strekalova TV · Journal of Neurochemistry
Russian sleep researchers Kovalzon and Strekalova argue that after three decades of work, the 'DSIP is a sleep factor' hypothesis remains weakly documented — no receptor identified, no gene confirmed, no consistent acute sleep-induction effect in standardised paradigms. The most rigorous published skepticism toward the foundational DSIP claim.