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
- Peptides covered
- 44
- Tier 1 share
- 32%
- Matching filter
- 25
F·Filter
Reset allT1·Peer-primary literature
Randomized trials, peer-reviewed primary studies, and meta-analyses — the load-bearing layer of the corpus.
8 sources
- 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=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.
- 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.
- 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.
- 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.
- 2010Cohortstrongn=3,369
Identification of Late-Onset Hypogonadism in Middle-Aged and Elderly Men
Wu FC, Tajar A, Beynon JM, +18 · New England Journal of Medicine
Of nine candidate symptoms tested against the testosterone gradient, only three — poor morning erection, low libido, and erectile dysfunction — clustered syndromically with low testosterone, and the prevalence of symptom-and-biochemistry-confirmed late-onset hypogonadism in men aged 40–79 was approximately 2.1%.
- 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.
T2·Peer-secondary literature
Peer-reviewed reviews and cohort/observational work — context, not bedrock.
13 sources
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 2018Cohortsuggestiven=97
Circulating MOTS-c levels are decreased in obese male children and adolescents and associated with insulin resistance
Du C, Zhang C, Wu W, +7 · Pediatric Diabetes
Circulating MOTS-c was significantly lower in obese male Chinese children and adolescents than in normal-weight controls and correlated inversely with HOMA-IR — the first paediatric demonstration of the mitochondrial-derived-peptide-and-insulin-resistance association predicted by Lee 2015.
- 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.
- 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.
- 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.
- 1986Cohortsuggestiven=18
Efficacy of DSIP to normalize sleep in middle-aged and elderly chronic insomniacs
Schneider-Helmert D · European Neurology
18 chronic-insomnia patients across two age strata; middle-aged subjects (29–59) reached normal sleep values by end of one week of DSIP dosing, while elderly subjects (60–83) required the post-treatment follow-up week to achieve the same normalisation — an age-dependent response curve unique in the DSIP literature.
T3·Expert-primary work
Domain-expert primary sources outside the journal pipeline — lectures, podcasts, position papers.
4 sources
- 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).
- 2026Cohortsuggestiven=63,215
Legacy neuropsychiatric benefit after semaglutide is linked to maximum achieved dose and independent of the maximum weight lost
Murugadoss K, Venkatakrishnan A, Soundararajan V · medRxiv (preprint)
From 489,785 semaglutide-treated adults in a federated EHR network, 63,215 patients with baseline neuropsychiatric conditions showed broadly lower 2-year neuropsychiatric event risk versus propensity-matched metformin, SGLT2i and DPP-4i users; higher attained pre-landmark dose was independently associated with lower post-landmark incidence of substance-related, mood, anxiety, CNS-atrophy, neuromuscular, eating/sleep/behavioral and personality/impulse-control disorders — effects that were weight-loss-independent for most outcomes, with confirmed CNS GLP1R expression in hypothalamus, caudate, putamen, NAcc and cerebellum supporting a direct CNS engagement model.
- 2026Cohortsuggestiven=489,785
Semaglutide is associated with stiffness improvement and broad liver benefits with distinct dose- and weight-linked patterns
Soundararajan V, Venkatakrishnan AJ, Murugadoss K, +3 · medRxiv (preprint)
In a de-identified federated EHR network of 489,785 semaglutide-treated adults plus a paired elastography substudy of 326 patients, median liver stiffness fell from 4.85 to 3.9 kPa (−0.38 kPa, p<0.001); 40.8% achieved ≥20% reduction and 80% of those with cirrhosis-range baseline (≥12.5 kPa) hit that threshold — with stiffness improvement appearing in patients with no weight loss as often as in those with ≥10% weight loss, and hepatic GLP1R expression at only 0.0239% suggesting a largely non-direct mechanism.
- 2026Cohortsuggestiven=72
The Association Between Serum MOTS-c Levels and Myocardial Ischemia-Reperfusion Injury in Patients with Acute Myocardial Infarction: A Cross-Sectional Study
Peng L, Li Y, Duan X, +3 · Biomedicines
In 72 acute myocardial infarction patients undergoing PCI, postoperative peripheral serum MOTS-c levels were significantly lower in the 34 patients who developed myocardial ischemia-reperfusion injury versus the 38 who did not, with an adjusted odds ratio of 0.986 (95% CI 0.976-0.996) — the first human clinical-cohort biomarker data linking endogenous MOTS-c to acute cardiac injury.