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
- Peptides covered
- 44
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- 100%
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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.
77 sources
- 2026Mechanisticstrong
Cav3.1 is a neuronal leucine sensor that mediates satiety and weight loss in response to dietary protein
Tsang AH, Heeley N, Alcaino C, +3 · Cell Metabolism
Cambridge Institute of Metabolic Science group identifies Cav3.1 — a T-type voltage-gated calcium channel — as the hypothalamic POMC-neuron leucine sensor that mediates protein-induced satiety, and shows pharmacological Cav3.1 activation in the mediobasal hypothalamus drives weight loss in obese mice and potentiates liraglutide's anorectic response.
- 2026RCTstrongn=2,538
Shifts in waist-to-height ratio categories within tirzepatide groups: a post-hoc analysis of SURMOUNT-1
Sattar N, Tchang BG, Vincent RP, +3 · Journal of Endocrinological Investigation
Across 2,538 SURMOUNT-1 participants, 72 weeks of tirzepatide 10/15 mg moved 54.7% into a better waist-to-height-ratio category versus 9.6% with placebo, and 16.7% reached WHtR ≤0.49 — a non-obese-by-NICE-definition threshold — sustained to 176 weeks in the prediabetes subset.
- 2025RCTstrongn=610
Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight
Ji L, Jiang H, Bi Y, +7 · New England Journal of Medicine
GLORY-1 reported mean body-weight reductions of -12.55% on mazdutide 6 mg versus +0.45% on placebo at 32 weeks in Chinese adults with obesity — the first Phase 3 readout for a Chinese-developed incretin in a population the global obesity trials have under-recruited.
- 2025Reviewstrong
Retraction notice: 'The Procognitive and Synaptogenic Effects of Angiotensin IV-Derived Peptides Are Dependent on Activation of the Hepatocyte Growth Factor/c-Met System' and related Wright/Harding lab Dihexa publications
Journal of Pharmacology and Experimental Therapeutics (editorial) · Journal of Pharmacology and Experimental Therapeutics
April 2025 retraction notices removed two of the key Wright/Harding lab mechanism papers for Dihexa — Benoist 2014 on HGF/c-Met dependence and Kawas 2012 on AngIV analog development — following research-integrity investigations. The McCoy 2013 foundational paper has been under an expression of concern since 2021. The mechanism case for Dihexa is now substantially weaker than the public peptide-vendor literature acknowledges.
- 2025RCTstrongn=13,165
Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes
Nicholls SJ, Bhatt DL, Buse JB, +9 · New England Journal of Medicine
SURPASS-CVOT randomized 13,299 T2D patients with established atherosclerotic cardiovascular disease to tirzepatide versus dulaglutide; the MACE composite occurred in 12.2% on tirzepatide versus 13.1% on dulaglutide (HR 0.92, 95.3% CI 0.83–1.01), meeting non-inferiority but not demonstrating superiority.
- 2025RCTstrongn=3,417
Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity
Garvey WT, Blüher M, Osorto Contreras CK, +9 · New England Journal of Medicine
In the pivotal Phase 3 obesity trial (n=3,417, 68 weeks), CagriSema produced 20.4% mean weight loss under the treatment-policy estimand versus 3.0% on placebo — a strong absolute result that nevertheless landed below Novo Nordisk's publicly stated 25% target and triggered a roughly 20–26% stock decline when the topline read out in December 2024.
- 2025RCTstrongn=1,206
Cagrilintide–Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes
Davies MJ, Bajaj HS, Broholm C, +8 · New England Journal of Medicine
The Phase 3 type 2 diabetes pivotal trial for CagriSema — 13.7% mean weight loss and 73.5% reaching HbA1c ≤6.5% on CagriSema at 68 weeks, versus 3.4% / 15.9% on placebo — the diabetic-cohort counterpart to REDEFINE-1, with the same magnitude-blunting pattern across the incretin class repeated here.
- 2025RCTstrongn=95
Kisspeptin Administration Stimulates Reproductive Hormones but Does Not Affect Anxiety in Humans
Mills EG, Comninos AN, Dhillo WS · Journal of Clinical Endocrinology & Metabolism
A biologically active dose of kisspeptin-54 to 95 men and women produced no measurable effect on behavioral, biochemical, or physiological anxiety measures — a primary-negative result that disambiguates the limbic-circuit mood findings from a generalized anxiolytic claim.
- 2024RCTstrongn=386
Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial
Le Roux CW, Steen O, Lucas KJ, +3 · Lancet Diabetes Endocrinol
Survodutide 4.8 mg produced 14.9% mean body-weight reduction at 46 weeks versus 2.8% on placebo — the first Phase 2 obesity readout for a glucagon / GLP-1 dual agonist competitive with tirzepatide-class magnitudes.
- 2024RCTstrongn=293
A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis
Sanyal AJ, Bedossa P, Fraessdorf M, +7 · New England Journal of Medicine
MASH resolution without worsening of fibrosis was achieved by 47–62% of survodutide-treated patients versus 14% on placebo at 48 weeks — among the strongest histologic readouts in a non-cirrhotic MASH Phase 2 to date.
- 2024RCTstrongn=670
Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial
Aronne LJ, Sattar N, Horn DB, +3 · JAMA
Stopping tirzepatide after 36 weeks of successful weight loss produced 14.0% weight regain over the next year versus continued loss of 5.5% on the active drug — the discontinuation curve that frames every clinical conversation about GLP-1 cessation.
- 2024RCTstrongn=98
Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial
Sanyal AJ, Kaplan LM, Frias JP, +9 · Nature Medicine
At 24 weeks, retatrutide reduced liver fat by 82.4% at the 12-mg dose versus +0.3% on placebo, with 86% of high-dose recipients reaching normal liver fat (<5%) — the largest liver-fat reduction of any pharmacotherapy ever published in MASLD.
- 2024RCTstrongn=469
Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity
Malhotra A, Grunstein RR, Fietze I, +10 · New England Journal of Medicine
AHI fell by roughly 20 events per hour more on tirzepatide than placebo across both arms — the data that turned Zepbound into the first pharmacologic approval for moderate-to-severe obstructive sleep apnea in adults with obesity.
- 2024RCTstrongn=3,533
Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes
Perkovic V, Tuttle KR, Rossing P, +8 · New England Journal of Medicine
Once-weekly semaglutide 1 mg reduced major kidney disease events by 24% and all-cause mortality by 20% across 3,533 patients with T2D and CKD on contemporary background therapy — the most clinically rigorous positive peptide-class kidney trial ever conducted.
- 2024RCTstrongn=255
Safety, tolerability, and efficacy of NLY01 in early untreated Parkinson's disease: a randomised, double-blind, placebo-controlled trial
McGarry A, Rosanbalm S, Leinonen M, +7 · Lancet Neurology
A 36-week Phase 2 trial of NLY01 — a pegylated exenatide variant engineered for CNS exposure — found no difference from placebo on MDS-UPDRS-II+III in 255 early untreated Parkinson's patients, the largest negative GLP-1 readout in the disease to date.
- 2023RCTstrongn=281
Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA
Rosenstock J, Frias J, Jastreboff AM, +8 · Lancet
In type 2 diabetes, retatrutide 12 mg drove a 2.02% absolute HbA1c reduction at 24 weeks and 16.94% body-weight reduction at 36 weeks — both the largest published Phase 2 effects of any incretin-class molecule in the diabetic cohort, and meaningfully above the dulaglutide active comparator on both endpoints.
- 2023RCTstrongn=5,246
Cardiovascular Safety of Testosterone-Replacement Therapy
Lincoff AM, Bhasin S, Flevaris P, +8 · New England Journal of Medicine
Testosterone replacement was non-inferior to placebo on the primary composite cardiovascular endpoint (7.0% vs 7.3%, hazard ratio 0.96) in 5,246 hypogonadal men with prevalent or high cardiovascular risk over a mean 33-month follow-up — alongside elevated rates of atrial fibrillation, acute kidney injury, and pulmonary embolism that the primary endpoint did not capture.
- 2023RCTstrongn=529
Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity
Kosiborod MN, Abildstrøm SZ, Borlaug BA, +12 · New England Journal of Medicine
KCCQ-CSS improved 16.6 points on semaglutide versus 8.7 on placebo — among the largest patient-reported-outcome gains ever recorded in an HFpEF trial, in a phenotype long resistant to pharmacological intervention.
- 2023RCTstrongn=17,604
Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes
Lincoff AM, Brown-Frandsen K, Colhoun HM, +6 · New England Journal of Medicine
In 17,604 patients with established cardiovascular disease and overweight/obesity but no diabetes, weekly semaglutide 2.4 mg reduced the composite primary cardiovascular endpoint by 20% over a mean 40-month follow-up — the trial that took semaglutide from a metabolic drug to a cardiovascular intervention.
- 2023RCTstrong
Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial
Karaa A, Bertini E, Carelli V, +3 · Neurology
MMPOWER-3 provides Class I evidence that elamipretide does not improve the six-minute walk test or fatigue at 24 weeks compared with placebo in primary mitochondrial myopathy — the failed pivotal trial that ended SS-31's lead indication and reframed the molecule's clinical story.
- 2023RCTstrongn=938
Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial
Garvey WT, Frias JP, Jastreboff AM, +3 · Lancet
Tirzepatide produced 12.8% and 14.7% mean weight loss at 10 mg and 15 mg over 72 weeks in adults with both obesity and type 2 diabetes — roughly two-thirds the magnitude of SURMOUNT-1's non-diabetic cohort, but with HbA1c reduction from 8.0% to 5.9% at the higher dose.
- 2023RCTstrongn=338
Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial
Jastreboff AM, Kaplan LM, Frías JP, +8 · New England Journal of Medicine
At the 12-mg dose, mean body-weight reduction reached 24.2% at 48 weeks, with every treated participant achieving at least 5% weight loss and 83% reaching at least 15% — the largest published pharmacotherapy result to date.
- 2023RCTstrongn=579
Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial
Wadden TA, Chao AM, Machineni S, +3 · Nature Medicine
After a 12-week intensive lifestyle lead-in produced ≥5% weight loss, tirzepatide produced an additional 18.4% weight reduction over 72 weeks versus 2.5% on placebo — a total program effect of 24.3% from study start, the largest published response to a lifestyle-plus-pharmacotherapy obesity protocol.
- 2022RCTstrongn=327
Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension
Wilding JPH, Batterham RL, Davies M, +11 · Diabetes, Obesity and Metabolism
One year after stopping semaglutide, participants regained two-thirds of their lost weight (11.6 percentage points) — and cardiometabolic improvements reverted in parallel. The single most important paper for the discontinuation-rebound conversation.
- 2022RCTstrongn=2,539
Tirzepatide Once Weekly for the Treatment of Obesity
Jastreboff AM, Aronne LJ, Ahmad NN, +9 · New England Journal of Medicine
Mean weight loss at 72 weeks was 16.0%, 21.4%, and 22.5% on tirzepatide 5/10/15 mg versus 3.1% on placebo — the first non-surgical intervention to put more than half of treated patients past 20% weight loss in a Phase III trial.
- 2021RCTstrongn=1,961
Once-Weekly Semaglutide in Adults with Overweight or Obesity
Wilding JPH, Batterham RL, Calanna S, +11 · New England Journal of Medicine
Mean body-weight change at week 68 was -14.9% on semaglutide versus -2.4% on placebo, with 86.4% of treated participants achieving at least 5% weight loss — the trial that anchored the cultural moment around GLP-1 agonists for obesity.
- 2021RCTstrongn=831
Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer
Sartor O, de Bono J, Chi KN, +18 · New England Journal of Medicine
Median overall survival of 15.3 versus 11.3 months on 177Lu-PSMA-617 plus protocol-permitted standard of care versus standard of care alone (HR 0.62) — the registration result that extended the somatostatin-receptor theranostic framework of NETTER-1 onto a second receptor target and licensed peptide-radionuclide therapy in PSMA-positive metastatic castration-resistant prostate cancer.
- 2021RCTstrongn=803
Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial
Rubino D, Abrahamsson N, Davies M, +12 · JAMA
After a 20-week run-in producing 10.6% weight loss, participants who continued semaglutide lost an additional 7.9% over 48 weeks while those switched to placebo regained 6.9% — a 14.8-percentage-point divergence that defines the maintenance question for the entire GLP-1 class.
- 2021RCTstrongn=1,879
Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes
Frías JP, Davies MJ, Rosenstock J, +7 · New England Journal of Medicine
In the only major head-to-head trial of the modern GLP-1 class, tirzepatide at all three doses produced superior glycemic control to semaglutide 1 mg, with the 15-mg dose producing nearly twice the weight loss — the trial that established the dual-incretin advantage as more than a marginal difference.
- 2021Mechanisticstrong
Molecular Engineering of Insulin Icodec, the First Acylated Insulin Analog for Once-Weekly Administration in Humans
Kjeldsen TB, Hubálek F, Hjørringgaard CU, +15 · Journal of Medicinal Chemistry
Three insulin substitutions (A14E, B16H, B25H) plus a C20 fatty-diacid acylation at LysB29 — the molecular-engineering combination that produced a ~196-hour terminal half-life and made once-weekly basal insulin a clinical reality.
- 2021Mechanisticstrong
Development of Cagrilintide, a Long-Acting Amylin Analogue
Kruse T, Hansen JL, Dahl K, +12 · Journal of Medicinal Chemistry
The molecular design paper for cagrilintide — a stabilised, lipidated long-acting analogue of pramlintide engineered around the same C20-fatty-diacid + albumin-binding architecture that produced once-weekly semaglutide, here transplanted onto an amylin backbone.
- 2021Mechanisticstrong
MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis
Reynolds JC, Lai RW, Woodhead JST, +9 · Nature Communications
Acute exercise raised skeletal-muscle MOTS-c expression nearly 12-fold and circulating MOTS-c by approximately 50% in human volunteers; exogenous MOTS-c administered to mice approximately doubled treadmill running capacity at young, middle-aged, and old time points — the strongest single-paper integration of MOTS-c human physiology and mouse pharmacology to date.
- 2021RCTstrongn=706
Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial
Lau DCW, Erichsen L, Francisco AM, +7 · Lancet
The Phase 2 dose-finding monotherapy trial that established cagrilintide-alone performance — 10.8% weight loss at 26 weeks on cagrilintide 4.5 mg versus 9.0% on liraglutide 3.0 mg and 3.0% on placebo, a result consistent with an amylin agonist that operates through partially overlapping but mechanistically distinct satiety pathways from the GLP-1 class.
- 2020RCTstrongn=934
Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer
Shore ND, Saad F, Cookson MS, +12 · New England Journal of Medicine
Sustained castration through 48 weeks reached 96.7% on oral relugolix versus 88.8% on injectable leuprolide — the first head-to-head Phase III to put an oral GnRH antagonist directly against the depot-agonist standard of care in advanced prostate cancer.
- 2020Mechanisticstrong
Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist
Willard FS, Douros JD, Gabe MBN, +15 · JCI Insight
Tirzepatide is not a balanced dual GIP / GLP-1 agonist — it engages the GIP receptor with native-ligand potency and the GLP-1 receptor with approximately 5-fold weaker affinity, and at the GLP-1 receptor it is biased toward cAMP signaling over β-arrestin recruitment.
- 2020RCTstrongn=4,304
Dapagliflozin in Patients with Chronic Kidney Disease
Heerspink HJL, Stefánsson BV, Correa-Rotter R, +11 · New England Journal of Medicine
Dapagliflozin reduced the primary kidney composite by 39% across 4,304 CKD patients (with and without diabetes) — the landmark SGLT2-inhibitor trial that established the second pillar of contemporary CKD pharmacology onto which the GLP-1 class now stacks.
- 2019RCTstrongn=168
Six-Month Randomized, Multicenter Trial of Closed-Loop Control in Type 1 Diabetes
Brown SA, Kovatchev BP, Raghinaru D, +18 · New England Journal of Medicine
Hybrid closed-loop insulin delivery (Tandem Control-IQ) improved time-in-range from 61% to 71% at six months versus unchanged 59% on sensor-augmented pump therapy — the regulatory-grade evidence that anchored the modern hybrid closed-loop ecosystem.
- 2019RCTstrongn=737
Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma
Facon T, Kumar S, Plesner T, +27 · New England Journal of Medicine
MAIA established daratumumab-anchored D-Rd as the transplant-ineligible frontline standard, displacing bortezomib-VMP for the median-age-73 newly-diagnosed multiple myeloma population and shifting the practical baseline against which subsequent proteasome-inhibitor regimens are now measured.
- 2019RCTstrongn=61
Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial
Stanley TL, Fourman LT, Feldpausch MN, +16 · Lancet HIV
12-month randomized trial in HIV-associated NAFLD — tesamorelin reduced liver fat 37% on average, drove a third of treated participants below the 5% steatosis threshold, and prevented fibrosis progression on biopsy.
- 2019RCTstrongn=1,267
Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials
Kingsberg SA, Clayton AH, Portman D, +5 · Obstetrics and Gynecology
Both RECONNECT trials met their primary endpoints — bremelanotide produced statistically significant increases in sexual desire and reductions in associated distress in premenopausal women with HSDD — and form the basis for the FDA approval of Vyleesi in June 2019.
- 2018RCTstrongn=282
Clomiphene citrate and human chorionic gonadotropin are both effective in restoring testosterone in hypogonadism: a short-course randomized study
Habous M, Giona S, Tealab A, +8 · BJU International
In 282 fertility-preserving hypogonadal men randomized to clomiphene 50 mg daily, hCG 5,000 IU twice weekly, or both, all three arms produced equivalent testosterone restoration — and single-agent clomiphene was the simplest and cheapest of the three.
- 2018Mechanisticstrong
LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept
Coskun T, Sloop KW, Loghin C, +13 · Molecular Metabolism
The discovery paper for LY3298176 — later named tirzepatide — established the molecule as a single 39-residue, fatty-acid-conjugated peptide engineered to engage both the GIP and GLP-1 receptors with once-weekly pharmacokinetics, framing it explicitly as a unimolecular dual agonist rather than a co-administered combination.
- 2017RCTstrongn=62
A second dose of kisspeptin-54 improves oocyte maturation in women at high risk of ovarian hyperstimulation syndrome: a Phase 2 randomized controlled trial
Abbara A, Jayasena CN, Christopoulos G, +15 · Human Reproduction
A second dose of kisspeptin-54 ten hours after the first lifted the proportion of women achieving ≥60% mature-oocyte yield from 45% to 71% — without an increase in OHSS rates in a high-risk population.
- 2017RCTstrongn=1,689
Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist
Taylor HS, Giudice LC, Lessey BA, +19 · New England Journal of Medicine
Two replicate phase 3 trials established the first orally bioavailable GnRH antagonist for endometriosis pain — and the dose-proportional bone mineral density loss that the label-mandated duration ceilings have to manage.
- 2017RCTstrongn=229
Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors
Strosberg J, El-Haddad G, Wolin E, +33 · New England Journal of Medicine
Progression-free survival at 20 months was 65.2% on 177Lu-DOTATATE versus 10.8% on high-dose octreotide LAR — the result that opened peptide-receptor radionuclide therapy as an approved modality and licensed the somatostatin-receptor theranostic framework that now extends through PSMA-617 and beyond.
- 2016RCTstrongn=3,297
Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes
Marso SP, Bain SC, Consoli A, +13 · New England Journal of Medicine
In 3,297 high-cardiovascular-risk type 2 diabetes patients, weekly semaglutide reduced the composite primary cardiovascular endpoint by 26% over a median 2.1 years — the trial that established cardiovascular benefit for the GLP-1 class and presaged the 2023 SELECT result in obesity.
- 2016RCTstrongn=9,340
Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes
Marso SP, Daniels GH, Brown-Frandsen K, +14 · New England Journal of Medicine
Across 9,340 high-cardiovascular-risk type 2 diabetes patients followed a median of 3.8 years, daily liraglutide reduced the composite primary cardiovascular endpoint by 13% (HR 0.87, 95% CI 0.78–0.97; p=0.01 for superiority) and cardiovascular death by 22% — the first GLP-1 receptor agonist cardiovascular-outcomes trial to demonstrate superiority over placebo on the FDA's post-rosiglitazone safety pathway.
- 2016RCTstrongn=979
Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from two randomised, double-blind, phase 3 trials
Temel JS, Abernethy AP, Currow DC, +4 · Lancet Oncology
Lean body mass rose on anamorelin versus placebo in both trials (ROMANA 1: +0.99 vs −0.47 kg, p<0.0001; ROMANA 2: +0.65 vs −0.98 kg, p<0.0001) — but handgrip strength did not differentiate in either trial. The class-defining mass-without-strength result that shaped the regulatory split between Japan's approval and the EMA's rejection.
- 2015RCTstrongn=3,731
A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management
Pi-Sunyer X, Astrup A, Fujioka K, +9 · New England Journal of Medicine
In 3,731 non-diabetic adults with overweight or obesity, 56 weeks of daily liraglutide 3.0 mg produced a mean weight loss of -8.0% versus -2.6% on placebo — the pivotal trial that established once-daily GLP-1 receptor agonism as a chronic-weight-management therapy and underwrote Saxenda's 2014 FDA approval.
- 2015RCTstrongn=6,068
Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome
Pfeffer MA, Claggett B, Diaz R, +8 · New England Journal of Medicine
ELIXA established lixisenatide's cardiovascular safety in 6,068 post-ACS T2D patients with a primary MACE composite of 13.4% versus 13.2% on placebo (HR 1.02, 95% CI 0.89–1.17) — non-inferior but not superior.
- 2015Mechanisticstrong
The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance
Lee C, Zeng J, Drew BG, +8 · Cell Metabolism
MOTS-c — the first mitochondrial-encoded peptide characterized as a circulating signaling molecule — prevented age- and diet-induced insulin resistance in mice through skeletal-muscle AMPK activation.
- 2015Mechanisticstrong
Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide
Lau J, Bloch P, Schäffer L, +5 · Journal of Medicinal Chemistry
The molecular design paper for semaglutide — the C18 fatty diacid plus the Aib(8) substitution, paired together to produce week-long albumin binding and full DPP-4 resistance, were the design moves that opened once-weekly GLP-1 dosing as a clinical category.
- 2014Mechanisticstrong
Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity
Kraus D, Yang Q, Kong D, +16 · Nature
Antisense knockdown of nicotinamide N-methyltransferase in white adipose tissue and liver of diet-induced-obese mice protected against weight gain, improved insulin sensitivity, and elevated tissue SAM and NAD+ levels — without changes in food intake. The mechanistic anchor for every subsequent 5-Amino-1MQ paper.
- 2014RCTstrongn=204
Lanreotide in metastatic enteropancreatic neuroendocrine tumors
Caplin ME, Pavel M, Ćwikła JB, +13 · New England Journal of Medicine
Lanreotide Autogel 120 mg every 28 days cut the hazard of disease progression or death by 53% versus placebo in 204 patients with metastatic grade 1 or 2 enteropancreatic neuroendocrine tumors — the trial that extended the somatostatin-analog antiproliferative framework beyond the midgut sites covered by PROMID.
- 2013Mechanisticstrong
The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin
Birk AV, Liu S, Soong Y, +6 · Journal of the American Society of Nephrology
Birk and Szeto demonstrated that SS-31 binds cardiolipin selectively on the inner mitochondrial membrane, inhibits cytochrome c peroxidase activity, preserves cristae structure during ischemia, and accelerates ATP recovery after renal reperfusion — the foundational mechanism paper for every subsequent SS-31 indication.
- 2012RCTstrongn=86
Teduglutide reduces need for parenteral support among patients with short bowel syndrome with intestinal failure
Jeppesen PB, Pertkiewicz M, Messing B, +6 · Gastroenterology
63% of teduglutide-treated short-bowel-syndrome patients achieved 20–100% reduction in weekly parenteral-support volume versus 30% on placebo at 24 weeks — the pivotal Phase 3 result behind FDA approval and the closest precedent the GI-peptide field has for a peptide carrying a registration-quality program to a marketed indication.
- 2012RCTstrongn=1,070
Cerebrolysin in patients with acute ischemic stroke in Asia: results of a double-blind, placebo-controlled randomized trial
Heiss WD, Brainin M, Bornstein NM, +2 · Stroke
CASTA is the largest Cerebrolysin acute-stroke RCT ever conducted — 1,070 patients across Asia — and the primary endpoint was negative. The trial is the structural reason every honest reading of the Cerebrolysin literature has to address how to reconcile a large negative pivotal-scale trial with a positive manufacturer-aligned meta-analysis.
- 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%.
- 2010RCTstrongn=130
Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema
Cicardi M, Banerji A, Bracho F, +57 · New England Journal of Medicine
FAST-1 missed its primary endpoint at P=0.14 because the placebo arm recovered faster than expected; FAST-2 separated icatibant from oral tranexamic acid at 2.0 versus 12.0 hours, P<0.001 — the split that put icatibant on the path to regulatory approval once FAST-3 closed the placebo gap a year later.
- 2010Meta-analysisstrongn=806
Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data
Falutz J, Mamputu JC, Potvin D, +6 · Journal of Clinical Endocrinology & Metabolism
Pooled across two phase 3 trials in 806 ART-treated HIV patients with abdominal fat accumulation, tesamorelin reduced visceral adipose tissue and maintained the reduction for 52 weeks while preserving subcutaneous fat — the extended-evidence companion to the 2007 NEJM pivotal.
- 2009RCTstrongn=85
Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group
Rinke A, Müller H-H, Schade-Brittinger C, +11 · Journal of Clinical Oncology
Octreotide LAR 30 mg every 28 days extended median time to tumor progression from 6.0 to 14.3 months in patients with well-differentiated metastatic midgut neuroendocrine tumors — the first randomized controlled trial to establish a somatostatin analog as a tumor-control rather than purely symptom-control intervention.
- 2008Mechanisticstrong
Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin
Brines M, Patel NSA, Villa P, +13 · PNAS
An eleven-amino-acid peptide reproducing the aqueous face of helix B of human erythropoietin retains the tissue-protective activity of EPO across stroke, retinal, renal, and peripheral-nerve injury models while remaining inactive at the homodimeric EPO receptor — the foundational design paper for ARA-290 / cibinetide.
- 2008RCTstrongn=65
Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial
Nass R, Pezzoli SS, Oliveri MC, +7 · Annals of Internal Medicine
Daily oral MK-677 raised GH and IGF-1 to young-adult levels and added 1.1 kg of fat-free mass over a year — but the gain did not translate into measurable strength or functional improvement.
- 2008RCTstrongn=682
Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma
San Miguel JF, Schlag R, Khuageva NK, +18 · New England Journal of Medicine
VISTA established bortezomib-melphalan-prednisone as the frontline standard for transplant-ineligible multiple myeloma — time to progression 24.0 versus 16.6 months and a 31 percent reduction in mortality that persisted on 5-year follow-up — the trial that converted the proteasome-inhibitor class from a relapsed-disease therapy into first-line oncology and held that position for a decade.
- 2007RCTstrongn=412
Metabolic effects of a growth hormone-releasing factor in patients with HIV
Falutz J, Allas S, Blot K, +9 · New England Journal of Medicine
Visceral adipose tissue decreased by 15.2% on tesamorelin and rose 5.0% on placebo over 26 weeks (p<0.001) — the trial that earned tesamorelin its FDA indication and its credibility-flagship status on this site.
- 2006RCTstrong
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, +3 · Journal of Clinical Endocrinology & Metabolism
A single subcutaneous dose of CJC-1295 with DAC produced 2- to 10-fold GH elevations for six days and 1.5- to 3-fold IGF-1 elevations for nine to eleven days, with a plasma half-life of 5.8 to 8.1 days.
- 2005RCTstrongn=669
Bortezomib or high-dose dexamethasone for relapsed multiple myeloma
Richardson PG, Sonneveld P, Schuster MW, +18 · New England Journal of Medicine
Bortezomib improved time to progression to 6.22 months versus 3.49 months with high-dose dexamethasone in relapsed multiple myeloma — the pivotal trial that established the proteasome-inhibitor peptide-pharmacophore class as standard-of-care therapy and licensed full FDA approval of the first-in-class drug.
- 2005RCTstrongn=29
Low-Dose Human Chorionic Gonadotropin Maintains Intratesticular Testosterone in Normal Men with Testosterone-Induced Gonadotropin Suppression
Coviello AD, Matsumoto AM, Bremner WJ, +9 · Journal of Clinical Endocrinology and Metabolism
At 500 IU every other day, hCG maintained intratesticular testosterone 26% above baseline despite full pituitary suppression by exogenous testosterone — the foundational dose-response that anchors all subsequent hCG-during-TRT fertility-preservation protocols.
- 2002Mechanisticstrong
CD36 mediates the cardiovascular action of growth hormone-releasing peptides in the heart
Bodart V, Febbraio M, Demers A, +8 · Circulation Research
A radioactive photoactivatable hexarelin derivative cross-linked to an 84-kDa cardiac membrane protein identified by sequencing as CD36 — and the hexarelin coronary-perfusion-pressure effect was abolished in CD36-null mice and in CD36-deficient spontaneously hypertensive rats. The molecular identification of hexarelin's cardiac receptor.
- 1999Mechanisticstrongn=40
Pharmacokinetic-Pharmacodynamic Modeling of Ipamorelin, a Growth Hormone Releasing Peptide, in Human Volunteers
Gobburu JV, Agersø H, Jusko WJ, +1 · Pharmaceutical Research
Ipamorelin's terminal half-life is roughly two hours and clearance is 0.078 L/h/kg — short enough that the GH pulse it produces is over within six hours, the pharmacological signature behind its 'physiological pulse' reputation.
- 1998Mechanisticstrong
Ipamorelin, the first selective growth hormone secretagogue
Raun K, Hansen BS, Johansen NL, +4 · European Journal of Endocrinology
At doses more than 200-fold above the ED50 for GH release, Ipamorelin produced no significant elevation of ACTH, cortisol, prolactin, FSH, LH, or TSH — the selectivity that distinguished it from every prior GHRP.
- 1998RCTstrongn=3,867
Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)
UK Prospective Diabetes Study (UKPDS) Group · Lancet
Across 3,867 newly-diagnosed type 2 diabetes patients followed a median 10 years, intensive sulphonylurea-or-insulin therapy reduced microvascular endpoints by 25% — the landmark T2D companion to DCCT and the foundation of the contemporary HbA1c-target framework.
- 1994RCTstrongn=12
Growth hormone-releasing activity of hexarelin in humans. A dose-response study
Imbimbo BP, Mant T, Edwards M, +6 · European Journal of Clinical Pharmacology
Twelve adult male volunteers in a placebo-controlled rising-dose IV study; an ED50 of approximately 0.5 µg/kg, peak plasma GH at 30 minutes, return to baseline by 240 minutes — the foundational human pharmacokinetic and pharmacodynamic characterisation of hexarelin.
- 1993RCTstrongn=1,441
The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus
Diabetes Control and Complications Trial Research Group, Nathan DM, Genuth S, +6 · New England Journal of Medicine
Intensive insulin therapy reduced retinopathy development by 76% in primary prevention and slowed progression by 54% in secondary intervention across 1,441 type 1 diabetes patients followed a mean of 6.5 years — the landmark demonstration that microvascular complications track glycemic burden.
- 1992Mechanisticstrong
The cloning of a family of genes that encode the melanocortin receptors
Mountjoy KG, Robbins LS, Mortrud MT, +1 · Science
The original cloning paper for the melanocortin receptor family — identification of the murine and human MSH receptor and the human ACTH receptor as G-protein-coupled receptors, deposited in GenBank as X65633, X65634, and X65635. The molecular foundation of every melanocortin-targeted peptide on this site.
- 1979Mechanisticstrong
Expression in Escherichia coli of chemically synthesized genes for human insulin
Goeddel DV, Kleid DG, Bolivar F, +7 · Proceedings of the National Academy of Sciences of the United States of America
The paper that turned synthetic biology into pharmaceutical manufacturing — separate E. coli expression of the A and B chains as β-galactosidase fusions, chemical cleavage, in vitro chain reassembly, and a biologically active human insulin three years before Humulin reached the market.
- 1963Mechanisticstrong
Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide
Merrifield RB · Journal of the American Chemical Society
The 1963 JACS paper that introduced solid-phase peptide synthesis — anchoring the C-terminal amino acid to an insoluble polymer support and extending the chain through repeated coupling cycles. The methodology earned Merrifield the 1984 Nobel Prize in Chemistry and remains the workhorse of synthetic-peptide manufacturing six decades later.