GLP-1 Tracker: Full Update Log

Full update log

• Aug 7, 2026Amycretin (Novo Nordisk) — 'zenagamtide (formerly amycretin)' in the papers' own words — had both halves of its Phase 2 type 2 diabetes dose-finding programme published in The Lancet on 30 July 2026, online ahead of print. Both ran under a single master protocol (NCT06542874) at 83 sites in 11 countries, 36 weeks each, in adults on metformin with or without an SGLT2 inhibitor. The once-daily oral trial (n=186; maintenance doses 6, 25, and 50 mg; DOI 10.1016/S0140-6736(26)01247-X) cut HbA1c by 0.9, 1.3, and 1.4 percentage points from a 7.9-8.1% baseline, all significant against placebo (treatment differences -0.5 to -1.09 pp); gastrointestinal adverse events hit 26%, 41%, and 47% of the three dose groups against 23% on placebo, with serious adverse events in 4% of zenagamtide participants, none on placebo, and no deaths. The once-weekly injectable trial (n=262; doses 0.4-40 mg; DOI 10.1016/S0140-6736(26)01248-1) — the one presented at ADA 2026 and already in the tracker — cut HbA1c by 0.9 points at the lowest dose to 1.7 at the highest (treatment differences -0.77 to -1.56 pp, significant across the dose range), with mostly mild-to-moderate GI adverse events, serious adverse events in 8% of participants across all groups including placebo, and no deaths. Neither abstract reports weight-loss figures — the up-to-14.6% number in the tracker comes from the ADA 2026 presentation, not these papers. The papers' background sections describe zenagamtide as a unimolecular agonist of GLP-1, amylin, and calcitonin receptors; the titles bill it as a GLP-1 and amylin receptor agonist.
• Aug 1, 2026Survodutide (Boehringer Ingelheim / Zealand Pharma) now shows SYNCHRONIZE-2 alongside the obesity trial that was already listed. SYNCHRONIZE-2 treated 752 people with type 2 diabetes and a BMI of 27 or above, at 133 sites in 19 countries, on weekly survodutide up-titrated to 3.6 mg or 6.0 mg against placebo for 76 weeks. Its two primary endpoints were the percentage change in body weight and the share of people losing 5% or more. The trial completed in December 2025. Eight months on, no efficacy results have been released; the only publication so far describes the baseline characteristics of the people enrolled (Wharton et al., Diabetes, Obesity and Metabolism, DOI 10.1111/dom.70263). It matters for anyone comparing these drugs, because weight loss is reliably smaller in people with type 2 diabetes than in people without it, and SYNCHRONIZE-1 — the trial behind survodutide's headline number here — excluded them. Survodutide's cardiovascular outcomes trial, SYNCHRONIZE-CVOT, completed in June 2026 and is also still unreported.
• Jul 23, 2026Retatrutide (Lilly) reported topline results from TRIUMPH-2 and TRIUMPH-3, taking it to five positive Phase 3 trials. TRIUMPH-2 (1,152 people with type 2 diabetes and obesity or overweight, 80 weeks) produced 20.8% weight loss at 12 mg against 4.0% on placebo, with HbA1c down 1.5 points from a baseline of 7.7%. TRIUMPH-3 (1,949 people with severe obesity and established cardiovascular disease, 80 weeks) produced 22.6% at 12 mg against 3.2%. Both figures are below the 28.3% of TRIUMPH-1, which is expected — diabetes and advanced cardiometabolic disease both blunt weight loss on these drugs — and the tracker's headline number stays at 28.3% because that is the obesity trial. The cardiovascular result needs care: TRIUMPH-3 was not powered to test heart outcomes and Lilly reports that events "occurred less frequently than anticipated" in both arms. Broad events ran 44 on retatrutide vs 52 on placebo (hazard ratio 0.82, CI 0.55-1.22); the narrower measure of cardiovascular death, heart attack and stroke ran 27 vs 23 (hazard ratio 1.12, CI 0.64-1.96). Neither is statistically meaningful, and the more favourable versions Lilly also published come from an analysis that was not pre-specified. Cardiovascular risk factors did improve clearly at the top dose: triglycerides -37.0%, non-HDL cholesterol -16.5%, systolic blood pressure -9.3 mmHg, hsCRP -51.2%. The nerve-sensation side effect seen in earlier trials appeared again but at lower rates (7.3% and 6.4% at 12 mg vs 12.5% in TRIUMPH-1), while discontinuation for side effects was highest in the sickest group at 13.5%. Finally, the expected FDA submission has moved: the tracker previously showed Q4 2026, and Lilly now says it will file in Q1 2027 while it completes the manufacturing data package. Neither trial is peer-reviewed yet.
• Jul 21, 2026Corrections pass, same day. An earlier update today claimed every percentage on this page matched its published paper rather than the sponsor's press release. That was not yet true, and the biggest offender was semaglutide: the 20.7% figure is Novo's trial-product estimand, while the published coprimary endpoint in Lancet Diabetes & Endocrinology is 18.7% against 3.9% on placebo. The card now leads with 18.7% and names both. Tirzepatide is 20.9%, the published SURMOUNT-1 number, not the 21% rounding. CagriSema's trial entries still carried the press figures of 22.7% and 15.7% after the headline had been corrected, so the card contradicted itself; both now read 20.4% and 13.7%. Two claims about semaglutide have been rewritten because they outran their evidence: the knee-osteoarthritis entry asserted the benefit 'exceeded what weight loss alone predicts', which the trial never tested or claimed, and the placebo group in that trial achieved about two thirds of the pain relief; and the bone entry cited a small trial at the 1.0 mg diabetes dose whose primary endpoint was negative, which is now stated plainly and downgraded from a harm to a signal. Retatrutide's knee-pain figure now shows the 40.3% placebo response alongside it. Tirzepatide's heart-failure symptom scores were wrong and are now the published 19.5 against 12.7. Self-pay pricing and Medicare coverage for semaglutide and tirzepatide were about a year out of date, and both omitted that the Medicare GLP-1 Bridge covers Wegovy and Zepbound, not only Foundayo. Stage labels have been split so a drug approved in China or filed in Korea no longer reads as though it were still in trials, and 'pre-Phase 3' no longer covers everything from a Phase 1 asset to one with Phase 3 already registered.
• Jul 21, 2026Full accuracy audit — every molecule re-checked against ClinicalTrials.gov, the published papers and company releases. Four were shown at the wrong stage and are corrected: amycretin, elecoglipron and berobenatide are in Phase 3 (berobenatide's VESPER-4 has been recruiting since Dec 2025), and MET-233i is in Phase 2. Semaglutide was badly out of date: the ceiling is now 20.7% on Wegovy HD 7.2 mg, and MASH and the oral 25 mg dose are approved, not investigational. Several headline percentages have been corrected to match the papers they cite rather than the press releases — MariTide is 12.3-16.2% not ~20%, CagriSema 20.4% not 22.7%, survodutide 13.0% not 16.6%. Every percentage on the page now carries the conditions behind it: trial length, population, estimand, and whether it is an absolute or placebo-adjusted change. They are not directly comparable and the page no longer implies they are.
• Jul 21, 2026Added BI 3034701 (Boehringer Ingelheim / Gubra), the first GLP-1/GIP/NPY2 triple agonist to reach Phase 2 — NCT07662122, 300 participants, started 30 Jun 2026, announced 16 Jul 2026, primary completion Aug 2027. Zero efficacy data is public: the Phase 1 (NCT06352437, 125 participants, completed Oct 2025) produced only a tolerability statement. Notable as the first multi-receptor obesity drug carrying NPY2, a pathway where every standalone attempt has failed on tolerability (BI 1820237 discontinued; Novo's PYY1875 dropped in Phase 2).
• Jul 13, 2026Added a real-world bone and falls signal for semaglutide and tirzepatide: Chen et al., Osteoporosis International (online 11 Jul 2026, DOI 10.1007/s00198-026-08134-y, PMID 42435064). Retrospective TriNetX cohort of adults 65 and older with type 2 diabetes plus overweight or obesity, matched 1:1 against DPP-4 inhibitors: one-year femoral fracture risk was lower with semaglutide (0.3% vs 0.5%, HR 0.49; n=27,896) and tirzepatide (0.2% vs 0.4%, HR 0.45; n=12,808); falls were lower too (HR about 0.66 for both); the fracture benefit was larger at BMI 30 and above. Filed as a signal rather than an established benefit — this is observational, and the comparator is a DPP-4 inhibitor, not placebo. It sits alongside the existing bone-density and lean-mass harm findings: the fracture picture is genuinely mixed, not a reversal. Separately, the ACHIEVE-2 result (orforglipron vs dapagliflozin) that PubMed indexed on 11 Jul 2026 is the same Lancet paper already listed here (online-first 8 Jun 2026, PMID 42259339), now carrying its final indexing date — no new data.
• Jul 8, 2026Added HRS-7535 / KAI-7535 (Kailera/Hengrui oral small-molecule GLP-1 agonist) after the 7 Jul 2026 topline. This is a different drug from the injectable dual agonist ribupatide (KAI-9531/HRS9531) already listed here. China Phase 3 HARBOR-1 (obesity): -10.9% at 44 weeks and -11.1% at 50 weeks at 180 mg (efficacy estimand) vs -2.5% on placebo, but heavy GI side effects (vomiting up to 68.6%, nausea about 70%). OUTSTAND-2 (type 2 diabetes): HbA1c down 1.50 to 1.68% vs 1.28% for dapagliflozin. A global Phase 2 in the US and Australia, using gentler titration, reads out in 2027. Listed at phase 3 on the strength of the China-only Phase 3 — the same convention used for efpeglenatide and ribupatide. Source: Kailera press release.
• Jul 4, 2026Survodutide SYNCHRONIZE-1 citation and body-composition update. The obesity trial is now published in NEJM (7 Jun 2026, DOI 10.1056/NEJMoa2600751, PMID 42253238), so the trial and efficacy sources moved from the Boehringer press release to the paper itself. Added the ADA 2026 MRI body-composition substudy (lean mass 10.8% or less of tissue change, visceral fat -34%, liver fat -63%, 61% reaching liver-fat normalization) with an important caveat: those are MRI measurements, not DEXA, so they are not evidence of a unique muscle-sparing edge over drugs measured by DEXA — semaglutide looks similar by MRI. Compare the retatrutide muscle-sparing overclaim.
• Jun 11, 2026Added enicepatide (Roche/Carmot CT-388, now with INN; RO7795068) as a new molecule from the ADA 2026 wrap: Phase 2 CT388-103 22.5% placebo-adjusted at 48 wks (efficacy estimand; 18.3% treatment-regimen), 5.9% AE discontinuation; two Phase 3 obesity trials recruiting since Mar 2026 (NCT07351045/58). Petrelintide entry cross-referenced to the new name; combo Phase 2 NCT07589686 starts mid-2026.
• Jun 10, 2026Journal citations upgraded: ACHIEVE-2 moved from press-release reporting to the published paper (Lancet, 8 Jun 2026, DOI 10.1016/S0140-6736(26)00800-7), and the ACHIEVE-3 source was upgraded from an Eli Lilly press release to the Lancet DOI (10.1016/S0140-6736(26)00202-3, published Mar 2026). Both are now cited on the orforglipron card. REIMAGINE 1-3, ACHIEVE-5 (JAMA) and TRANSCEND-T2D-1 already carried journal DOIs.
• Jun 9, 2026ADA 2026 follow-ups: (1) Retatrutide TRIUMPH-4 upgraded from topline reporting to the full ADA 2026 data — weight -28.7% (12 mg) and -26.4% (9 mg) vs -2.1% on placebo at 68 weeks, WOMAC knee pain -74 to -76% vs -40% on placebo, 12-14% pain-free vs 4.2%; source switched to medical.lilly.com. (2) Orforglipron ATTAIN-1 and ATTAIN-2 menopause post-hoc added (perimenopausal -14.4% / -30.4 lb, postmenopausal -14.1%, premenopausal -12.8%; more than 1,500 women; presented 7 Jun). (3) A class-level cancer signal added to semaglutide's beyond-weight-loss effects: GLP-1 receptor agonist users had 41% lower incidence of obesity-associated cancers (HR 0.59, Annals of Oncology 2026, PMID 42252247; observational). (4) Heart-failure trials added: semaglutide STEP-HFpEF (NEJM 2023) and tirzepatide SUMMIT (NEJM 2025).
• Jun 8, 2026CagriSema REIMAGINE 1-3 peer-reviewed (7 Jun 2026): REIMAGINE 1 and 2 in Lancet Diabetes & Endocrinology, REIMAGINE 3 in The Lancet. All three are now cited to the published papers with DOIs. REIMAGINE 2 confirmed superiority to semaglutide 2.4 mg in type 2 diabetes (HbA1c -1.91% vs -1.76%, weight -14.2% vs -10.2%, 43% lost 15% or more).
• Jun 7, 2026Retatrutide TRIUMPH-1 full obesity data presented at ADA 2026 (n=2,339, 80 wks): -28.3% weight at 12 mg (-25.9% at 9 mg, -19.0% at 4 mg), 65.3% reached BMI <30. Secondary endpoints at 12 mg: knee-osteoarthritis pain -73.1%, obstructive sleep apnea events -60.6%, triglycerides -41%, systolic BP -12.3 mmHg. Tolerability cost: 11.3% discontinued at 12 mg for adverse events vs 4.9% placebo.
• Jun 7, 2026Retatrutide heart-rhythm early signal logged (one to watch, not a verdict): in TRANSCEND-T2D-1 (n=403 treated) 7 patients had arrhythmias and 3 had major cardiovascular events vs 0 on placebo, with pulse up ~1 bpm. Because the glucagon arm can raise heart rate, it is the receptor to monitor, but trial investigators (Bajaj, Drucker, Seeley) call the case counts too small to draw conclusions; the dedicated cardiovascular-outcomes trial reads out ~2029.
• Jun 7, 2026JAMA published two phase 3 incretin trials together: mazdutide GLORY-2 (9 mg, n=461 Chinese adults with obesity, -16.65% mean weight at 60 weeks, 42% lost 20% or more) and orforglipron ACHIEVE-5 (n=546, added on to insulin glargine, HbA1c down as much as 1.88% at 40 weeks), with a joint editorial (Gadde and Heymsfield). GLORY-2 added with its trial and paper citations; ACHIEVE-5 moved from topline reporting to the published paper. Numbers reconciled to the published JAMA figures (earlier 20.1% / 2.1% press estimands replaced).
• Jun 7, 2026ADA 2026 day 3: mazdutide DREAMS-3 added (beat semaglutide head-to-head in Chinese T2D + obesity); elecoglipron (AstraZeneca/Eccogene oral GLP-1, AZD5004) added as a new pipeline molecule heading to Phase 3.
• Jun 6, 2026Retatrutide TRANSCEND-T2D-1 published in The Lancet. Early type 2 diabetes monotherapy: HbA1c down 1.94% and weight down 15.3% at 12 mg; dysesthesia milder in T2D (2-4%).
• Jun 6, 2026ADA 2026 readouts added: orforglipron ACHIEVE-2/4/5, CagriSema REIMAGINE 1-3, zenagamtide (amycretin) phase 2, survodutide SYNCHRONIZE-1, berobenatide (Pfizer) VESPER-1/2/3.
• Jun 6, 2026Retatrutide dysesthesia and UTI safety signal logged (up to ~21% dysesthesia at 12 mg in the TRIUMPH-4 obesity trial). Berobenatide promoted to phase 2 with Pfizer's once-monthly strategy.
• Aug 4, 2026Pfizer discontinued two clinical-stage obesity programmes: MET-224o, the oral ultra-long-acting GLP-1 acquired with Metsera, and PF-07976016, a Phase 2 GIPR antagonist dropped after Phase 2a data on a liraglutide background. Pfizer says it still wants to target the GIP receptor. Its only remaining oral GLP-1 is PF-08642534 (YP05002, licensed from YaoPharma), added here as a watch. The two Metsera assets tracked below, berobenatide and MET-233i, are unaffected.
• Aug 16, 2026The MHRA authorised orforglipron (Foundayo) on 10 August 2026, making the UK the first country in Europe to approve a GLP-1 tablet for weight management and type 2 diabetes. The weight-management indication mirrors the US: BMI 30+, or 27-30 with at least one weight-related comorbidity, alongside diet and activity; the UK label also covers glycaemic control in insufficiently controlled type 2 diabetes — an indication orforglipron does not yet hold in the US. Dosing starts at 0.8 mg once daily and escalates through 2.5, 5.5, 9, and 14.5 to 17.2 mg, with at least a month at each level, taken any time of day with no food or water restrictions. It is not available on the NHS; that decision follows a NICE evaluation. Primary source: gov.uk press release, 10 Aug 2026.
• Aug 16, 2026Some coverage of Zealand Pharma's H1 2026 report (13 Aug 2026) read as if petrelintide had advanced into Phase 3. The report's own wording is forward-looking: Zealand 'announced [the] decision to advance petrelintide into Phase 3 trials in H2 2026' and, with Roche, 'expect[s] to initiate registrational Phase 3 trials with petrelintide monotherapy' in H2 2026. ClinicalTrials.gov listed six petrelintide studies as of 16 Aug 2026 — Phases 1 and 2 only, no Phase 3 registration. The nearest registered new step is ZYNERGY (NCT07589686), the Phase 2 petrelintide + enicepatide combination, estimated to start 30 Sep 2026.