Type-2 diabetes is the original GLP-1 indication and remains the largest payer-covered market for the class. Coverage on Peptide News Digest centers on Phase 3 readouts that move prescribing — SURPASS for tirzepatide, ACHIEVE for orforglipron, the SUSTAIN series for semaglutide — and on the cardiometabolic evidence that has expanded the indication framing.
A few threads beyond the core GLP-1s: Merck's enlicitide-decanoate (PCSK9) for related lipid management, and the Foundayo (orforglipron) launch as the first small-molecule oral GLP-1 to hit the T2D market. Real-world Truveta and IQVIA data continues to track how the trial signals translate to 12-month routine care.
Stories here cover Phase 3 readouts, head-to-head comparisons, and payer coverage decisions. See #diabetes for the broader category and #obesity for the weight-loss-specific thread.
Stanford University researchers presented retrospective cohort data at ENDO 2026 on June 13 from the Atropos Health Eos electronic health record dataset (~161 million patients seen in US community hospitals and academic medical centers, January 2016 to December 2023). Among adults with type 2 diabetes and no prior fractures or osteoporosis medication use, semaglutide was associated with a 15% lower fracture risk and greater weight loss versus other anti-obesity medications. Principal investigator Jairo Noreña framed the work as an early signal that semaglutide-driven weight loss may protect bone health in T2D, with prospective studies needed to confirm.
Lilly presented full Phase 3 data from the ACHIEVE program in type 2 diabetes at ADA 2026's Monday symposium. In the head-to-head ACHIEVE-3 trial, Foundayo (orforglipron) beat oral semaglutide across the primary and all key secondary endpoints, with 37.1% of patients on the highest Foundayo dose reaching HbA1c under 5.7% (normal range) versus 12.5% on the highest oral semaglutide dose tested. ACHIEVE-2 compared Foundayo to dapagliflozin; ACHIEVE-5 added it to insulin glargine. Lilly plans to submit Foundayo for FDA T2D approval by end of Q2 under the Commissioner's National Priority Voucher.
Novo Nordisk presented the full REIMAGINE 1/2/3 Phase 3 program in a Sunday symposium at ADA 2026, with simultaneous publication in The Lancet Diabetes & Endocrinology (REIMAGINE 1 and 2) and The Lancet (REIMAGINE 3). REIMAGINE 2 (n=2,713; 68 weeks) showed CagriSema 2.4/2.4 mg producing 14.2% weight loss and 1.91% HbA1c reduction versus 10.2% and 1.75% for semaglutide 2.4 mg alone. REIMAGINE 1 (n=189; 40 weeks) showed 13.8% weight loss and 1.8% HbA1c drop vs placebo. REIMAGINE 3 (n=274) showed 12.0% weight loss and a 2.33% HbA1c drop when added to basal insulin.
Innovent's DREAMS-3 Phase 3b head-to-head trial of mazdutide versus semaglutide in Chinese adults with type 2 diabetes and obesity was presented Sunday June 7 by Linong Ji of Peking University People's Hospital. On the composite primary endpoint, 48.0% of mazdutide-treated patients reached HbA1c under 7% plus at least 10% body weight reduction versus 21.0% on semaglutide. The readout is the first Phase 3 head-to-head defeat for semaglutide outside Lilly's tirzepatide series.
The first Phase 3 retatrutide diabetes trial, TRANSCEND-T2D-1, was simultaneously published in The Lancet and presented at the June 6 symposium. In adults with type 2 diabetes inadequately controlled on lifestyle alone, retatrutide produced A1C reductions of up to 2.0 percentage points and weight loss of up to 16.8% (36.6 lbs) at 40 weeks, with up to 46% achieving a normal A1C — a threshold rare in diabetes treatment trials. Systolic blood pressure and lipid markers improved across doses.
At ADA 2026, Novo Nordisk reported full Phase 3 REIMAGINE 2 data for CagriSema (cagrilintide plus semaglutide fixed-dose combination) in 2,728 adults with type 2 diabetes inadequately controlled on metformin with or without an SGLT2 inhibitor. Over 68 weeks, CagriSema 2.4 mg/2.4 mg produced superior HbA1c reduction of 1.91 percentage points and 14.2% mean weight loss, both better than the semaglutide 2.4 mg, cagrilintide 2.4 mg, and placebo comparator arms. The readout is the first head-to-head Phase 3 win for the dual amylin/GLP-1 combination over its individual components.
Kailera Therapeutics and Hengrui Pharma reported positive topline Phase 3 data from a Chinese T2D trial of HRS-7535, an oral small-molecule GLP-1 receptor agonist licensed to Kailera. Most adverse events were mild-to-moderate GI, with no Grade 3 hypoglycemic events and no liver-safety signal. Hengrui plans to submit a Chinese NDA for HRS-7535 in T2D and will share detailed efficacy data at an upcoming scientific conference. The readout extends the China-led oral-GLP-1 pipeline alongside ribupatide and aleniglipron.
Eli Lilly will present full data on retatrutide, Foundayo (orforglipron), and Mounjaro at the American Diabetes Association's 86th Scientific Sessions. The triple agonist retatrutide lowered A1C by up to 2.0% and drove 16.8% weight loss, about 36.6 lbs at the 12 mg dose, over 40 weeks in its first Phase 3 diabetes trial, TRANSCEND-T2D-1. Oral Foundayo beat oral semaglutide head-to-head with 73.6% greater relative weight loss and an A1C reduction of up to 1.7% against 0.8% for dapagliflozin.
A separate ASCO 2026 analysis examined outcomes in patients with breast cancer and co-existing obesity or type 2 diabetes who received GLP-1 receptor agonists — adding breast-cancer-specific depth to the broader GLP-1-and-cancer signal that ran through the meeting. The analysis sits alongside Abstract 3143 (the 12,112-patient study showing 38-50% lower metastatic progression across four obesity-related cancers, with breast cancer at 10% vs 20% metastasis on GLP-1 vs gliptin) and the Roswell Park aggressive-breast-cancer analysis. The consistent theme across the ASCO 2026 GLP-1 oncology slate: in obesity-related and metabolically-driven cancers, GLP-1 therapy appears associated with better outcomes, with the strongest and most mechanistically interpretable signal in breast cancer where high tumor GLP-1 receptor expression tracked with 45% lower mortality. Adverse-event rates matched the comparator groups with no increase in pancreatitis or other GLP-1-associated concerns in the cancer setting. The data is observational and not yet RCT-grade, but the breast-cancer consistency across multiple independent analyses strengthens the case for prospective study.
A Frontiers in Endocrinology multicenter retrospective cohort study (2026) reports real-world safety and effectiveness of semaglutide in patients with type 2 diabetes and end-stage renal disease — the population systematically excluded from FLOW (which capped at eGFR ≥ 25) and the SELECT pre-specified kidney composite analysis. ESRD patients comprise roughly 1% of the diabetic population but 7% of US healthcare spending; their cardiovascular event rates are among the highest documented. The cohort fills a clinical gap: prescribers managing dialysis-dependent patients have had to extrapolate from outcome trials that explicitly excluded the population. Work joins the SOUL oral-semaglutide CKD analysis as the fastest-growing GLP-1 evidence stream beyond obesity and T2D.
On the April 30 Q1 2026 call, Eli Lilly disclosed positive topline results from TRANSCEND T2D1, the first Phase 3 trial of retatrutide (triple GLP-1/GIP/glucagon agonist) in adults with type 2 diabetes. Compared with placebo, retatrutide lowered A1c by an average of 1.7 to 2.0 percentage points across doses and produced mean weight loss of 11.1 to 16.6 kilograms (25 to 37 pounds). The data complement the previously reported TRIUMPH-4 obesity-with-knee-osteoarthritis results (28.7% weight loss, 75.8% pain reduction). TRIUMPH-1, an 80-week obesity study, is the next retatrutide readout expected, with seven additional Phase 3 readouts still to come in 2026 ahead of a planned regulatory submission late 2026 or 2027.
Novo Nordisk announced May 1 that Ozempic (semaglutide) tablets at 1.5 mg, 4 mg, and 9 mg will be available across 70,000+ U.S. pharmacies starting Monday, May 4, for adults with type 2 diabetes. The product is the only FDA-approved oral peptide GLP-1 medication cleared for both primary and secondary cardiovascular risk reduction in adults with T2D, manufactured end-to-end in the United States. Insured patients can access the pill for as little as $25 for up to a 3-month supply; self-pay patients face $149–$299/month depending on dose strength.
WeightWatchers announced May 1 that its Med+ platform and affiliated medical groups will begin offering Ozempic pill (oral semaglutide) for clinically eligible members with type 2 diabetes. Many eligible members can access the medication for as low as $25/month with pharmacy benefits. The expansion adds a once-daily oral GLP-1 alongside the existing Med+ portfolio of clinically supervised weight-management and metabolic-health treatments, giving WW a foothold in T2D care to complement its weight-loss positioning.
Eli Lilly announced positive topline results from ACHIEVE-4, the longest Phase 3 study of Foundayo (orforglipron) to date in 2,700+ adults with type 2 diabetes across 15 countries. The pre-planned analysis showed a 57% lower risk of all-cause death (HR 0.43, p=0.002), while meeting non-inferiority for the prespecified cardiovascular endpoint (HR 0.84). Lilly plans to submit Foundayo for type 2 diabetes to the FDA by end of Q2.
Retatrutide met its primary endpoint of superior A1C reduction and all key secondary endpoints at 40 weeks compared with placebo in type 2 diabetes patients, also demonstrating significant weight loss.
Eli Lilly's triple agonist (GIP/GLP-1/glucagon) retatrutide met its primary A1C reduction endpoint and all key secondary endpoints at 40 weeks in the TRANSCEND-T2D-1 trial.