Cardiovascular data has reframed how GLP-1 drugs are positioned. SELECT was the first major trial to show MACE reduction (20%) in non-diabetic adults with obesity. Heart-failure work followed: a Mass General Brigham analysis in JAMA of 90,000+ HFpEF patients reported a 42% reduction in heart-failure hospitalization or all-cause mortality on semaglutide, and 58% on tirzepatide versus sitagliptin.
The atherosclerosis-prevention data is more preliminary but consistent. A Scientific Reports study found early intervention with tirzepatide or semaglutide reduced atherosclerotic plaque in ApoE-knockout mice; clinical follow-up is in progress. Cardiometabolic peptide candidates outside the GLP-1 family — Merck's enlicitide-decanoate (PCSK9), Takeda's rusfertide for polycythemia vera — also land here.
Stories below cover the readouts, registry data, and payer rulings.
Lilly presented the Phase 3 ACHIEVE-4 trial of its oral small-molecule GLP-1 drug Foundayo (orforglipron) at EASD on Thursday, October 1, 2026, alongside publication in The Lancet. In 2,749 adults with type 2 diabetes, overweight or obesity, and increased cardiovascular risk, Foundayo met its noninferiority goal against insulin glargine for cardiovascular death, heart attack, stroke, or hospitalization for unstable angina (MACE-4 hazard ratio 0.84; 95% CI 0.59 to 1.20); the three-part MACE-3 hazard ratio was 0.77 (95% CI 0.52 to 1.13). At 52 weeks, A1C fell 1.6 points versus 1.0 and weight fell 8.8% versus a 1.7% gain on glargine. Lilly also reported a lower rate of death from any cause (hazard ratio 0.43) but described that analysis as exploratory and not controlled for multiple comparisons; 10.6% of Foundayo patients stopped treatment because of adverse events.
Novo announced on Tuesday, September 29, 2026 results of COMPETE SWITCH CV, a retrospective analysis of U.S. claims data from Komodo Health (January 2018 to September 2025) in adults with type 2 diabetes who had been taking semaglutide 1 mg. Over up to 720 days, the 185,705 people who escalated to semaglutide 2 mg had a 6% lower adjusted risk of death, heart attack, or stroke than the 23,104 who switched to tirzepatide (adjusted hazard ratio for switching 1.06; 95% CI 1.04 to 1.08). Novo said the analysis shows an association rather than cause and effect, may carry residual confounding, and did not assess safety outcomes.
Researchers led by Karen Hvid of Copenhagen University Hospital, Herlev, are presenting at the EASD annual meeting in Milan an analysis of 313,145 adults with a BMI of 25 or higher and no coronary heart disease or diabetes, drawn from the Copenhagen General Population Study and UK Biobank and followed for up to 18 and 15 years. About 44% (Copenhagen) and 48% (UK Biobank) of people with a BMI of 25 to 26.9, who fall below current GLP-1 weight-loss eligibility, had elevated remnant cholesterol, low-grade inflammation, or both. Those with both markers and no drug indication were 41% (Copenhagen) and 47% (UK Biobank) more likely to develop heart disease than people without an indication and with healthy levels, compared with increases of 41% and 35% among people who already qualify for the drugs. The findings are observational, and the authors said clinical trials are needed.
The American College of Cardiology, American Heart Association, American Diabetes Association, and American Society of Nephrology jointly published the first-ever clinical guideline for Cardiovascular-Kidney-Metabolic (CKM) Syndrome on June 9, 2026, in Circulation and JACC. The framework establishes a standardized CKM staging system (stages 0 to 4) to identify patients earlier, personalize therapy by absolute cardiovascular risk, and promote both prevention and regression of disease. GLP-1 receptor agonists are explicitly recommended in select patients with type 2 diabetes or obesity plus other cardiovascular risk factors, alongside SGLT2 inhibitors and kidney-protective therapies. The guideline embeds the GLP-1 class into multi-society standard of care for the first time and adds clinical-society weight to the SELECT, FLOW, and ESSENCE outcomes evidence base.
The ADA closed its 86th Scientific Sessions on June 8 with a formal revision to its Standards of Care that elevates cardiovascular and kidney risk reduction to a co-primary treatment goal alongside glycemic control, ending decades of practice in which HbA1c stood as the dominant benchmark. The shift formalizes a redefinition of diabetes care around the cardio-renal-metabolic axis that GLP-1, SGLT2, and finerenone evidence has driven, and pushes earlier GLP-1 and SGLT2 use from diabetes diagnosis.
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.
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.
A study of 220,043 patients published in Diabetes, Obesity and Metabolism found that combining GLP-1 receptor agonists with SGLT2 inhibitors reduced all-cause mortality by 29%, the cardiovascular composite outcome by 19%, and heart failure risk by 22% compared to SGLT2 inhibitor use alone over 1.3 years of median follow-up.
A Mass General Brigham study of over 90,000 HFpEF patients published in JAMA found semaglutide reduced heart failure hospitalization or all-cause mortality by 42%, while tirzepatide achieved a 58% risk reduction compared with sitagliptin. Both drugs showed acceptable safety profiles with benefits appearing early in treatment.
A study in Scientific Reports found that early intervention with tirzepatide or semaglutide significantly reduced atherosclerotic plaque formation in ApoE-knockout mice, suggesting GLP-1 drugs may have preventive cardiovascular benefits beyond their metabolic effects when initiated before disease progression.
A new review highlights GLP-1 RAs achieving a 55% reduction in apnea-hypopnea index and 14.9% mean weight loss in non-diabetic populations, with pleiotropic effects across cardiovascular, renal, and skeletal systems.
The FLOW trial showed semaglutide reduced major kidney disease events by ~24%, while the SELECT trial found a 20% reduction in major adverse cardiovascular events among 17,600+ adults.
A study of ~175,000 Type 1 diabetes patients found GLP-1 receptor agonists reduced five-year cardiovascular event risk by 15% and end-stage kidney disease by 19%, with no increase in severe hypoglycemia. Published in Nature Medicine.
Under new UK guidance, GPs can prescribe semaglutide (Wegovy) to overweight patients who have had heart attacks, strokes, or serious circulation problems, expanding its use beyond weight management.
A condition-by-condition guide examining what's proven, promising, and untested for GLP-1 drugs beyond weight loss — covering cardiovascular disease, addiction, kidney disease, and neurological conditions.
The European Medicines Agency formally approved semaglutide with cardiovascular and stroke-related benefits — a first for any GLP-1 receptor agonist in Europe.