Ozempic Shows Greater Effect in Reducing Stroke, Heart Attack Risk Over Competitor Dulaglutide

In a first-ever, head-to-head, real-world trial, findings showed that semaglutide (Ozempic; Novo Nordisk), an FDA-approved glucagon-like peptide 1 receptor agonist (GLP-1 RA) used for weight loss and diabetes, outperformed dulaglutide, a competitor GLP-1 RA, in lowering the risk of heart attack, stroke, and death. Regulatory action in the U.S. is expected later this year on whether the medication will gain an expanded label to cover cardiovascular risk reduction.^1,2

Semaglutide, which recently had its label expanded in Europe as the first GLP-1 RA to reduce cardiovascular death, heart attack, and stroke, led to a 26% lower risk of death versus dulaglutide. Presented at the European Association for the Study of Diabetes (EASD) 2025 Annual Meeting, held September 15-19 in Vienna, Austria, the study showed that treatment with once-weekly semaglutide was associated with a 23% reduced risk of heart attack, stroke, and death in people with type 2 diabetes and cardiovascular disease on Medicare versus dulaglutide.

The newly presented data comes from REACH, a comprehensive series of studies spanning nearly 60,000 U.S. Medicare patients living with type 2 diabetes, atherosclerotic cardiovascular disease (ASCVD). Investigators used a target trial emulation framework, enrolling 58,336 matched patients aged 66 years or older with established ASCVD to either once-weekly semaglutide or dulaglutide.

"As we age, the risk of experiencing a heart attack, stroke or dying from a cardiovascular event increases. At the same time, there are limited clinical data for people living with diabetes and cardiovascular disease aged 66 years or older. These data, showing a 23% risk reduction of a heart attack, stroke and death, fill an important gap and reinforce the well-established clinical evidence of semaglutide," Filip Krag Knop, senior vice president and incoming chief medical officer at Novo Nordisk, said in a statement.¹

Dulaglutide and semaglutide are both GLP-1 RAs used primarily in type 2 diabetes, with semaglutide also approved for chronic weight management. Both work by enhancing glucose-dependent insulin secretion, slowing gastric emptying, and reducing appetite, but they differ in structure, dosing, and breadth of indications. Dulaglutide is a once-weekly subcutaneous injection with a fixed dosing range, designed as a large GLP-1 fusion protein. Semaglutide is available in multiple formulations: once-weekly subcutaneous injection, daily oral tablets, and a higher-dose injectable for obesity.

The data presented at EASD 2025 marks the second study in less than 3 weeks demonstrating semaglutide’s superior efficacy over another GLP-1 RA in reducing heart attack and stroke. Findings from the real-world STEER study showed that semaglutide had a 57% greater risk reduction in these instances, as well as cardiovascular-related death or death from any cause, than tirzepatide, an approved medication for diabetes, weight loss, and obstructive sleep apnea.³

STEER, a retrospective, observational trial, tested the efficacy of semaglutide 2.4 mg (n = 10,625) vs tirzepatide (n = 10,625) for the prevention of (major adverse cardiovascular events (MACE) in adults with overweight or obesity and established cardiovascular disease (CVD) with no prior history of diabetes. During an average follow-up of 3.8 months with semaglutide and 4.3 months with tirzepatide, 15 cardiovascular events (0.1%) occurred in the semaglutide group compared with 39 events (0.4%) in the tirzapatide group.

Presented at the European Society of Cardiology Congress (ESC), findings showed that semaglutide treatment reduced the combined risk of heart attack, stroke, and death by 29% compared with tirzepatide, regardless of treatment gaps. The data were based on an average follow-up of 8.3 months for semaglutide and 8.6 months for tirzepatide.

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The REACH findings are only the latest to support semaglutide’s ability to treat heart problems, a leading cause of disability and death in people living with type 2 diabetes. Regarding the latest data, Knop added, "This is great news for older patients as well as healthcare professionals, as these results build on the importance of our randomized clinical trial data assessing the effectiveness of treatments in a real-life setting. This also supports what we already know from our clinical development programs that not all GLP-1 RAs are the same."¹

Additional data from REACH revealed a 25% reduced risk for heart attack, stroke, hospitalization for unstable angina or heart failure, and death from any cause in semaglutide-treated patients. Of note, death from any cause was assessed through a 5-point MACE scale.

Less than a week ago, the European Medicines Agency’s Committee for Medicinal Products for Human Use approved an update to semaglutide’s label, allowing the GLP-1 RA to be used as a medication to lower cardiovascular death, heart attack, and stroke. With the decision, it became the only oral GLP-1 RA with proven blood glucose and body weight reduction, as well as cardiovascular benefits.³

The decision to expand its indication was backed by the phase 3 SOUL trial (NCT03914326), a large-scale study of 9650 patients 50 years or older with type 2 diabetes, and known ASCVD, CKD, or both. In the study, patients on once-daily oral semaglutide, followed up over a mean of 47.5 (±10.9) months, had a 14% reduced cardiovascular death, heart attack, and stroke vs those on placebo, when added to the standard of care. Published in the New England Journal of Medicine, 12% of semaglutide-treated patients experienced the primary outcome event, a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, compared with 13.8% of those on placebo (HR, 0.86; 95% CI, 0.77-0.96; P =.006).⁴

REFERENCES
1. Novo Nordisk A/S: Ozempic® reduces the risk of heart attack, stroke and death by 23% compared to dulaglutide in the first head-to-head real-world study. News release. Novo Nordisk. September 18, 2025. Accessed September 22, 2025. https://www.globenewswire.com/news-release/2025/09/18/3152202/0/en/Novo-Nordisk-A-S-Ozempic-reduces-the-risk-of-heart-attack-stroke-and-death-by-23-compared-to-dulaglutide-in-the-first-head-to-head-real-world-study.html
2. EU approval makes Novo Nordisk’s oral semaglutide the first and only oral GLP-1 RA to reduce cardiovascular death, heart attack and stroke. News release. Novo Nordisk. September 15, 2025. Accessed September 22, 2025. https://www.globenewswire.com/news-release/2025/09/15/3149955/0/en/EU-approval-makes-Novo-Nordisk-s-oral-semaglutide-the-first-and-only-oral-GLP-1-RA-to-reduce-cardiovascular-death-heart-attack-and-stroke.html
3. Novo Nordisk’s Wegovy® cuts risk of heart attack, stroke or death by 57% compared to tirzepatide in real-world study of people with obesity and cardiovascular disease. News release. Novo Nordisk. August 31, 2025. Accessed September 22, 2025. https://www.globenewswire.com/news-release/2025/08/31/3141900/0/en/Novo-Nordisk-s-Wegovy-cuts-risk-of-heart-attack-stroke-or-death-by-57-compared-to-tirzepatide-in-real-world-study-of-people-with-obesity-and-cardiovascular-disease.html
4. McGuire DK, Marx N, Mulvagh SL, et al. Oral semaglutide and cardiovascular outcomes in high-risk type 2 diabetes. NEJM. 2025;392(20);2001-2012. doi:10.1056/NEJMoa2501006