New head-to-head real-world study shows semaglutide outperforms dulaglutide in reducing major cardiovascular events

Novo Nordisk has reported results from the REACH study, presented at the European Association for the Study of Diabetes (EASD) 2025 Annual Meeting, offering the first head-to-head real-world comparison of once-weekly semaglutide (Ozempic^®) and dulaglutide in US Medicare patients with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD).

The REACH study found that Ozempic was associated with a 23% lower risk of major adverse cardiovascular events (MACE), including heart attack, stroke, or death, compared with dulaglutide in older adults with type 2 diabetes and ASCVD. It also demonstrated a 26% reduction in all-cause mortality and a 25% lower risk of an expanded five-point MACE that included hospitalization for unstable angina or heart failure. These results represent the first direct real-world comparison of cardiovascular outcomes between two GLP-1 receptor agonists in a Medicare population.

The analysis, presented at EASD and titled "Comparative effectiveness of once-weekly semaglutide versus dulaglutide on cardiovascular outcomes in US Medicare beneficiaries with type 2 diabetes and atherosclerotic cardiovascular disease," used 100% Medicare fee-for-service claims to ensure broad representation of older adults with multiple comorbidities. Researchers applied a target trial emulation framework to approximate the design of a randomized controlled trial and applied 1:1 propensity score matching, resulting in two treatment cohorts of 29,168 patients each, all aged 66 years or older with type 2 diabetes and ASCVD who initiated once-weekly semaglutide or dulaglutide. Outcomes were assessed over an average follow-up of 12–13 months using survival analyses, with multiple definitions of MACE and extensive sensitivity analyses applied to confirm the consistency and robustness of the results.

“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,” said Filip Krag Knop, senior vice president and incoming chief medical officer at Novo Nordisk.

“This is great news for older patients as well as healthcare professionals, as these results build on the importance of our randomised clinical trial data assessing the effectiveness of treatments in a real-life setting. This also supports what we already know from our clinical development programmes that not all GLP-1 RAs are the same.”

According to the authors, these results provide the first direct real-world comparative evidence between GLP-1 receptor agonists in this high-risk population, complementing existing randomised trial data such as SUSTAIN-6 for semaglutide and REWIND for dulaglutide. The researchers concluded:

“Among US Medicare beneficiaries with T2D and ASCVD, once-weekly semaglutide was associated with reduced risks of CV outcomes, including a 23% risk reduction in 3-point MACE and a 26% risk reduction in all-cause death, compared to dulaglutide. These findings address a critical evidence gap that informs important treatment decisions for clinicians and policymakers, particularly amid rising GLP-1 RA use and ongoing Medicare price negotiations.”