Written By: Pharmacally medical News Desk
The New England Journal of Medicine has published results from the SURPASS-CVOT trial (NCT04255433), a landmark cardiovascular outcomes study evaluating tirzepatide in people with type 2 diabetes and established atherosclerotic cardiovascular disease.
The trial used dulaglutide as the comparator, a GLP-1 receptor agonist already proven to reduce cardiovascular events. This design set a high bar: tirzepatide had to perform against a therapy with an established heart-protective profile, not placebo.
Over follow-up, the primary composite endpoint occurred in 12.2% of patients on tirzepatide compared to 13.1% of patients on dulaglutide. This translated to a hazard ratio of 0.92, meeting the prespecified threshold for non-inferiority, though not superiority. In practice, this means tirzepatide did not increase cardiovascular risk when compared with a drug already known to protect the heart.
On metabolic advantages front patients treated with tirzepatide achieved greater HbA1c reductions and more weight loss. These signals suggesting slower kidney function decline and numerically fewer deaths were observed, but these remain exploratory and require further evaluation.
On safety standpoint; both therapies showed class-consistent safety. Gastrointestinal events such as nausea and diarrhea were reported more frequently with tirzepatide, especially during dose escalation. Serious adverse events were similar between study groups.
SURPASS-CVOT was a randomized, double-blind trial enrolling more than 13,000 adults with type 2 diabetes and confirmed cardiovascular disease. Participants received once-weekly tirzepatide or dulaglutide. The primary endpoint was a composite of cardiovascular death, myocardial infarction, or stroke. Investigators aimed to determine whether tirzepatide was at least as effective as dulaglutide in preventing these major cardiovascular events.
Lead investigator Stephen Nicholls, MD emphasized that these findings help reinforce confidence in tirzepatide’s cardiovascular profile. He highlighted that the data support expanding treatment choices for people with diabetes who also face high cardiovascular risk, noting that the non-inferiority result provides reassurance when considering tirzepatide in routine practice.
Nicholls framed the results as an important validation step, underscoring that broader access and thoughtful integration into diabetes care will now become key priorities.
Because dulaglutide already has proven cardiovascular benefit, demonstrating non-inferiority against it is notable. Tirzepatide brings potent glycaemic and weight-reduction effects without compromising cardiovascular safety, positioning it as a strong option in cardiometabolic management.
Future analyses from SURPASS-CVOT are expected to explore subgroup responses and potential long-term patterns. While these results could inform label discussions, any regulatory movement will depend on agency review of the complete dataset, including ongoing safety monitoring and complementary evidence from the broader SURPASS program.
In summary, tirzepatide matched dulaglutide in reducing the risk of cardiovascular death, heart attack, or stroke in people with high-risk type 2 diabetes, while maintaining its metabolic advantages. The findings advance tirzepatide from a promising glucose-lowering therapy to one with validated cardiovascular reassurance, and they are likely to influence treatment decisions moving forward.
References
Stephen J. Nicholls et al, Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes, N Engl J Med 2025;393:2409-2420, DOI: 10.1056/NEJMoa2505928
SURPASS-CVOT Published: Large Trial Confirms CVD Efficacy of Tirzepatide, 18 December 2025, https://www.tctmd.com/news/surpass-cvot-published-large-trial-confirms-cvd-efficacy-tirzepatide?utm_source=chatgpt.com