Home · Health · Sep 30 archive
Tirzepatide Shows Promise Beyond Cardiovascular Benefits
Developing
In Short: At the European Association for the Study of Diabetes (EASD) 2026 Annual Meeting, new analyses from the SURPASS-CVOT trial indicated that tirzepatide may offer benefits beyond traditional cardiovascular outcomes for patients with type 2 diabetes and established cardiovascular disease.
The trial, which randomized 13,299 adults to either tirzepatide or dulaglutide, found that all-cause mortality was lower with tirzepatide compared to dulaglutide (HR, 0.84; 95% CI, 0.75-0.94). Noncardiovascular mortality was also lower (HR, 0.76; 95% CI, 0.63-0.91; nominal P =.003), but there was no clear difference in cardiovascular mortality.
Session moderator Naveed Sattar, MD, PhD, highlighted the importance of considering infection, quality of life, and kidney outcomes in addition to cardiovascular effects.
Stefano Del Prato, MD, presented findings showing that tirzepatide produced greater reductions in A1c and body weight compared to dulaglutide, potentially contributing to improved immune function and better glycemic control.
Patient-reported outcomes, including the EQ-5D-5L health status index and the Impact of Weight on Self-Perception questionnaire, also showed improvements with tirzepatide.
The discussion at the meeting centered on whether the benefits of incretin-based therapies should be increasingly considered beyond conventional cardiovascular and metabolic outcomes.
What this adds
The specific mechanisms by which tirzepatide reduces infection-related mortality are still under investigation, with potential factors including improved immune function, better glycemic control, and enhanced blood flow within adipose tissue.
What's still developing
- "I think we've been cardiovascular-centric," said session moderator, Naveed Sattar, MD, PhD, professor of cardiometabolic medicine at the University of Glasgow, Scotland, highlighting infection, quality of life, and kidney outcomes among effects that also matter to patients.
- Discussing the findings, Samuel Klein, MD, of Washington University School of Medicine in St Louis, questioned whether the lower infection-related mortality observed with tirzepatide could reflect improved immune function accompanying greater weight loss, better glycemic control, or potentially improved blood flow within adipose tissue as fat mass decreases.
- Klein noted that obesity is characterized by increased immune activity and inflammation but, paradoxically, reduces effectiveness of the immune system in combating viral, bacterial, and fungal infections.
- MILAN —New analyses from the SURPASS-CVOT trial suggest that differences between tirzepatide and dulaglutide in people with type 2 diabetes (T2D) and established cardiovascular disease (CVD) may extend beyond traditional cardiovascular outcomes, with signals emerging in favor of tirzepatide for lower noncardiovascular mortality and improvements in patient-reported health and daily functioning.
- SURPASS-CVOT randomized 13,299 adults with T2D and established atherosclerotic CVD to tirzepatide (2.5 mg titrated up to a maximum of 15 mg) or dulaglutide 1.5 mg once weekly, on top of standard care.
- The primary analysis previously showed that tirzepatide was noninferior, but not superior, to dulaglutide — an established GLP-1 receptor agonist with demonstrated cardiovascular benefit for the primary three-point major adverse cardiovascular events (MACE) endpoint.
- MACE occurred in 801 of 6586 participants (12.2%) receiving tirzepatide and 862 of 6579 (13.1%) receiving dulaglutide (hazard ratio [HR], 0.92; 95% CI, 0.83-1.01; P =.003 for noninferiority and P =.09 for superiority).
- In one of the current analyses of the trial, presented at the meeting by Stefano Del Prato, MD, professor of endocrinology at Sant'Anna School of Advanced Studies, Pisa, Italy, researchers looked at differences in time to cardiovascular death, time to death of any cause, and rates of noncardiovascular mortality, among other secondary endpoints.
- The difference in noncardiovascular mortality appeared largely attributable to infection-related deaths.