Semaglutide, tirzepatide showed improved outcomes in patients with HF and diabetes
Risk for heart failure (HF) hospitalization or all-cause mortality was more than 40% lower in patients with type 2 diabetes and HF with preserved ejection fraction who took semaglutide or tirzepatide compared to those who took sitagliptin (a placebo proxy), a study found.
Taking semaglutide or tirzepatide may substantially reduce risk for poor outcomes in patients who have cardiometabolic heart failure with preserved ejection fraction (HFpEF), a recent study found.
Clinical trials have found that semaglutide and tirzepatide improved symptoms in patients with HFpEF related to obesity and type 2 diabetes, but sample sizes were small, there were few cardiovascular outcomes, and eligibility criteria were strict. For this study, researchers developed cohorts from three national U.S. health claims databases from 2018 to 2024 to provide real-world evidence of the effectiveness and safety of these drugs for this population.
The STEP-HFpEF DM trial, which evaluated semaglutide, and the SUMMIT trial, which evaluated tirzepatide, were both emulated to benchmark the results. The researchers expanded the eligibility criteria of these trials to include patients typically seen in clinical practice and also did a direct comparison of tirzepatide and semaglutide. Sitagliptin was used as a placebo proxy. The primary end point was a composite of hospitalization for HF and all-cause mortality over a follow-up period of 52 weeks. The results were published Aug. 31 by JAMA.
Of 1,670,792 patients starting semaglutide, tirzepatide, or sitagliptin in the databases, 21,151 met the trial eligibility criteria emulating STEP-HFpEF DM and 58,333 were included in the expanded semaglutide versus sitagliptin cohort. For tirzepatide, 3,173 patients met the trial eligibility criteria emulating SUMMIT and 11,257 were included in the expanded tirzepatide versus sitagliptin cohort. Finally, 28,100 patients were included in the cohort directly comparing tirzepatide and semaglutide. Mean age across the cohorts ranged from 66.7 to 70.8 years, 53.3% to 54.7% of patients were female, and mean body mass index ranged from 36.6 kg/m2 to 40.2 kg/m2.
In analyses that used expanded eligibility criteria, patients taking semaglutide or tirzepatide had substantially lower risk of the primary end point than those taking sitagliptin (hazard ratios [HRs], 0.58 [95% CI, 0.51 to 0.65] and 0.42 [95% CI, 0.31 to 0.57], respectively). In the head-to-head comparison, the one-year risk of the primary outcome was 3.3% (95% CI, 2.8% to 3.9%) with tirzepatide and 3.4% (95% CI, 2.9% to 4.1%) with semaglutide (HR, 0.86; 95% CI, 0.70 to 1.06). Results were consistent for negative controls, secondary end points, subgroups, and sensitivity analyses, and there was no substantial difference in select safety end points.
The authors noted that their results could have been affected by residual confounding and that data on medication use were inferred from dispensing records and may not capture adherence, among other limitations.
“In this study, treatment with semaglutide or tirzepatide was associated with a more than 40% lower risk of hospitalization for heart failure or all-cause mortality compared with sitagliptin, a glucose-lowering drug shown in prior trials to have no effect on heart failure outcomes,” the authors wrote. “This aligns closely with early and underpowered evidence from randomized trials with few clinical end points, while expanded analyses in populations representative of routine care strengthen the relevance of the current findings for clinical and regulatory decision-making. The head-to-head comparison showed no meaningful difference in event rates.”