Semaglutide, tirzepatide equally effective in cardiometabolic HFpEF

Semaglutide is as good as tirzepatide in the treatment of patients with cardiometabolic heart failure with preserved ejection fraction (HFpEF), with both drugs yielding substantial reduction in the risks of cardiac hospitalization and mortality compared with sitagliptin, as reported in a study.

Researchers constructed active-comparator, new-user cohort studies using national US healthcare claims data. To benchmark results, two cohort studies emulating the STEP-HFpEF DM (semaglutide) and SUMMIT (tirzepatide) trials were established. Then, the eligibility criteria were expanded to include patients typically treated in clinical practice. Finally, tirzepatide was directly compared with semaglutide to see which drug performed better. Sitagliptin was used as a placebo proxy.

The composite of hospitalization for heart failure and all-cause mortality was the primary endpoint. Proportional hazards models fitted with propensity score weighting and adjusted for a comprehensive set of pretreatment patient characteristics were used in the analyses.

Benchmarking of the two trial emulations showed high agreement on all prespecified metrics. In analyses using expanded eligibility criteria, 58,333 patients were included in the semaglutide vs sitagliptin cohort, 11,257 for the tirzepatide vs sitagliptin cohort, and 28,100 for the tirzepatide vs semaglutide cohort.

Over a follow-up of up to 52 weeks, the risk of the composite of hospitalization for heart failure and all-cause mortality was substantially lower among semaglutide users (hazard ratio [HR], 0.58, 95 percent confidence interval [CI], 0.51–0.65) and tirzepatide users (HR, 0.42, 95 percent CI, 0.31–0.57) relative to sitagliptin users.

In the head-to-head comparison, tirzepatide showed no meaningful benefit over semaglutide in terms of the primary endpoint (HR, 0.86, 95 percent CI, 0.70–1.06).

Results were consistent for across negative control, secondary endpoint, subgroup, and sensitivity analyses.

There was no evidence of a substantial increase in risk across select safety measures.