GLP-1 Receptor Agonist Use Reduces Heart Failure Mortality
Losing weight improves health outcomes. To put it another way, carrying excess visceral fat tissue causes ongoing harm via a range of mechanisms connected to the disrupted, inflammatory metabolism it induces. Thus a growing number of studies demonstrate that weight loss achieved through GLP-1 receptor agonist use improves outcomes in the presently largely overweight populations of the wealthier regions of the world. It is always possible that GLP1-1 receptor agonist drugs have other effects that are meaningful along the way, but losing weight is so influential on health that very robust data would have to be presented to be convincing that non-weight-loss effects are important in the context of overweight individuals.
Heart failure with preserved ejection fraction (HFpEF) is a major cause of hospitalization, often occurring in patients with cardiometabolic comorbidities such as obesity and type 2 diabetes. Although early trials of semaglutide and tirzepatide have shown promising results in improving symptoms, those findings were based on few clinical events, leaving treatment recommendations uncertain.
To evaluate the effectiveness and safety of semaglutide and tirzepatide in patients with cardiometabolic HFpEF in clinical practice, five cohort studies were assessed using national US health care claims data from 2018 to 2024. Two cohort studies emulated the STEP-HFpEF DM (semaglutide) and SUMMIT (tirzepatide) trials to benchmark results. Eligibility criteria were then expanded to evaluate treatment effects in patients typically treated in clinical practice. Finally, a head-to-head comparison of tirzepatide and semaglutide was implemented. Follow-up was up to 52 weeks.
The primary end point was a composite of hospitalization for heart failure or all-cause mortality. In analyses using expanded eligibility criteria, 58,333 patients were included in the semaglutide vs sitagliptin cohort, 11,257 for tirzepatide vs sitagliptin, and 28,100 for tirzepatide vs semaglutide. Initiators of semaglutide (hazard ratio, HR, 0.58) and tirzepatide (HR, 0.42) had substantially lower risk of the primary end point compared with sitagliptin. Tirzepatide had no meaningfully lowered risk compared with semaglutide (HR, 0.86).