Written by Peter Liu
Spoon Feed
Tirzepatide is one of two GLP1-agonists that appears to decrease heart failure (HF) hospitalizations and improve quality of life for patients with obesity and HF with preserved ejection fraction (HFpEF).
GLP1 agonists join SGLT2 inhibitors and mineralocorticoid antagonists as effective medications in HFpEF
Not long ago, medical treatment for HFpEF was limited to diuretics and mineralocorticoid antagonists (MRA) like spironolactone. Spironolactone has risky side effects like hyperkalemia and renal dysfunction, as well as controversy from geographic differences in results and protocol adherence in TOPCAT. Now, trials like this one, the SUMMIT trial, are showing effective new medications for HFpEF with similar benefits to MRAs and potentially less risky side effect profiles.
The SUMMIT trial was a multicenter, double-blind, randomized, placebo-controlled trial assigned 731 patients (1:1) to receive tirzepatide (up to 15 mg weekly) or placebo for at least 52 weeks. Patients had heart failure with EF>50% and BMI>30. Primary endpoints were a composite of cardiovascular death or worsening HF events over 2 years of follow-up and a change in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) over one year. Tirzepatide reduced heart failure hospitalizations (HR 0.44, 0.22 to 0.87) and improved quality of life (KCCQ-CSS change of 19.5±1.2 vs. 12.7±1.3, difference 6.9, 3.3-10.6, p<0.001). Patients also had greater improvements in 6-minute walk distance (difference of 18.3 meters, 9.9-16.7, p<0.001) and greater weight loss ( −11.6%. −12.9 to −10.4, p<0.001). Discontinuations due to adverse events were higher with tirzepatide (6.3% vs. 1.4%), mainly due to gastrointestinal side effects. Notably, these findings mirror similar studies on semaglutide, another GLP1 agonist showing positive HFpEF outcomes.
These findings indicate benefit in heart failure outcomes with tirzepatide or semaglutide in patients with HFpEF.
How does this change my practice?
While SGLT2 inhibitors appear to have the broadest indication for use in HFpEF, I am excited to also add GLP1 agonists to the therapeutic arsenal for patients with HFpEF and obesity. Which drug class I use – MRA, SGLT2, or GLP1 – will come down to cost and insurance approval, but I am excited to have multiple options now.
Source
Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med. 2025 Jan 30;392(5):427-437. doi: 10.1056/NEJMoa2410027. Epub 2024 Nov 16. PMID: 39555826
