A review of evidence through 2026 finds that tirzepatide improves symptoms and reduces adipose tissue in obesity-related HFpEF, while SGLT2 inhibitors reduce heart failure hospitalizations. The authors argue the two drug classes act through complementary pathways, but note that combined use has not yet been tested in a trial.
Narrative review — Review. Population: Patients with heart failure with preserved ejection fraction and obesity. Interventions: Tirzepatide; SGLT2 inhibitors (empagliflozin).
Tirzepatide was associated with substantial weight loss (>20%), significant reductions in epicardial and paracardiac adipose tissue, and a 19.5-point improvement in Kansas City Cardiomyopathy Questionnaire scores in the SUMMIT trial. SGLT2 inhibitors, exemplified by empagliflozin, reduced heart failure hospitalization independent of diabetes status and had renal-protective effects. Because SUMMIT and EMPEROR-Preserved differed in design and populations, direct comparison between agents is not statistically valid. Combined use of tirzepatide and SGLT2 inhibitors is mechanistically promising but has not yet been tested in a dedicated randomized controlled trial.
Researchers studying tirzepatide will find it positioned as a cardiometabolic therapy in obesity-related HFpEF, with quantified effects on weight, cardiac adipose tissue, and patient-reported symptoms. The paper does not establish comparative efficacy against SGLT2 inhibitors, nor does it demonstrate safety or long-term efficacy of combining the two drug classes.
Peptide profiles: Tirzepatide.
All indexed evidence: Tirzepatide trials & papers.
Related studies: Weight Loss-Dependent Changes in Body Composition and Bone Health in People With Obesity….