Key result
Tirzepatide in men linked to ~13% fewer hospitalizations vs women in obese HFpEF.
Why the study?
Sex-related differences are recognized in HFpEF, but real-world data describing clinical outcomes by sex among patients with obesity and HFpEF treated with tirzepatide remain limited.
Does tirzepatide therapy result in different rates of all-cause hospitalization and clinical outcomes between male and female patients with obesity and HFpEF?
Cohort (n=3,308)
Yes
Does tirzepatide therapy result in different rates of all-cause hospitalization and clinical outcomes between male and female patients with obesity and HFpEF?
Among patients with obesity and HFpEF treated with tirzepatide, males had a modestly lower risk of all-cause hospitalization and reported less nausea and vomiting than females, though major cardiovascular outcomes were similar.
Answers are grounded in this paper and cite their sources.
May suggest sex differences in tirzepatide hospitalization risk among obese HFpEF patients; hypothesis-generating and should not yet change practice.
BackgroundSex-related differences are well recognized in heart failure with preserved ejection fraction (HFpEF), but real-world data describing clinical outcomes by sex among patients with obesity and HFpEF treated with tirzepatide remain limited.ObjectivesTo compare observed hospitalization, cardiovascular, and gastrointestinal outcomes between male and female patients with obesity and HFpEF treated with tirzepatide.DesignRetrospective, propensity score-matched, within-treatment cohort study.MethodsA retrospective study was conducted using TriNetX database which included 110 healthcare organizations. Adults with obesity, HFpEF, and taking tirzepatide between June 1, 2022 and January 1, 2025 were identified. Males and females were balanced using 1:1 propensity score matching (n=1,654 per group). Primary outcome assessed included all-cause hospitalization. Secondary outcomes were all-cause mortality, HF exacerbation, major adverse cardiovascular events (MACE), incident atrial fibrillation, nausea/vomiting and diarrhea. Two prespecified falsification endpoints were used.ResultsDuring 1-year follow-up, males had a lower hazard of all-cause hospitalization compared with females (HR 0.87, 95% CI 0.77-0.98). No significant differences were observed for all-cause mortality (HR 1.73, 95% CI 0.95-3.18), HF exacerbation (HR 1.14, 95% CI 0.90-1.44), MACE (HR 1.28, 95% CI 0.99-1.65), or incident atrial fibrillation (HR 1.21, 95% CI 0.61-2.43). Males experienced lower rates of nausea and vomiting (HR 0.50, 95% CI 0.37-0.67), while diarrhea was similar (HR 0.84, 95% CI 0.59-1.19). Falsification endpoints showed no significant associations.ConclusionAmong tirzepatide-treated patients with obesity and HFpEF, no statistically significant sex-associated differences were detected in major cardiovascular outcomes. Males had a modestly lower observed hazard of hospitalization and fewer coded nausea and vomiting events. Because this was a within-treatment observational comparison without an external comparator, these findings should not be interpreted as evidence of differential tirzepatide effectiveness by sex.
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Mortada et al. (2026) conducted a cohort in Obesity and Heart Failure with Preserved Ejection Fraction (HFpEF) (n=3,308). Male sex vs. Female sex was evaluated on All-cause hospitalization (HR 0.87, 95% CI 0.77-0.98, p=0.026). Male patients with obesity and HFpEF treated with tirzepatide had a significantly lower hazard of all-cause hospitalization compared with female patients (HR 0.87, 27.1% vs 32.2%).
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