Women with obesity-related heart failure show up to the clinic sicker than men, and tirzepatide helped them just as much.
That is the finding of a prespecified secondary analysis of the SUMMIT trial, published July 7 in JACC: Heart Failure ↗. The parent trial had already shown that tirzepatide ↗, Eli Lilly's dual GIP and GLP-1 receptor agonist sold as Zepbound and Mounjaro, cut the risk of heart-failure worsening or cardiovascular death in people with obesity-related HFpEF. SUMMIT randomized 731 patients with NYHA class II to IV symptoms and a body mass index of at least 30 to either tirzepatide (364) or placebo (367). The new paper from Barry Borlaug and colleagues at the Mayo Clinic splits those patients by sex and asks whether the drug worked differently in women and men. It did not.
HFpEF is heart failure with preserved ejection fraction. The heart still squeezes with normal strength, but it has grown stiff and fills poorly, so blood backs up and patients tire and swell. It accounts for roughly half of all heart failure, and it lands harder on women, who outnumbered men in the trial (393 versus 338).
Different bodies, same disease
The two groups arrived at the disease from different directions. Women had higher body mass index and a higher waist-to-height ratio, worse symptoms (a higher NYHA functional class and a lower score on the Kansas City Cardiomyopathy Questionnaire, a 0-to-100 scale where higher means better quality of life), and poorer exercise capacity on a six-minute walk test. Men carried more of the structural damage instead: greater left ventricular remodeling and more fat packed around the heart. Put plainly, women felt worse while men's hearts looked more visibly rebuilt.
None of that changed how the drug performed.
The benefit held across sex
On the main endpoint, the combination of worsening heart failure or cardiovascular death, tirzepatide cut risk by roughly a third in both groups. The hazard ratio was 0.66 in women and 0.61 in men, and the test for a sex difference came back flat (interaction P = 0.81), meaning the small gap is noise. Symptom scores improved by 8.1 points in women and 5.5 in men after subtracting the placebo effect (interaction P = 0.43). Six-minute walk distance improved by 18 meters and 15 meters (interaction P = 0.76). Every comparison pointed the same way: consistent benefit, no meaningful split by sex.
That matters because women make up the majority of HFpEF patients and have often been the group where a cardiovascular drug's benefit turned out smaller or murkier once someone looked. Here someone looked, and the benefit was there for both.
Where sex did show up
One relationship did differ. Among patients on tirzepatide, how much weight a person lost tracked how much better they felt far more tightly in women than in men (interaction P = 0.0058). The reading is mechanistic: in women, more of the symptom relief appears to run through the weight loss itself, while in men more of it comes from something the trial did not isolate. A higher waist-to-height ratio was also tied to worse kidney function only in women (P = 0.043).
So the drug is not sex-blind in how it works, only in how much it delivers.
Tirzepatide is one of the few agents to move hard outcomes in HFpEF, a condition that spent two decades resisting almost everything cardiologists threw at it. What separates it from the GLP-1-only drugs is the second receptor: it engages both GLP-1R ↗ and GIPR ↗, the incretin pair that peptidemodel tracks as distinct targets. The SUMMIT-by-sex result does not tell us which receptor arm carries the heart-failure effect. It does tell clinicians they can prescribe the same expectation to a woman and a man who walk in with very different-looking versions of the same failing heart.