# Tirzepatide in HFpEF by Sex: SUMMIT Trial Results in Women and Men | This GLP A prespecified SUMMIT analysis found tirzepatide's benefit in obesity-related HFpEF did not differ by sex (HR 0.66 vs 0.61), while weight loss tracked symptom improvement more closely in women. Publisher: This GLP Editorial Team Canonical: https://thisglp.com/research/same-benefit-different-route-by-sex Updated: 2026-09-18 Published: 2026-09-17 [← Research](https://thisglp.com/research) Evidence # Tirzepatide in HFpEF by Sex: SUMMIT Trial Results in Women and Men Every treatment-effect comparison by sex in SUMMIT came back null. The one significant interaction was about how the benefit arrives, not who receives it. [This GLP Editorial Team](https://thisglp.com/about)September 20267 min readUpdated September 2026 SUMMIT, 731 patients with HFpEF and obesity · Did the benefit differ by sex? · HR 0.66 (women) vs 0.61 (men) · interaction P = 0.81 — no · Did weight loss track symptom relief differently? · more closely in women · interaction P = 0.0058 — yes · Same destination, apparently different road. **Research, not medical advice.** This GLP is independent and educational. Nothing here is a substitute for individualized care from a licensed clinician, and reading it creates no doctor–patient relationship. Talk to your own provider before starting, stopping, or changing any medication, peptide, or therapy. See our [methodology](https://thisglp.com/methodology) and [terms](https://thisglp.com/terms). ## Key takeaways - A prespecified secondary analysis of the SUMMIT trial split its 731 participants by sex: 393 women and 338 men with obesity-related heart failure with preserved ejection fraction. - The effect on cardiovascular death or worsening heart failure did not differ (HR 0.66 in women, 0.61 in men, interaction P = 0.81), nor did symptom score or walking distance. - Among those taking tirzepatide, weight loss was more strongly associated with symptom improvement in women than men (interaction P = 0.0058). - Women and men differed substantially at baseline: women had higher BMI and worse symptoms, men more left ventricular remodeling and paracardiac fat. Women outnumber men in heart failure with preserved ejection fraction, and the way body fat relates to the disease is not the same in both. A prespecified analysis of the SUMMIT trial asked whether tirzepatide works differently in each [\[1\]](https://thisglp.com/research/same-benefit-different-route-by-sex#ref-1). The trial's main result is covered in [the heart failure composite](https://thisglp.com/research/tirzepatide-heart-failure-composite). The starting points really were different. Women had greater BMI, a higher waist-to-height ratio, worse symptoms on the Kansas City questionnaire, more severe functional class and shorter six-minute walk distances. Men had more left ventricular remodeling and more fat deposited around the heart. Higher waist-to-height ratio was associated with poorer kidney function in women only (interaction P = 0.043). Despite all that, the drug behaved identically. Cardiovascular death or worsening heart failure gave hazard ratios of 0.66 in women and 0.61 in men with an interaction P of 0.81. Symptom scores improved by 8.1 and 5.5 placebo-corrected points (interaction P = 0.43), and walking distance by 18 and 15 meters (interaction P = 0.76). Because sex was a planned analysis rather than one dredged up afterwards, those nulls carry real weight. One interaction did reach significance, and it is about mechanism Among participants taking tirzepatide, how much weight someone lost was more tightly linked to how much better they felt in women than in men (interaction P = 0.0058). That is not a claim that women benefited more — the benefit was the same. It suggests the benefit may arrive by a different route in each: more through weight reduction in women, more through something else in men. If that holds up it has a practical edge. In a man with this condition, a modest weight response would not necessarily predict a modest symptom response, so stopping early because the scale is disappointing could mean stopping something that was working. In a woman the scale tracks the symptoms more closely. That is a hypothesis from one trial and not a prescribing rule, and it is the kind of finding that needs replication before anyone acts on it — the same caution applied in [the semaglutide and tirzepatide comparison](https://thisglp.com/research/bigger-relative-smaller-absolute) and [the frailty analysis](https://thisglp.com/research/frailty-did-not-change-the-answer), which similarly found no heterogeneity where people expected some. The broader point is worth keeping. Subgroup analyses usually get attention when they find a difference, and this one is more useful for what it failed to find: a disease that looks different in women and men responded to the same drug in the same way, which is a reason to treat rather than to hesitate. The body composition differences underlying it connect to [what these drugs do to muscle](https://thisglp.com/research/muscle-loss-on-glp1). ## Frequently asked Does tirzepatide work better for women or men with heart failure? Neither. Hazard ratios were 0.66 in women and 0.61 in men with an interaction P of 0.81, and symptom and walking outcomes showed no heterogeneity either. What was the one significant difference? Among people taking tirzepatide, weight loss was more strongly associated with symptom improvement in women than in men. That concerns how the benefit arrives rather than how large it is. Did women and men start out the same? No. Women had higher BMI, worse symptoms and shorter walking distance, while men had more left ventricular remodeling and more fat around the heart. ## Sources 1. \[1\] Borlaug BA, Zile MR, Kramer CM, Litwin SE, et al. (2026). Effects of Tirzepatide in Obesity-Related HFpEF by Sex: A Prespecified Secondary Analysis From the SUMMIT Trial JACC: Heart Failure. [PMID 42417681](https://pubmed.ncbi.nlm.nih.gov/42417681/) ## Where to get it ### Best GLP-1 injections Every injectable seller we can verify, with the price each one publishes and an honest read of what the trials measured. [Compare providers →](https://thisglp.com/best/compounded-semaglutide) ## More in Evidence - [ 150 minutes · Weekly activity goal · 2 days · Muscle strengthening · Adapt · Symptoms and ability ### Exercise on Ozempic: Building Strength Without Ignoring Symptoms ](https://thisglp.com/research/exercise-on-ozempic) - [ STEP 1, semaglutide 2.4 mg vs placebo, % change at 68 weeks · LDL cholesterol · −2.5% vs +1.3% · Total cholesterol · −3.3% vs +0.1% · HDL cholesterol · +5.2% vs +1.4% · Triglycerides · −21.9% vs −7.3% · Wegovy label, Table 13. Adults without diabetes. Ozempic doses are lower. ### Does Ozempic Lower Cholesterol? 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