AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Five-Year Cardiovascular Outcomes of Tirzepatide in Women with Polycystic Ovarian Syndrome and Type 2 Diabetes Mellitus Receiving Metformin
By Ong TE, Koo TH, Tan DHC et al.
Background: Polycystic ovarian syndrome (PCOS) is associated with insulin resistance, type 2 diabetes mellitus (T2DM), and adverse cardiovascular risk profiles. Although tirzepatide has demonstrated cardiometabolic benefit in T2DM, its effects in women with PCOS and T2DM receiving metformin remain unclear. We evaluated five-year cardiovascular outcomes associated with tirzepatide use in this high-risk population. Hypothesis: Tirzepatide use would be associated with improved five-year cardiovascular outcomes among women with PCOS and T2DM receiving metformin. Methods: Using the TriNetX network, we identified patients aged ≥18 years with PCOS and T2DM who were receiving metformin. Patients were stratified into (1) tirzepatide and (2) no tirzepatide groups, with tirzepatide exposure defined after metformin initiation. Patients with prior coronary revascularization, acute myocardial infarction, chronic kidney disease, left ventricular ejection fraction ≤35%, or estimated glomerular filtration rate ≤30 mL/min/1.73 m ² were excluded. Propensity score matching was performed for demographics, cardiovascular comorbidities, medication use, body mass index, and hemoglobin A1c. Outcomes were assessed from 1 day after the index date through 5 years and included all-cause mortality, all-cause hospitalization, acute myocardial infarction, cerebrovascular accident, and acute heart failure. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Kaplan-Meier survival analysis. Results: Among 35,753 eligible women with PCOS and T2DM receiving metformin, 5,747 received tirzepatide and 30,006 did not. After propensity score matching, 4,345 women were included in each cohort. Tirzepatide use was associated with lower five-year hazards of all-cause mortality (0.2% vs 1.5%; HR, 0.10; 95% CI, 0.02 - 0.40; p<0.01), all-cause hospitalization (32.8% vs 52.6%; HR, 0.86; 95% CI, 0.80 - 0.92; p<0.01), acute myocardial infarction (1.2% vs 7.5%; HR, 0.21; 95% CI, 0.03 - 0.35; p<0.01), and acute heart failure (4.4% vs 10.9%; HR, 0.69; 95% CI, 0.58 - 0.83; p=0.01). Tirzepatide use was not significantly associated with cerebrovascular accident (1.0% vs 3.0%; HR, 0.74; 95% CI, 0.50 - 1.08; p=0.11). Conclusion: In women with PCOS and T2DM receiving metformin, tirzepatide use was associated with lower five-year hazards of all-cause mortality, all-cause hospitalization, acute myocardial infarction, and acute heart failure. These findings highlight a potential cardiovascular benefit of tirzepatide in women with a high-risk cardiometabolic profile and support further prospective studies to validate these findings.