What question did this study set out to answer?

This research aims to compare relative and absolute risk reductions for major adverse cardiovascular events (MACE) between sexes in type 2 diabetes patients treated with GLP-1 receptor agonists.

June 7, 2026

1410-P: Relative and Absolute Risk Reduction for MACE in Cardiovascular Outcomes Trials with GLP-1 Receptor Agonists in Female vs. Male People with Type 2 Diabetes

Key Points

This research aims to compare relative and absolute risk reductions for major adverse cardiovascular events (MACE) between sexes in type 2 diabetes patients treated with GLP-1 receptor agonists.
Analyzed cardiovascular outcomes trials (CVOTs) reporting gender-specific results for MACE (N=63,662 total participants).
Calculated percentages of females and males experiencing MACE in placebo and active treatment groups to determine absolute risk reduction.
Pooled results for both sexes over a normalized 3-year observation period.
Relative risk reductions were 0.82 (females, 95% CI: 0.75-0.89) and 0.86 (males, 95% CI: 0.81-0.91), showing no significant difference.
Absolute risk reductions were 1.66% (females, 95% CI 1.45-1.87) and 1.60% (males, 95% CI 1.46-1.73), indicating similar outcomes.
Numbers-needed-to-treat for MACE reduction were 60 for females and 63 for males, also not significantly different.

Abstract

Introduction and Objective: Cardiovascular outcomes trials (CVOTs) with GLP-1 receptor agonists (GLP-1RAs) have recruited people with T2D of both sexes. Meta-analyses suggest a non-significant different hazard ratio comparing active vs. placebo treatment for major adverse cardiovascular events (MACE) considering sex. Absolute risk reductions have not been compared. Methods: CVOTs reporting gender-specific results for MACE were analysed (LEADER, SUSTAIN-6, EXSCEL, HARMONY Outcomes, REWIND, PIONEER-6, AMPLITUDE-O, SOUL). The percentage of female and male participants experiencing MACE events was calculated for placebo and active treatment, and the difference represented absolute risk reduction. For all CVOTs, results were pooled for female and male participants, respectively, and compared. All data were normalized to a 3-year period of observation assuming linear accrual of MACE endpoints. Results: 22,859 patients (or 35.9 %) were female, and 40,803 patients were male. Relative risk reductions (odds ratios) were not significantly different between both subpopulations pooled (female: 0.82 95 % CI: 0.75-0.89; male: 0.86 95 % CI: 0.81-0.91). Absolute risk reductions were similar as well: Female: 1.66 (95 % CI 1.45-1.87) %, male: 1.60 (95 % CI 1.46-1.73) %. Consecutively, the numbers-needed-to-treat for MACE reduction also were not significantly different (female: 60 95 % CI 54-69; male: 63 95 % CI 58-68). The risk for MACE with placebo treatment was higher in male (4.3 95 % CI 4.2-4.5 per 100 PYO) than in female patients (3.3 95 % CI 3.1-3.5 per 100 PYO). Conclusion: Our results confirm that relative risk reduction is not significantly different between female and male patients. In addition, the absolute risk reductions were similar as well, as were the numbers-needed-to-treat, when comparing results in female and male participants. Disclosure Y. Lee-Barkey: Speaker's Bureau; Current; AstraZeneca. Research Support; Current; AstraZeneca, Amgen Inc. Speaker's Bureau; Current; Amgen Inc. Research Support; Ended; Applied Therapeutics. Speaker's Bureau; Ended; Boehringer Ingelheim International GmbH. Research Support; Current; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novartis AG, Novo Nordisk. Advisory Panel; Current; Sanofi. B. Stratmann: Research Support; Current; Amgen Inc. Research Support; Ended; Applied Therapeutics. Research Support; Current; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Novartis AG, Novo Nordisk, Vertex Pharmaceuticals Incorporated, Eli Lilly and Company, Roche Diabetes Care. S. Reger-Tan: Advisory Panel; Current; Abbott Diabetes. Consultant; Current; Abbott Diabetes. Advisory Panel; Current; Bayer AG. Other - Lectures; Current; Boehringer Ingelheim International GmbH. Research Support; Current; Boehringer Ingelheim International GmbH. Advisory Panel; Current; Dexcom, Inc. Research Support; Current; Eli Lilly and Company. Other - Lectures; Current; Eli Lilly and Company. Advisory Panel; Current; Novo Nordisk. Research Support; Current; Novo Nordisk. Other - Lectures; Current; Novo Nordisk. Advisory Panel; Current; Insulet Corporation. Research Support; Current; AstraZeneca, Amgen Inc., Vertex Pharmaceuticals Incorporated. Other - Lectures; Current; Abbott Diabetes. Research Support; Current; Novartis AG, Bayer AG, Roche Diabetes Care. Other - Lectures; Ended; Bayer AG, Berlin-Chemie AG, Sanofi-Aventis Deutschland GmbH. Consultant; Current; Medtronic. Research Support; Current; Applied Therapeutics. M.A. Nauck: Advisory Panel; Current; Boehringer Ingelheim International GmbH, Eli Lilly and Company. Speaker's Bureau; Current; Novo Nordisk. Advisory Panel; Current; Pfizer Inc., Regor. Consultant; Current; Structure Therapy. Speaker's Bureau; Current; Eli Lilly and Company, Novo Nordisk, Medscape, Medical Learning Institute. Advisory Panel; Current; Sun Pharmaceutical Industries Ltd.

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