The efficacy and safety of dapagliflozin in women and men with type 2 diabetes mellitus

O'Donoghue, Michelle L, Kato, Eri T, Mosenzon, Ofri, Murphy, Sabina A, Cahn, Avivit, Herrera, Marisol, Tankova, Tsvetalina, Smahelova, Alena, Merlini, Piera, Gause-Nilsson, Ingrid
et al (show 8 more authors) (2021) The efficacy and safety of dapagliflozin in women and men with type 2 diabetes mellitus. DIABETOLOGIA, 64 (6). pp. 1226-1234.

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<h4>Aims/hypothesis</h4>Women remain underrepresented in clinical trials and those with type 2 diabetes mellitus are at high risk for cardiovascular (CV) events. The sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin reduces the risk of CV death or heart failure hospitalisations in individuals with type 2 diabetes. Here, we performed a pre-specified analysis to examine whether sex modifies these effects.<h4>Methods</h4>The DECLARE-TIMI 58 trial randomised 17,160 patients with type 2 diabetes with or at risk for atherosclerotic disease to dapagliflozin or placebo (median follow-up 4.2 years). The dual efficacy outcomes were CV death or heart failure hospitalisations, and major adverse cardiovascular events (MACE; CV death, myocardial infarction or ischaemic stroke). The renal-specific composite outcome was a sustained ≥40% drop in eGFR to <60 ml min<sup>-1</sup> [1.73 m]<sup>-2</sup>, new end-stage renal disease or renal death. Cox models were run separately by sex with treatment-by-sex interaction testing for each outcome.<h4>Results</h4>At baseline, women (n = 6422, 37.4%) had higher HbA<sub>1c</sub>, longer type 2 diabetes duration, and were on fewer glucose-lowering medications. There was no evidence of modification of the effect of dapagliflozin by sex for (1) CV death or heart failure hospitalisations: women (3.8% vs 4.5%; HR 0.84, 95% CI 0.66, 1.07) and men (5.3% vs 6.4%; HR 0.83, 95% CI 0.71, 0.96; p<sub>interaction</sub> = 0.90); (2) MACE: women (6.3% vs 6.8%; HR 0.93, 95% CI 0.77, 1.12) and men (10.0% vs 10.7%; HR 0.93, 95% CI 0.83, 1.05; p<sub>interaction</sub> = 0.99); or (3) renal-specific composite: women (1.4% vs 2.8%; HR 0.50, 95% CI 0.35, 0.70) and men (1.5% vs 2.5%; HR 0.55, 95% CI 0.42, 0.73; p<sub>interaction</sub> = 0.64). The overall safety profile of dapagliflozin was similar for women and men.<h4>Conclusions/interpretation</h4>Dapagliflozin offers comparable CV and renal benefits and a comparable safety profile in women and men.<h4>Funding</h4>AstraZeneca.<h4>Trial registration</h4> NCT01730534.

Item Type: Article
Uncontrolled Keywords: Cardiovascular outcomes, Clinical trials, SGLT2 inhibitors, Women
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 22 Apr 2021 09:11
Last Modified: 18 Jan 2023 22:51
DOI: 10.1007/s00125-021-05399-2
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