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

Michelle L. O’Donoghue, Eri T. Kato, Ofri Mosenzon, Sabina A. Murphy, Avivit Cahn, Marisol Herrera, Tsvetalina Tankova, Alena Šmahelová, Piera Merlini, Ingrid Gause-Nilsson, Anna Maria Langkilde, Darren K. McGuire, John P.H. Wilding, Larry A. Leiter, Deepak L. Bhatt, Itamar Raz, Marc S. Sabatine, Stephen D. Wiviott

Research output: Contribution to journalArticlepeer-review

Abstract

Aims/hypothesis: 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. Methods: 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−1 [1.73 m]−2, new end-stage renal disease or renal death. Cox models were run separately by sex with treatment-by-sex interaction testing for each outcome. Results: At baseline, women (n = 6422, 37.4%) had higher HbA1c, 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; pinteraction = 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; pinteraction = 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; pinteraction = 0.64). The overall safety profile of dapagliflozin was similar for women and men. Conclusions/interpretation: Dapagliflozin offers comparable CV and renal benefits and a comparable safety profile in women and men. Funding: AstraZeneca. Trial registration: clinicaltrials.gov NCT01730534. Graphical abstract: [Figure not available: see fulltext.]

Original languageEnglish (US)
Pages (from-to)1226-1234
Number of pages9
JournalDiabetologia
Volume64
Issue number6
DOIs
StatePublished - Jun 2021

Keywords

  • Cardiovascular outcomes
  • Clinical trials
  • SGLT2 inhibitors
  • Women

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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