TY - JOUR
T1 - The efficacy and safety of dapagliflozin in women and men with type 2 diabetes mellitus
AU - O’Donoghue, Michelle L.
AU - Kato, Eri T.
AU - Mosenzon, Ofri
AU - Murphy, Sabina A.
AU - Cahn, Avivit
AU - Herrera, Marisol
AU - Tankova, Tsvetalina
AU - Šmahelová, Alena
AU - Merlini, Piera
AU - Gause-Nilsson, Ingrid
AU - Langkilde, Anna Maria
AU - McGuire, Darren K.
AU - Wilding, John P.H.
AU - Leiter, Larry A.
AU - Bhatt, Deepak L.
AU - Raz, Itamar
AU - Sabatine, Marc S.
AU - Wiviott, Stephen D.
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.
PY - 2021/6
Y1 - 2021/6
N2 - 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.]
AB - 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.]
KW - Cardiovascular outcomes
KW - Clinical trials
KW - SGLT2 inhibitors
KW - Women
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U2 - 10.1007/s00125-021-05399-2
DO - 10.1007/s00125-021-05399-2
M3 - Article
C2 - 33611623
AN - SCOPUS:85101131947
SN - 0012-186X
VL - 64
SP - 1226
EP - 1234
JO - Diabetologia
JF - Diabetologia
IS - 6
ER -