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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:64

Enthalten in:

Diabetologia - 64(2021), 6 vom: 10. Juni, Seite 1226-1234

Sprache:

Englisch

Beteiligte Personen:

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

Links:

Volltext

Themen:

1ULL0QJ8UC
Benzhydryl Compounds
Cardiovascular outcomes
Clinical trials
Dapagliflozin
Glucosides
Journal Article
Research Support, Non-U.S. Gov't
SGLT2 inhibitors
Sodium-Glucose Transporter 2 Inhibitors
Women

Anmerkungen:

Date Completed 22.02.2022

Date Revised 22.02.2022

published: Print-Electronic

ClinicalTrials.gov: NCT01730534

Citation Status MEDLINE

doi:

10.1007/s00125-021-05399-2

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM321702220