Obesity and effects of dapagliflozin on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus in the DECLARE-TIMI 58 trial

Eur Heart J. 2022 Aug 14;43(31):2958-2967. doi: 10.1093/eurheartj/ehab530.


Aims: We investigated the associations between obesity, cardiorenal events, and benefits of dapagliflozin in patients with type 2 diabetes mellitus (T2DM).

Methods and results: DECLARE-TIMI 58 randomized patients with T2DM and either atherosclerotic cardiovascular (CV) disease or multiple risk factors to dapagliflozin vs. placebo. Patients were stratified by body mass index (BMI, kg/m2): normal (18.5 to <25), overweight (25 to <30), moderately obese (30 to <35), severely obese (35 to <40), and very-severely obese (≥40). Outcomes analysed were CV death, hospitalization for heart failure (HHF), renal-specific composite outcome, and atrial fibrillation or flutter (AF/AFL). Of 17 134 patients, 9.0% had a normal BMI, 31.5% were overweight, 32.4% were moderately, 17.2% severely, and 9.8% were very-severely obese. Higher BMI was associated with a higher adjusted risk of HHF and AF/AFL (hazard ratio 1.30 and 1.28, respectively, per 5 kg/m2; P < 0.001 for all). Dapagliflozin reduced body weight by similar relative amounts consistently across BMI categories (percent difference: -1.9 to -2.4%). Although relative risk reductions in CV and renal-specific composite outcomes with dapagliflozin did not significantly differ across the range of BMI (P for interaction ≥0.20 for all outcomes), obese patients (BMI ≥ 30 kg/m2) tended to derive greater absolute risk reduction in HHF and AF/AFL (P for interaction 0.02 and 0.09, respectively) than non-obese patients.

Conclusions: In DECLARE-TIMI 58, patients with T2DM and higher BMI were more likely to have HHF and AF/AFL. Whereas relative risk reductions in CV and renal outcomes with dapagliflozin were generally consistent across the range of BMI, absolute risk reduction in obesity-related outcomes including HHF and AF/AFL tended to be larger in obese patients with T2DM.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01730534.

Keywords: Cardiovascular death; Heart failure; Obesity; Sodium-glucose co transporter 2 inhibitors; Type 2 diabetes mellitus.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Benzhydryl Compounds
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Glucosides
  • Heart Failure* / drug therapy
  • Humans
  • Obesity / complications
  • Overweight
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use


  • Benzhydryl Compounds
  • Glucosides
  • Sodium-Glucose Transporter 2 Inhibitors
  • dapagliflozin

Associated data

  • ClinicalTrials.gov/NCT01730534