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


OYAMA Kazuma RAZ Itamar CAHN Avivit KUDER Julia MURPHY Sabina BHATT Deepak L. LEITER Lawrence A. MCGUIRE Darren K. WILDING John P. H. PARK Kyong-Soo GOUDEV Assen DIAZ Rafael ŠPINAR Jindřich GAUSE-NILSSON Ingrid A. M. MOSENZON Ofri SABATINE Marc S. WIVIOTT Stephen D.

Year of publication 2022
Type Article in Periodical
Magazine / Source European Heart Journal
MU Faculty or unit

Faculty of Medicine

Web https://academic.oup.com/eurheartj/advance-article-abstract/doi/10.1093/eurheartj/ehab530/6356825?redirectedFrom=fulltext
Doi http://dx.doi.org/10.1093/eurheartj/ehab530
Keywords Type 2 diabetes mellitus • Obesity • Cardiovascular death; Heart failure; Sodium-glucose co transporter 2 inhibitors
Description 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.

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