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, Itamar RAZ, Avivit CAHN, Julia KUDER, Sabina MURPHY, Deepak L. BHATT, Lawrence A. LEITER, Darren K. MCGUIRE, John P. H. WILDING, Kyong-Soo PARK, Assen GOUDEV, Rafael DIAZ, Jindřich ŠPINAR, Ingrid A. M. GAUSE-NILSSON, Ofri MOSENZON, Marc S. SABATINE and Stephen D. WIVIOTT. Obesity and effects of dapagliflozin on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus in the DECLARE–TIMI 58 trial. European Heart Journal. OXFORD: OXFORD UNIV PRESS, 2022, vol. 43, No 31, p. 2958-2967. ISSN 0195-668X. Available from: https://dx.doi.org/10.1093/eurheartj/ehab530.

Basic information

• Original name: Obesity and effects of dapagliflozin on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus in the DECLARE–TIMI 58 trial
• Authors: OYAMA, Kazuma, Itamar RAZ, Avivit CAHN, Julia KUDER, Sabina MURPHY, Deepak L. BHATT, Lawrence A. LEITER, Darren K. MCGUIRE, John P. H. WILDING, Kyong-Soo PARK, Assen GOUDEV, Rafael DIAZ, Jindřich ŠPINAR (203 Czech Republic, belonging to the institution), Ingrid A. M. GAUSE-NILSSON, Ofri MOSENZON, Marc S. SABATINE and Stephen D. WIVIOTT.
• Edition: European Heart Journal, OXFORD, OXFORD UNIV PRESS, 2022, 0195-668X.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 30201 Cardiac and Cardiovascular systems
• Country of publisher: United Kingdom of Great Britain and Northern Ireland
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 39.300
• RIV identification code: RIV/00216224:14110/22:00125194
• Organization unit: Faculty of Medicine
• Doi: http://dx.doi.org/10.1093/eurheartj/ehab530
• UT WoS: 000756673900001
• Keywords in English: Type 2 diabetes mellitus • Obesity • Cardiovascular death; Heart failure; Sodium-glucose co transporter 2 inhibitors
• Tags: 14110115, rivok
• Tags: International impact, Reviewed

Abstract

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.