Improved Cardiovascular and Renal Outcomes in the CANagliflozin CardioVascular Assessment Study (CANVAS) Program Irrespective of Baseline (BL) Body Mass Index (BMI)

Abstract

Overweight and obesity increases the risk of heart and kidney disease. The effects of canagliflozin (CANA) in patients with BL BMI <30 or ≥30 kg/m2 was a prespecified analysis in the CANVAS Program. CANA reduced CV and renal outcomes in patients with T2D and high CV risk (N = 10,142). At BL compared to patients with BMI <30 kg/m2, more patients with BMI ≥30 kg/m2 had SBP ≥140 or DBP ≥90 mmHg (47.9% vs. 40.3%) and were taking RAAS inhibitors (83.8% vs. 74.6%). Effects of CANA on the primary outcome (CV death, nonfatal myocardial infarction, or nonfatal stroke) and other CV outcomes were consistent between BMI subgroups (Fig). CANA decreased progression of albuminuria in both BMI subgroups with the effect appearing greater in patients with BMI ≥30 kg/m2. Further statistical testing did not show a qualitative interaction (Gail-Simons P = 0.875). The comparative benefits of CANA on albuminuria in patients with higher BMI may be due to greater reductions in body weight (placebo-subtracted difference at 1 y: -2.1 and -2.8 kg for BMI <30 and ≥30 kg/m2) and BP (SBP: -4.2 and -4.6 mmHg; DBP: -1.0 and -1.7 mmHg for BMI <30 and ≥30 kg/m2); HbA1c reductions were similar with BMI <30 and ≥30 kg/m2 (-0.60% and -0.63%). While small statistical heterogeneity may exist, BMI <30 vs. ≥30 kg/m2 does not appear to be a major determinant of the observed improvements in CV outcomes with CANA. Disclosure H. Bays: Research Support; Self; Amgen Inc. L. Van Gaal: Advisory Panel; Self; Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen J & J, Merck MSD, Novo Nordisk, Sanofi and Servier/Intarcia. Speaker's Bureau; Self; Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen J & J, Merck MSD, Novo Nordisk, Sanofi and Servier/Intarcia. Research Support; Self; EU (Hepadip & Resolve consortium) and National Research Funds. S. Aravind: None. N. Aggarwal: None. R. Violante: Advisory Panel; Self; Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, AstraZeneca, Sanofi-Aventis. Research Support; Self; Novo Nordisk Inc., Merck Sharp & Dohme Corp., Eli Lilly and Company, Janssen Pharmaceuticals, Inc. A. Slee: Other Relationship; Self; Janssen Scientific Affairs, LLC. W. Shaw: Employee; Self; Janssen Research & Development. K.W. Mahaffey: Research Support; Self; Afferent, Amgen, AstraZeneca, Daiichi, Ferring, Google (Verily), Janssen, Medtronic, Merck, Novartis, Sanofi, and St. Jude. Consultant; Self; Ablynx, AstraZeneca, BAROnova, Bio2 Medical, Boehringer Ingelheim, Bristol-Myers Squibb, Cardiometabolic Health Congress, Cubist, Eli Lilly, Elsevier, Epson, GlaxoSmithKline, Janssen, Merck, Mt. Sinai, Radiometer, Springer Publishing, The Medicines Company, Theravance, Vindico, and WebMD. Stock/Shareholder; Self; BioPrint Fitness. D. de Zeeuw: Other Relationship; Self; AbbVie Inc., Astellas Pharma US, Inc., Eli Lilly and Company, Fresenius SE & Co. KGaA, Janssen Scientific Affairs, LLC., Boehringer Ingelheim GmbH, Bayer AG, Mitsubishi Tanabe Pharma Corporation. D.R. Matthews: Other Relationship; Self; Janssen Scientific Affairs, LLC., Novo Nordisk Inc., GlaxoSmithKline plc., Novartis Pharmaceuticals Corporation, Eli Lilly and Company, Sanofi-Aventis, Servier, Aché Laboratories.