Relatively Consistent Effects of Canagliflozin (CANA) on Outcomes Regardless of Baseline HbA1c in the CANagliflozin CardioVascular Assessment Study (CANVAS) Program
Authors: ROSENSTOCK JULIO , BANTWAL GANAPATHI , WILDING JOHN P. , DUMAS RICHARD , GONZALEZ-GALVEZ GUILLERMO , SLEE APRIL , VERCRUYSSE FRANK , MAHAFFEY KENNETH W. , ZEEUW DICK DE , FULCHER GREGORY , MATTHEWS DAVID R. 
Published: June 2018

A prespecified analysis of the CANVAS Program assessed the effects of CANA, an SGLT2 inhibitor, on the risk of cardiovascular (CV), mortality, and renal outcomes in participants with type 2 diabetes mellitus (T2DM) and established CV disease (CVD) or with ≥2 CV risk factors by baseline HbA1c. The primary composite outcome of CV death, nonfatal myocardial infarction, or nonfatal stroke was significantly reduced with CANA vs. placebo (PBO) in the total cohort by 14% (HR 0.86; 95% CI, 0.75, 0.97; P = 0.02). Among CANVAS Program participants, 4,411 (43%) had baseline HbA1c &lt;8% (mean HbA1c 7.4%; prior CVD 67%; age 64 y; BMI 32 kg/m2; and BP 136/77 mmHg) and 5,731 (57%) had baseline HbA1c ≥8% (mean HbA1c 8.9%; prior CVD 65%; age 63 y; BMI 32 kg/m2; and BP 137/78 mmHg). The effects of CANA on CV and renal outcomes were similar overall in participants with baseline HbA1c &lt;8% or ≥8%, but there was evidence of statistical heterogeneity between subgroups for CV death and all-cause mortality, where effects on these adverse outcomes were better in participants with HbA1c ≥8% (Figure).
In summary, CV and renal outcomes appeared better in CANA-treated participants regardless of HbA1c in this hypothesis-generating subanalysis with a suggestion of greater effects on lowering mortality risk in those with higher HbA1c levels at baseline.

Disclosure
J. Rosenstock: Advisory Panel; Self; Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Advisory Panel; Self; Sanofi. Consultant; Self; Sanofi. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Intarcia Therapeutics, Inc.. Consultant; Self; Intarcia Therapeutics, Inc.. Research Support; Self; Merck & Co., Inc., Pfizer Inc., Sanofi, Novo Nordisk Inc., Bristol-Myers Squibb Company, Eli Lilly and Company, Intarcia Therapeutics, Inc., Genentech, Inc. G. Bantwal: Speaker's Bureau; Self; Abbott. Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; Biocon, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi-Aventis. J.P. Wilding: Other Relationship; Self; Astellas, AstraZeneca, Boehringer Ingelheim GmbH, Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi, Eli Lilly and Company, Orexigen Therapeutics, Inc., Merck & Co., Inc. R. Dumas: Speaker's Bureau; Self; Janssen Ortho, Merck, Novo Nordisk, Lilly, Aventis, Boehringer Ingelheim Astra Zeneca, BMS. Consultant; Self; Janssen Ortho, Merck, Novo Nordisk, Lilly, Aventis, Boehringer Ingelheim Astra Zeneca, BMS. Research Support; Self; Janssen Ortho, Merck, Novo Nordisk, Lilly, Aventis, Boehringer Ingelheim Astra Zeneca, BMS. G. Gonzalez-Galvez: None. A. Slee: Other Relationship; Self; Janssen Scientific Affairs, LLC. F. Vercruysse: 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. G. Fulcher: Other Relationship; Self; Novo Nordisk Inc., Janssen Scientific Affairs, LLC., Boehringer Ingelheim GmbH, Merck Sharp & Dohme Corp. 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.