Canagliflozin and Cardiovascular (CV) Outcomes in Patients with Chronic Kidney Disease

SGLT2 inhibitors are approved for glucose lowering in type 2 diabetes (T2DM) and have proven CV benefits, but are not approved for people with significantly reduced kidney function as glycemic efficacy is dependent on glomerular filtration. This analysis of the CANagliflozin cardioVascular Assessment Study (CANVAS) Program assessed effects of canagliflozin on CV outcomes in T2DM according to kidney function (estimated glomerular filtration rate [eGFR] <45, 45-<60, 60-<90, and ≥90 ml/min/1.73 m2). The CANVAS Program included 2039 patients (20.1%) with baseline eGFR <60 ml/min/1.73 m2 (mean age 68 y, BP 138/76 mmHg, HbA1c 8.3%, eGFR 49 ml/min/1.73 m2, median urinary albumin:creatinine ratio 22 mg/g). Effects of canagliflozin on HbA1c and body weight were smaller in patients with eGFR <60 vs. ≥60; ml/min/1.73 m2 (-0.43 vs. -0.64%, P-heterogeneity <0.0001, and -1.16 vs. -1.43 kg, P-heterogeneity = 0.0002), but BP effects were similar (-3.89 vs. -4.11 mmHg, P-heterogeneity = 0.21). Relative effects on the primary and most other CV outcomes were similar across four eGFR subgroups, with possible heterogeneity suggested only for the exploratory outcome of stroke (Figure). Results for almost all safety outcomes were also consistent across eGFR subgroups. Despite smaller glycemic effects in people with reduced eGFR, the cardioprotective benefits of canagliflozin are similar across different levels of kidney function. Disclosure B.L. Neuen: Employee; Self; The George Institute for Global Health. T. Ohkuma: None. B. Neal: Research Support; Self; Australian National Health and Medical Research Council Principal Research Fellowship. Other Relationship; Self; Janssen Scientific Affairs, LLC., Roche Pharma, Servier. Research Support; Self; Merck Schering Plough. Advisory Panel; Self; Abbott, Novartis Pharmaceuticals Corporation, Pfizer Inc. 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. 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. 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. G. Fulcher: Other Relationship; Self; Novo Nordisk Inc., Janssen Scientific Affairs, LLC., Boehringer Ingelheim GmbH, Merck Sharp & Dohme Corp. M. Desai: Employee; Self; Janssen Research&Development. Q. Li: Employee; Self; George Institute for Global Health. H. Deng: Employee; Self; Janssen Research&Development. N. Rosenthal: Employee; Self; Janssen Research & Development. M. Jardine: Other Relationship; Self; Fellowships. Research Support; Self; Gambro, Baxter, CSL Behring, Amgen Inc., Eli Lilly and Company, Merck & Co., Inc.. Advisory Panel; Self; Boehringer Ingelheim GmbH, Baxter, Amgen Inc., Roche Pharma. G. Bakris: Other Relationship; Self; Forest Labs, Takeda, Medtronic (15%), Relypsa (15%). Consultant; Self; Takeda, Abbott, CVRx, Johnson&Johnson, Eli Lilly, Food and Drug Administration. Board Member; Self; National Kidney Foundation, American Society of Hypertension. Other Relationship; Self; Editor-Am J Nephrology, HTN ed. UpToDate, Assoc. Ed.- Diabetes Care, Nephrology Dialysis and Transpl. V. Perkovic: Research Support; Self; Australian National Health and Medical Research Council (Senior Research Fellowship and Program Grant). Other Relationship; Self; AbbVie, Boehringer Ingelheim, GlaxoSmithKline, Janssen, and Pfizer. Advisory Panel; Self; AbbVie, Astellas, AstraZeneca, Bayer, Baxter, Bristol-Myers Squibb, Boehringer Ingelheim, Durect, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Novo Nordisk, Pfizer, Pharmalink, Relyps.