Journal Article

Cardiovascular outcomes associated with canagliflozin versus other non-gliflozin antidiabetic drugs: population based cohort study

Glynn, Robert J, Patorno, Elisabetta, Everett, Brendan M, Schneeweiss, Sebastian, Kim, Seoyoung C, Liu, Jun, Goldfine, Allison B

2018

Overview

ABSTRACTObjectiveTo evaluate the cardiovascular safety of canagliflozin, a sodium-glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus, in direct comparisons with DPP-4 inhibitors (DPP-4i), GLP-1 receptor agonists (GLP-1RA), or sulfonylureas, as used in routine practice.DesignPopulation based retrospective cohort study.SettingNationwide sample of patients with type 2 diabetes from a large de-identified US commercial healthcare database (Optum Clinformatics Datamart).ParticipantsThree pairwise 1:1 propensity score matched cohorts of patients with type 2 diabetes 18 years and older who initiated canagliflozin or a comparator non-gliflozin antidiabetic agent (ie, a DPP-4i, a GLP-1RA, or a sulfonylurea) between April 2013 and September 2015.Main outcome measuresThe primary outcomes were heart failure admission to hospital and a composite cardiovascular endpoint (comprised of being admitted to hospital for acute myocardial infarction, ischemic stroke, or hemorrhagic stroke). Hazard ratios and 95% confidence intervals were estimated in each propensity score matched cohort controlling for more than 100 baseline characteristics.ResultsDuring a 30 month period, the hazard ratio for heart failure admission to hospital associated with canagliflozin was 0.70 (95% confidence interval 0.54 to 0.92) versus a DPP-4i (n=17 667 pairs), 0.61 (0.47 to 0.78) versus a GLP-1RA (20 539), and 0.51 (0.38 to 0.67) versus a sulfonylurea (17 354 ). The hazard ratio for the composite cardiovascular endpoint associated with canagliflozin was 0.89 (0.68 to 1.17) versus a DPP-4i, 1.03 (0.79 to 1.35) versus a GLP-1RA, and 0.86 (0.65 to 1.13) versus a sulfonylurea. Results were similar in sensitivity analyses further adjusting for baseline hemoglobin A1c levels and in subgroups of patients with and without prior cardiovascular disease or heart failure.ConclusionsIn this large cohort study, canagliflozin was associated with a lower risk of heart failure admission to hospital and with a similar risk of myocardial infarction or stroke in direct comparisons with three different classes of non-gliflozin diabetes treatment alternatives as used in routine care.

• Publisher: British Medical Journal Publishing Group,BMJ Publishing Group LTD,BMJ Publishing Group Ltd
• Subject: Adult / Aged / Antidiabetics / Canagliflozin - therapeutic use / Cardiovascular Diseases - epidemiology / Cardiovascular Diseases - prevention & control / Cerebral infarction / Cohort analysis / Coronary artery disease / Diabetes / Diabetes mellitus / Diabetes mellitus (non-insulin dependent) / Diabetes Mellitus, Type 2 - drug therapy / Dipeptidyl-Peptidase IV Inhibitors - therapeutic use / Disease / Drugs / Endpoint Determination / Female / Glucagon-Like Peptide-1 Receptor - agonists / Glucose / Health risk assessment / Heart attacks / Heart diseases / Heart failure / Hemoglobin / Hemorrhage / Hospitals / Humans / Hypoglycemic Agents - therapeutic use / Ischemia / Laboratories / Male / Middle Aged / Mortality / Myocardial infarction / Population / Population studies / Population-based studies / Propensity Score / Retrospective Studies / Sensitivity analysis / Sodium / Sodium-glucose cotransporter / Stroke / Sulfonylurea / Sulfonylurea Compounds - therapeutic use / United States - epidemiology