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

Feb 14, 2018BMJ (Clinical research ed.)

Heart health outcomes linked to canagliflozin compared to other diabetes drugs in a large patient group

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Abstract

The hazard ratio for heart failure admission to hospital associated with canagliflozin was 0.70 compared to DPP-4 inhibitors.

Canagliflozin may lower the risk of heart failure admissions compared to DPP-4 inhibitors, GLP-1 receptor agonists, and sulfonylureas.
The hazard ratios for heart failure admissions were 0.70 versus DPP-4i, 0.61 versus GLP-1RA, and 0.51 versus sulfonylurea.
Canagliflozin was associated with a similar risk for a composite cardiovascular endpoint compared to these treatment options.
The hazard ratio for the composite cardiovascular endpoint was 0.89 versus DPP-4i, 1.03 versus GLP-1RA, and 0.86 versus sulfonylurea.
Results were consistent across various patient subgroups and after adjusting for baseline hemoglobin A1c levels.

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OBJECTIVE: To 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.

DESIGN: Population based retrospective cohort study.

SETTING: Nationwide sample of patients with type 2 diabetes from a large de-identified US commercial healthcare database (Optum Clinformatics Datamart).

PARTICIPANTS: Three 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 MEASURES: The 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.

RESULTS: During 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.

CONCLUSIONS: In 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.

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

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