The Combination of DPP-4 Inhibitors Versus Sulfonylureas with Metformin After Failure of First-line Treatment in the Risk for Major Cardiovascular Events and Death

Apr 5, 2015Canadian journal of diabetes

Risk of major heart problems and death when combining DPP-4 inhibitors versus sulfonylureas with metformin after first treatment stops working

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Abstract

The use of a DPP-4 inhibitor with metformin is associated with a 38% decreased risk for major cardiovascular events and all-cause mortality compared to a sulfonylurea with metformin.

The cohort included 11,807 patients, with 2,286 on the DPP-4 inhibitor-metformin combination and 9,521 on the sulfonylurea-metformin combination.
Crude incidence rates of major adverse cardiovascular events and all-cause mortality were 1.2% per year for the DPP-4 inhibitor group and 2.2% for the sulfonylurea group.
In adjusted analyses, the DPP-4 inhibitor-metformin combination was linked to an adjusted hazard ratio of 0.62 for the composite endpoint.
Findings suggest the DPP-4 inhibitor combination may reduce the risk of myocardial infarction, stroke, and all-cause mortality.

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OBJECTIVE: To determine whether the combination of dipeptidyl-peptidase 4 (DPP-4) inhibitors vs. sulfonylureas with metformin after failure of first-line treatment is associated with a decreased risk for major adverse cardiovascular events (myocardial infarction and stroke) and for all-cause mortality.

METHOD: Using the UK Clinical Practice Research Datalink, a cohort of patients newly treated with metformin or sulfonylurea monotherapy between January 1, 1988, and December 31, 2011, was identified and was followed until December 31, 2012. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models to compare the DPP-4 inhibitor-metformin combination to the sulfonylurea-metformin combination so as to study the risk for a composite endpoint consisting of myocardial infarction, stroke and all-cause mortality. The models were adjusted for high-dimensional propensity score deciles.

RESULTS: The cohort consisted of 11,807 patients that included 2286 on a DPP-4 inhibitor-metformin combination and 9521 on a sulfonylurea-metformin combination. The crude incidence rates (95% CIs) of the composite endpoint were 1.2% (0.8% to 1.7%) and 2.2% (1.9% to 2.5%) per year for the DPP-4 inhibitor-metformin and sulfonylurea-metformin combinations, respectively. In the high-dimensional propensity score-adjusted model, the use of the DPP-4 inhibitor-metformin combination was associated with a 38% decreased risk for the composite endpoint (adjusted HR: 0.62; 95% CI 0.40 to 0.98), compared with the sulfonylurea-metformin combination.

CONCLUSIONS: The use of a DPP-4 inhibitor combination with metformin, compared with a sulfonylurea-metformin combination, was associated with decreased risks for major cardiovascular events and all-cause mortality.

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The Combination of DPP-4 Inhibitors Versus Sulfonylureas with Metformin After Failure of First-line Treatment in the Risk for Major Cardiovascular Events and Death

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