Effects on Clinical Outcomes of Adding Dipeptidyl Peptidase-4 Inhibitors Versus Sulfonylureas to Metformin Therapy in Patients With Type 2 Diabetes Mellitus

Oct 13, 2015Annals of internal medicine

How Adding DPP-4 Inhibitors or Sulfonylureas to Metformin Affects Health in People with Type 2 Diabetes

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Abstract

DPP-4 inhibitors were associated with a 63% lower risk of all-cause death compared to sulfonylureas in patients with type 2 diabetes mellitus.

DPP-4 inhibitors showed a reduced risk for major adverse cardiovascular events, with a hazard ratio of 0.68.
The use of DPP-4 inhibitors was linked to a 64% lower risk of ischemic stroke.
Patients using DPP-4 inhibitors experienced a 57% reduction in hypoglycemia risk.
No significant differences were found in the risk of myocardial infarction or hospitalization for heart failure between the two treatment groups.
The study was an observational analysis using a large cohort from Taiwan's National Health Insurance Research Database.

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BACKGROUND: Recent studies concluded that dipeptidyl peptidase-4 (DPP-4) inhibitors provide glycemic control but also raised concerns about the risk for heart failure in patients with type 2 diabetes mellitus (T2DM). However, large-scale studies of the effects on cardiovascular outcomes of adding DPP-4 inhibitors versus sulfonylureas to metformin therapy remain scarce.

OBJECTIVE: To compare clinical outcomes of adding DPP-4 inhibitors versus sulfonylureas to metformin therapy in patients with T2DM.

DESIGN: Nationwide study using Taiwan's National Health Insurance Research Database.

SETTING: Taiwan.

PATIENTS: All patients with T2DM aged 20 years or older between 2009 and 2012. A total of 10,089 propensity score-matched pairs of DPP-4 inhibitor users and sulfonylurea users were examined.

MEASUREMENTS: Cox models with exposure to sulfonylureas and DPP-4 inhibitors included as time-varying covariates were used to compare outcomes. The following outcomes were considered: all-cause mortality, major adverse cardiovascular events (MACEs) (including ischemic stroke and myocardial infarction), hospitalization for heart failure, and hypoglycemia. Patients were followed until death or 31 December 2013.

RESULTS: DPP-4 inhibitors were associated with lower risks for all-cause death (hazard ratio [HR], 0.63 [95% CI, 0.55 to 0.72]), MACEs (HR, 0.68 [CI, 0.55 to 0.83]), ischemic stroke (HR, 0.64 [CI, 0.51 to 0.81]), and hypoglycemia (HR, 0.43 [CI, 0.33 to 0.56]) compared with sulfonylureas as add-on therapy to metformin but had no effect on risks for myocardial infarction and hospitalization for heart failure.

LIMITATION: Observational study design.

CONCLUSION: Compared with sulfonylureas, DPP-4 inhibitors were associated with lower risks for all-cause death, MACEs, ischemic stroke, and hypoglycemia when used as add-ons to metformin therapy.

PRIMARY FUNDING SOURCE: None.

Effects on Clinical Outcomes of Adding Dipeptidyl Peptidase-4 Inhibitors Versus Sulfonylureas to Metformin Therapy in Patients With Type 2 Diabetes Mellitus

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