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

Abstract

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.

• Authors: Shuo-Ming Ou, Chia-Jen Shih, Pei-Wen Chao, Hsi Chu, Shu-Chen Kuo, Yi-Jung Lee, Shuu-Jiun Wang, Chih-Yu Yang, Chih-Ching Lin, Tzeng-Ji Chen, Der-Cherng Tarng, Szu-Yuan Li, Yung-Tai Chen
• Journal: Annals of internal medicine (Ann Intern Med) Vol. 163 Issue 9 Pg. 663-72 (Nov 03 2015) ISSN: 1539-3704 [Electronic] United States
• PMID: 26457538 (Publication Type: Journal Article, Observational Study)

Chemical References

• Dipeptidyl-Peptidase IV Inhibitors
• Hypoglycemic Agents
• Sulfonylurea Compounds
• Metformin

Topics

• Cardiovascular Diseases (etiology)
• Cause of Death
• Diabetes Mellitus, Type 2 (complications, drug therapy)
• Dipeptidyl-Peptidase IV Inhibitors (adverse effects, therapeutic use)
• Drug Therapy, Combination
• Female
• Heart Failure (etiology)
• Humans
• Hypoglycemia (chemically induced)
• Hypoglycemic Agents (adverse effects, therapeutic use)
• Male
• Metformin (therapeutic use)
• Middle Aged
• Myocardial Infarction (etiology)
• Propensity Score
• Stroke (etiology)
• Sulfonylurea Compounds (adverse effects, therapeutic use)
• Treatment Outcome