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PLoS One. 2015 May 20;10(5):e0124287. doi: 10.1371/journal.pone.0124287. eCollection 2015.

Differential cardiovascular outcomes after dipeptidyl peptidase-4 inhibitor, sulfonylurea, and pioglitazone therapy, all in combination with metformin, for type 2 diabetes: a population-based cohort study.

Author information

1
Office of Drug Safety Information II, Korea Institute of Drug Safety & Risk Management, Seoul, Republic of Korea; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
2
Division of Clinical Epidemiology, Medical Research Collaborating Center, Seoul National University College of Medicine/Seoul National University Hospital, Seoul, Republic of Korea; Medical Research Center, Seoul National University, Seoul, Republic of Korea.
3
Office of Drug Utilization Review, Korea Institute of Drug Safety & Risk Management, Seoul, Republic of Korea.
4
Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, Republic of Korea.
5
Office of Drug Safety Information I, Korea Institute of Drug Safety & Risk Management, Seoul, Republic of Korea.
6
Division of Clinical Epidemiology, Medical Research Collaborating Center, Seoul National University College of Medicine/Seoul National University Hospital, Seoul, Republic of Korea.
7
Department of Family Medicine, Seoul National University Bundang Hospital, Seoul, Republic of Korea.
8
Office of Drug Safety Information II, Korea Institute of Drug Safety & Risk Management, Seoul, Republic of Korea; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Office of Drug Utilization Review, Korea Institute of Drug Safety & Risk Management, Seoul, Republic of Korea; Office of Drug Safety Information I, Korea Institute of Drug Safety & Risk Management, Seoul, Republic of Korea.

Abstract

BACKGROUND/OBJECTIVES:

Data on the comparative effectiveness of oral antidiabetics on cardiovascular outcomes in a clinical practice setting are limited. This study sought to determine whether a differential risk of cardiovascular disease (CVD) exists for the combination of a dipeptidyl peptidase-4 (DPP-4) inhibitor plus metformin versus a sulfonylurea derivative plus metformin or pioglitazone plus metformin.

METHODS:

We conducted a cohort study of 349,476 patients who received treatment with a DPP-4 inhibitor, sulfonylurea, or pioglitazone plus metformin for type 2 diabetes using the Korean national health insurance claims database. The incidence of total CVD and individual outcomes of myocardial infarction (MI), heart failure (HF), and ischemic stroke (IS) were assessed using the hazard ratios (HRs) estimated from a Cox proportional-hazards model weighted for a propensity score.

RESULTS:

During follow-up, 3,881 patients developed a CVD, including 428 MIs, 212 HFs, and 1,487 ISs. The adjusted HR with 95% confidence interval (CI) for a sulfonylurea derivative plus metformin compared with a DPP-4 inhibitor plus metformin was 1.20 (1.09-1.32) for total CVD; 1.14 (1.04-1.91) for MI; 1.07 (0.71-1.62) for HF; and 1.51 (1.28-1.79) for IS. The HRs with 95% CI for total CVD, MI, HF, and IS for pioglitazone plus metformin were 0.89 (0.81-0.99), 1.05 (0.76-1.46), 4.81 (3.53-6.56), and 0.81 (0.67-0.99), respectively.

CONCLUSIONS:

Compared with a DPP-4 inhibitor plus metformin, treatment with a sulfonylurea drug plus metformin was associated with increased risks of total CVD, MI, and IS, whereas the use of pioglitazone plus metformin was associated with decreased total CVD and IS risks.

PMID:
25992614
PMCID:
PMC4439115
DOI:
10.1371/journal.pone.0124287
[Indexed for MEDLINE]
Free PMC Article

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