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Dipeptidyl Peptidase-4 Inhibitors and Risk of Heart Failure in Patients With Type 2 Diabetes Mellitus: A Population-Based Cohort Study.
Circ Heart Fail. 2017 Sep; 10(9)CH

Abstract

BACKGROUND

The association between dipeptidyl-peptidase IV inhibitors (DPP-4i) and heart failure (HF) remains unclear. In 1 randomized controlled trial and some observational studies, DPP-4i reportedly increased the risk of HF, but 2 other randomized controlled trials and observational studies have shown no such risk. Here, we evaluated the risk of HF and cardiovascular outcomes of DPP-4i compared with sulfonylureas.

METHODS AND RESULTS

A population-based retrospective cohort study was conducted using the Korean Health Insurance Review and Assessment Service database from January 1, 2009, to December 31, 2015. Incident users of sulfonylurea and DPP-4i who were not prescribed the comparator drug in the year before treatment initiation were included. DPP-4i-treated and sulfonylurea-treated patients were matched on propensity score, calculated with >40 variables. The risk of hospitalization for HF was evaluated with a Cox proportional hazards model in 255 691 matched pairs. Analyses were conducted in the total patient population and in both strata divided by the presence of cardiovascular disease during the baseline period. The hazard ratios (HRs) of hospitalization for HF for DPP-4i-treated patients were 0.78 (95% confidence interval [CI], 0.67-0.86) in all of the patients, 0.77 (95% CI, 0.68-0.79) in patients with baseline cardiovascular disease, and 0.71 (95% CI, 0.56-0.90) in patients without baseline cardiovascular disease compared with HRs for sulfonylurea-treated patients. Sitagliptin and linagliptin showed statistically lower risk for hospitalization for HF (HR, 0.76; 95% CI, 0.67-0.86 for sitagliptin-prescribed patients; HR, 0.74; 95% CI, 0.59-0.92 for linagliptin-prescribed patients) than for sulfonylurea. The HRs for hospitalization for myocardial infarction and stroke with the use of a DPP-4i versus sulfonylurea were HR, 0.76 (95% CI, 0.67-0.87) and HR, 0.63 (95% CI, 0.60-0.67), respectively.

CONCLUSIONS

Our findings suggest that DPP-4i use did not increase the risk of HF compared with sulfonylurea. In addition, the risks for cardiovascular outcomes were not elevated in DPP-4i-treated patients compared with sulfonylurea-treated patients.

Authors+Show Affiliations

From the Department of Biomedical Informatics (Y.-G.K., D.Y., S.P., R.W.P.), Department of Endocrinology and Metabolism (S.J.H., D.J.K., K.-W. L., H.J.K.), and Department of Biomedical Sciences (R.W.P.), Ajou University School of Medicine, Suwon, South Korea; and Department of Statistics, Ewha Womans University, Seoul, South Korea (S.P.).From the Department of Biomedical Informatics (Y.-G.K., D.Y., S.P., R.W.P.), Department of Endocrinology and Metabolism (S.J.H., D.J.K., K.-W. L., H.J.K.), and Department of Biomedical Sciences (R.W.P.), Ajou University School of Medicine, Suwon, South Korea; and Department of Statistics, Ewha Womans University, Seoul, South Korea (S.P.).From the Department of Biomedical Informatics (Y.-G.K., D.Y., S.P., R.W.P.), Department of Endocrinology and Metabolism (S.J.H., D.J.K., K.-W. L., H.J.K.), and Department of Biomedical Sciences (R.W.P.), Ajou University School of Medicine, Suwon, South Korea; and Department of Statistics, Ewha Womans University, Seoul, South Korea (S.P.).From the Department of Biomedical Informatics (Y.-G.K., D.Y., S.P., R.W.P.), Department of Endocrinology and Metabolism (S.J.H., D.J.K., K.-W. L., H.J.K.), and Department of Biomedical Sciences (R.W.P.), Ajou University School of Medicine, Suwon, South Korea; and Department of Statistics, Ewha Womans University, Seoul, South Korea (S.P.).From the Department of Biomedical Informatics (Y.-G.K., D.Y., S.P., R.W.P.), Department of Endocrinology and Metabolism (S.J.H., D.J.K., K.-W. L., H.J.K.), and Department of Biomedical Sciences (R.W.P.), Ajou University School of Medicine, Suwon, South Korea; and Department of Statistics, Ewha Womans University, Seoul, South Korea (S.P.).From the Department of Biomedical Informatics (Y.-G.K., D.Y., S.P., R.W.P.), Department of Endocrinology and Metabolism (S.J.H., D.J.K., K.-W. L., H.J.K.), and Department of Biomedical Sciences (R.W.P.), Ajou University School of Medicine, Suwon, South Korea; and Department of Statistics, Ewha Womans University, Seoul, South Korea (S.P.).From the Department of Biomedical Informatics (Y.-G.K., D.Y., S.P., R.W.P.), Department of Endocrinology and Metabolism (S.J.H., D.J.K., K.-W. L., H.J.K.), and Department of Biomedical Sciences (R.W.P.), Ajou University School of Medicine, Suwon, South Korea; and Department of Statistics, Ewha Womans University, Seoul, South Korea (S.P.). veritas@ajou.ac.kr jinkim@ajou.ac.kr.From the Department of Biomedical Informatics (Y.-G.K., D.Y., S.P., R.W.P.), Department of Endocrinology and Metabolism (S.J.H., D.J.K., K.-W. L., H.J.K.), and Department of Biomedical Sciences (R.W.P.), Ajou University School of Medicine, Suwon, South Korea; and Department of Statistics, Ewha Womans University, Seoul, South Korea (S.P.). veritas@ajou.ac.kr jinkim@ajou.ac.kr.

Pub Type(s)

Comparative Study
Journal Article
Observational Study

Language

eng

PubMed ID

28899989

Citation

Kim, Young-Gun, et al. "Dipeptidyl Peptidase-4 Inhibitors and Risk of Heart Failure in Patients With Type 2 Diabetes Mellitus: a Population-Based Cohort Study." Circulation. Heart Failure, vol. 10, no. 9, 2017.
Kim YG, Yoon D, Park S, et al. Dipeptidyl Peptidase-4 Inhibitors and Risk of Heart Failure in Patients With Type 2 Diabetes Mellitus: A Population-Based Cohort Study. Circ Heart Fail. 2017;10(9).
Kim, Y. G., Yoon, D., Park, S., Han, S. J., Kim, D. J., Lee, K. W., Park, R. W., & Kim, H. J. (2017). Dipeptidyl Peptidase-4 Inhibitors and Risk of Heart Failure in Patients With Type 2 Diabetes Mellitus: A Population-Based Cohort Study. Circulation. Heart Failure, 10(9). https://doi.org/10.1161/CIRCHEARTFAILURE.117.003957
Kim YG, et al. Dipeptidyl Peptidase-4 Inhibitors and Risk of Heart Failure in Patients With Type 2 Diabetes Mellitus: a Population-Based Cohort Study. Circ Heart Fail. 2017;10(9) PubMed PMID: 28899989.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dipeptidyl Peptidase-4 Inhibitors and Risk of Heart Failure in Patients With Type 2 Diabetes Mellitus: A Population-Based Cohort Study. AU - Kim,Young-Gun, AU - Yoon,Dukyong, AU - Park,Sooyoung, AU - Han,Seung Jin, AU - Kim,Dae Jung, AU - Lee,Kwan-Woo, AU - Park,Rae Woong, AU - Kim,Hae Jin, PY - 2017/02/13/received PY - 2017/08/15/accepted PY - 2017/9/14/entrez PY - 2017/9/14/pubmed PY - 2017/9/26/medline KW - cardiovascular diseases KW - dipeptidyl-peptidase IV inhibitors KW - heart failure KW - myocardial infarction JF - Circulation. Heart failure JO - Circ Heart Fail VL - 10 IS - 9 N2 - BACKGROUND: The association between dipeptidyl-peptidase IV inhibitors (DPP-4i) and heart failure (HF) remains unclear. In 1 randomized controlled trial and some observational studies, DPP-4i reportedly increased the risk of HF, but 2 other randomized controlled trials and observational studies have shown no such risk. Here, we evaluated the risk of HF and cardiovascular outcomes of DPP-4i compared with sulfonylureas. METHODS AND RESULTS: A population-based retrospective cohort study was conducted using the Korean Health Insurance Review and Assessment Service database from January 1, 2009, to December 31, 2015. Incident users of sulfonylurea and DPP-4i who were not prescribed the comparator drug in the year before treatment initiation were included. DPP-4i-treated and sulfonylurea-treated patients were matched on propensity score, calculated with >40 variables. The risk of hospitalization for HF was evaluated with a Cox proportional hazards model in 255 691 matched pairs. Analyses were conducted in the total patient population and in both strata divided by the presence of cardiovascular disease during the baseline period. The hazard ratios (HRs) of hospitalization for HF for DPP-4i-treated patients were 0.78 (95% confidence interval [CI], 0.67-0.86) in all of the patients, 0.77 (95% CI, 0.68-0.79) in patients with baseline cardiovascular disease, and 0.71 (95% CI, 0.56-0.90) in patients without baseline cardiovascular disease compared with HRs for sulfonylurea-treated patients. Sitagliptin and linagliptin showed statistically lower risk for hospitalization for HF (HR, 0.76; 95% CI, 0.67-0.86 for sitagliptin-prescribed patients; HR, 0.74; 95% CI, 0.59-0.92 for linagliptin-prescribed patients) than for sulfonylurea. The HRs for hospitalization for myocardial infarction and stroke with the use of a DPP-4i versus sulfonylurea were HR, 0.76 (95% CI, 0.67-0.87) and HR, 0.63 (95% CI, 0.60-0.67), respectively. CONCLUSIONS: Our findings suggest that DPP-4i use did not increase the risk of HF compared with sulfonylurea. In addition, the risks for cardiovascular outcomes were not elevated in DPP-4i-treated patients compared with sulfonylurea-treated patients. SN - 1941-3297 UR - https://www.unboundmedicine.com/medline/citation/28899989/Dipeptidyl_Peptidase_4_Inhibitors_and_Risk_of_Heart_Failure_in_Patients_With_Type_2_Diabetes_Mellitus:_A_Population_Based_Cohort_Study_ L2 - https://www.ahajournals.org/doi/10.1161/CIRCHEARTFAILURE.117.003957?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -