Coadministration of DPP-4 inhibitor and insulin therapy does not further reduce the risk of cardiovascular events compared with DPP-4 inhibitor therapy in diabetic foot patients: a nationwide population-based study

Yi-Hsuan Lin; Yu-Yao Huang; Yi-Ling Wu; Cheng-Wei Lin; Pei-Chun Chen; Chee Jen Chang; Sheng-Hwu Hsieh; Jui-Hung Sun; Szu-Tah Chen; Chia-Hung Lin

doi:10.1186/s13098-018-0378-6

Coadministration of DPP-4 inhibitor and insulin therapy does not further reduce the risk of cardiovascular events compared with DPP-4 inhibitor therapy in diabetic foot patients: a nationwide population-based study

Diabetol Metab Syndr. 2018 Oct 17:10:75. doi: 10.1186/s13098-018-0378-6. eCollection 2018.

Authors

Yi-Hsuan Lin¹, Yu-Yao Huang^{1

2}, Yi-Ling Wu³, Cheng-Wei Lin¹, Pei-Chun Chen⁴, Chee Jen Chang^{3

5

6

7}, Sheng-Hwu Hsieh¹, Jui-Hung Sun¹, Szu-Tah Chen¹, Chia-Hung Lin^{1

5

8}

Affiliations

¹ Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, 5, Fusing St, Gueishan Township, Taoyuan County, 333 Taiwan.
² Department of Medical Nutrition Therapy, Chang Gung Memorial Hospital, Linkou, Taiwan.
³ 3Research Services Center for Health Information, Chang Gung University, Taoyuan, Taiwan.
⁴ 4Department of Public Health, China Medical University, Taichung, Taiwan.
⁵ 5Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan.
⁶ 6Clinical Informatics and Medical Statistics Research Center, Chang Gung University, Taoyuan, Taiwan.
⁷ Department of Cardiology, Chang Gung Memorial Hospital, Linkou, Taiwan.
⁸ 8Department of Chinese Medicine, Chang Gung University, Taoyuan, Taiwan.

Abstract

Background: The effect of combined insulin and dipeptidyl peptidase-4 inhibitor (DPP4i) therapy on major adverse cardiovascular events (MACEs) in patients with diabetic foot is unclear.

Methods: We conducted this nationwide cohort study using longitudinal claims data obtained from the Taiwan National Health Insurance program and included 19,791 patients with diabetic foot from 2007 to 2014. Patients receiving DPP4i-based therapy and/or insulin-based therapy after a diagnosis of diabetic foot were categorized into combined, DPP4i- or insulin-based groups, respectively. The risk of MACEs including nonfatal myocardial infarction, nonfatal stroke, cardiac death, and heart failure was assessed using Cox proportional hazards analysis and propensity score matching.

Results: Among the 19,791 patients with diabetic foot (mean age, 58.8 years [SD, 12.5]; men, 51.2%), 6466 received DPP4i-based therapy, 1925 received insulin-based therapy, and 11,400 received combined DPP4i and insulin therapy. The DPP4i-based and insulin-based groups had a lower risk of MACEs (HR 0.53, 95% CI 0.50-0.57 DPP4i only; HR 0.89, 95% CI 0.81-0.97 insulin only) than the combined group. After propensity score matching, the incidence of all complications in the DPP4i-based group was still significantly lower than that in the combined group (HR 0.55, 95% CI 0.51-0.59 for MACEs; HR 0.32, 95% CI 0.24-0.42 for nonfatal myocardial infarction; HR 0.70, 95% CI 0.63-0.78 for nonfatal stroke; HR 0.22, 95% CI 0.13-0.38 for cardiac death; HR 0.22, 95% CI 0.19-0.25 for any death; HR 0.16, 95% CI 0.13-0.20 for amputation). In the diabetic foot patients with end-stage renal disease (ESRD), the benefit of a lower incidence of MACEs in the DPP4i-based group disappeared (HR 0.77, 95% CI 0.58-1.08).

Conclusions: This study demonstrated that the patients with diabetic foot receiving DPP4i-based therapy had a lower risk of MACEs than those receiving combined therapy with DPP4i and insulin, but that the effect disappeared in those with concurrent ESRD.

Keywords: Cardiovascular complications; Diabetic foot; Dipeptidyl peptidase-4 inhibitor-based therapy; Insulin therapy.