Abstract
BackgroundThe effect of combined insulin and dipeptidyl peptidase-4 inhibitor (DPP4i) therapy on major adverse cardiovascular events (MACEs) in patients with diabetic foot is unclear.MethodsWe 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.ResultsAmong 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).ConclusionsThis 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.
Highlights
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
The proportions of retinopathy, nephropathy, neuropathy, peripheral artery disease (PAD) and use of antithrombotic drugs were higher in the combined therapy group than in the other two groups
The incidence of all complications in the DPP4i-based group was still significantly lower than that in the combined therapy group (HR 0.55, 95% confidence interval (CI) 0.51–0.59 for MACEs; hazard ratio (HR) 0.32, 95% confidence intervals (95% CIs) 0.24–0.42 for nonfatal myocardial infarction (MI); 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; HR 0.35, 95% CI 0.30–0.41 for heart failure for admission)
Summary
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. Kawanami et al reported that incretin-based medications, including a dipeptidyl peptidase-4 (DPP-4) inhibitor and a glucagon-like peptide-1 (GLP-1) receptor agonist, showed anti-inflammatory and antioxidant effects and ameliorated atherosclerosis [14]. These results suggest that diabetic vascular complications are due to hyperglycemia and the pleiotropic action of antidiabetic drugs associated with atherosclerosis and endothelial dysfunction [15]
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