Dipeptidyl Peptidase-4 Inhibitors, Peripheral Arterial Disease, and Lower Extremity Amputation Risk in Diabetic Patients

Background Recent studies have elucidated the vascular protective effects of dipeptidyl peptidase-4 (DPP-4) inhibitors. However, to date, no large-scale studies have been carried out to determine the impact of DPP-4 inhibitors on the occurrence of peripheral arterial disease, and lower extremity amputation risk in patients with type 2 diabetes mellitus. Methods We conducted a retrospective registry analysis using Taiwan's National Health Insurance Research Database to investigate the correlation between the use of DPP-4 inhibitors and risk of peripheral arterial disease in patients with type 2 diabetes mellitus. A total of 82,169 propensity score-matched pairs of DPP-4 inhibitor users and nonusers with type 2 diabetes mellitus were examined for the period 2009 to 2011. Results The mean age of the study subjects was 58.9 ± 12.0 years, and 54% of subjects were male. During the mean follow-up of 3.0 years (maximum, 4.8 years), a total of 3369 DPP-4 inhibitor users and 3880 DPP-4 inhibitor nonusers were diagnosed with peripheral arterial disease. Compared with nonusers, DPP-4 inhibitor users were associated with a lower risk of peripheral arterial disease (hazard ratio 0.84; 95% confidence interval, 0.80-0.88). Additionally, DPP-4 inhibitor users had a decreased risk of lower-extremity amputation than nonusers (hazard ratio 0.65; 95% confidence interval, 0.54-0.79). The association between use of DPP-4 inhibitors and risk of peripheral arterial disease was also consistent in subgroup analysis. Conclusions This large-scale nationwide population-based cohort study is the first to demonstrate that treatment with DPP-4 inhibitors is associated with lower risk of peripheral arterial disease occurrence and limb amputation in patients with type 2 diabetes mellitus.