title: Dipeptidyl Peptidase-4 Inhibitors, Peripheral Arterial Disease, and Lower Extremity Amputation Risk in Diabetic Patients.
abstract: 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.
authors.affiliation: Division of Cardiology, Taipei Veterans General Hospital Taoyuan Branch, Taiwan; Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chun-Chin
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Medicine, Taipei City Hospital, Heping Fuyou Branch, Taiwan.
authors.forename: Yung-Tai
authors.initials: YT
authors.lastname: Chen
authors.affiliation: Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Taipei Medical University, Taiwan.
authors.forename: Chien-Yi
authors.initials: CY
authors.lastname: Hsu
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taiwan.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Su
authors.affiliation: Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taiwan.
authors.forename: Chun-Chih
authors.initials: CC
authors.lastname: Chiu
authors.affiliation: Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taiwan; Healthcare and Management Center, Taipei Veterans General Hospital, Taiwan.
authors.forename: Hsin-Bang
authors.initials: HB
authors.lastname: Leu
authors.affiliation: Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taiwan. Electronic address: hunagbs@vghtpe.gov.tw.
authors.forename: Po-Hsun
authors.initials: PH
authors.lastname: Huang
authors.affiliation: Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taiwan; Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Jaw-Wen
authors.initials: JW
authors.lastname: Chen
authors.affiliation: Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Taipei Medical University, Taiwan; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taiwan.
authors.forename: Shing-Jong
authors.initials: SJ
authors.lastname: Lin
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000671:Amputation, Surgical / Q000706:statistics & numerical data*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000517:prevention & control; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007866:Leg / Q000601:surgery; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000188:drug therapy / Q000209:etiology* / Q000517:prevention & control; D057216:Propensity Score; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors
keywords: Dipeptidyl peptidase-4 inhibitors; Peripheral arterial disease; Type 2 diabetes mellitus