Association between dipeptidyl peptidase-4 inhibitors and increased risk for bullous pemphigoid within 3 months from first use: A 5-year population-based cohort study using the Japanese National Database

J Diabetes Investig. 2022 Mar;13(3):460-467. doi: 10.1111/jdi.13676. Epub 2021 Oct 11.

Abstract

Aims/introduction: We assessed the association between dipeptidyl peptidase-4 inhibitors (DPP-4is) and bullous pemphigoid (BP) and time-dependent changes in the risk for developing BP after DPP-4i initiation.

Materials and methods: The present population-based, real-world study was carried out using the Japanese National Database dataset collected between 2013 and 2018. To assess independent correlations between DPP-4is and the development of BP, the self-controlled case series method was used.

Results: Among the cohort followed up for a median of 1,540 days, 53,027 patients were likely to develop BP. The possible incidence rate of BP in all 150,328,339 patients was 10.4/100,000 person-years. Among the 9,705,814 patients with type 2 diabetes, 15,634 were likely to develop BP. The possible incidence rate of BP in patients with type 2 diabetes was 38.1/100,000 person-years, whereas that in patients with type 2 diabetes who did and did not use DPP-4is was 40.7 and 30.0/100,000 person-years, respectively. Analysis of the 28,705 patients with type 2 diabetes likely to develop BP after initial DPP-4i use showed a risk ratio of 2.15 (95% confidence interval [CI] 1.75-2.63), 1.70 (95% CI 1.37-2.11), 1.44 (95% CI 1.15-1.82), 1.25 (95% CI 0.98-1.59), 0.84 (95% CI 0.63-1.10), 0.84 (95% CI 0.64-1.11) and 1.05 (95% CI 0.92-1.20), for the risk period of ≤30, 31-60, 61-90, 91-120, 121-150, 151-180 and 181-365 days, respectively.

Conclusions: Although DPP-4is were associated with increased risk for BP, the risk was particularly significant within 3 months from first use.

Keywords: Administrative claims database; Bullous pemphigoid; Dipeptidyl peptidase-4 inhibitors.

MeSH terms

  • Cohort Studies
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / epidemiology
  • Dipeptidyl-Peptidase IV Inhibitors* / adverse effects
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Japan / epidemiology
  • Pemphigoid, Bullous* / chemically induced
  • Pemphigoid, Bullous* / epidemiology

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases