Dipeptidyl peptidase-4 inhibitors attenuates osteoporosis in patients with diabetes: A nationwide, retrospective, matched-cohort study in Taiwan

J Chin Med Assoc. 2022 Jul 1;85(7):747-753. doi: 10.1097/JCMA.0000000000000743. Epub 2022 Jun 30.

Abstract

Background: Patients with diabetes have a relatively high risk of fracture due to osteoporosis. However, the risk of osteoporosis associated with the use of oral hypoglycemic drugs and dipeptidyl peptidase-4 inhibitor (DPP-4i) by patients with diabetes is unclear. This study aimed to explore the effect of DPP-4i on the risk of osteoporosis in Taiwanese patients with type 2 diabetes mellitus (T2DM).

Methods: This study enrolled 6339 patients on DPP-4i (DPP-4i group) and 25 356 patients without DPP-4i (non-DPP-4i group). They were matched by 1:4 propensity score matching, using confounding variables including sex, age, comorbidities, medication, and index year. Cox proportional hazards analysis was used to compare hospitalization and mortality during an average follow-up period of 7 years.

Results: The mean age of patients in the two groups was 66 years. Men were slightly higher in number (51.79%) than women. At the end of the follow-up period, 113 (0.36%) patients had osteoporosis, of which 15 (0.24%) were in the case group and 98 (0.39%) in the control group. The risk of all-cause osteoporosis was significantly lower in the DPP-4i group than in the non-DPP-4i group (adjusted hazard ratio [HR] 0.616; 95% confidence interval [CI] 0.358-0.961; p = 0.011). Kaplan-Meier analysis showed that the preventive effect on osteoporosis was positively correlated with the cumulative dose of DPP-4i (log-rank, p = 0.039) with the class effect.

Conclusion: Compared with not using DPP-4i, the use of DPP-4i in Taiwanese T2DM patients was associated with a lower risk of osteoporosis due to the class effect, and the preventive effect was dose-dependent. However, larger prospective studies are needed to validate this finding and to explore the possible mechanism of the preventive effect of DPP-4i.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cohort Studies
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Dipeptidyl-Peptidase IV Inhibitors* / therapeutic use
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / therapeutic use
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Osteoporosis* / etiology
  • Osteoporosis* / prevention & control
  • Retrospective Studies
  • Taiwan

Substances

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