Use of dipeptidyl peptidase 4 inhibitors and fracture risk compared to use of other anti-hyperglycemic drugs

Pharmacoepidemiol Drug Saf. 2015 Oct;24(10):1017-25. doi: 10.1002/pds.3837. Epub 2015 Jul 16.


Introduction: Dipeptidyl peptidase-4 inhibitors (DPP4-Is) are a new class of anti-hyperglycemic drugs which might have a potential beneficial effect on bone metabolism. Data on the effect of DPP4-I use and fracture risk is limited and conflicting. The aim of the present study was to investigate the association between use of DPP4-Is and fracture risk.

Methods: A case-control study was conducted using data from the Danish National Health Service. Cases were those who sustained a fracture, and controls were those without a fracture during the study period (2007-2011), all aged 18 years and older. Conditional logistic regression estimated the odds ratios of fracture with current use of DPP4-I use. Analyses were adjusted for comorbidities and recent drug use.

Results: Among the cases there were 6993 current non-insulin anti-diabetic drug (NIAD) users (excluding incretin users) and 643 DPP4-I users. There were 7209 NIAD users (excluding incretin users) among the controls and 707 DPP4-I users. Current DPP4-I use was not associated with risk of any fracture (adjusted [adj.] OR: 0.97, 95% CI: 0.79-1.18) or major osteoporotic fracture (adj. OR: 0.96, 95% CI: 0.72-1.28). Stratification of current DPP4-I use to cumulative and average daily dose did not show an association.

Conclusions: In a population-based case-control study we identified that short-term use of DPP4-I was not associated with fracture risk as compared to users of other anti-hyperglycemic drugs. Additionally, results suggest that increasing daily dose and cumulative DPP4-I exposure were not associated with fracture risk. However, more research is needed to assess the effect of long-term DPP4-I use on the risk of fracture.

Keywords: DPP4-I; case-control; fracture; pharmacoepidemiology; type 2 diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Confounding Factors, Epidemiologic
  • Denmark / epidemiology
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / epidemiology
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Dose-Response Relationship, Drug
  • Female
  • Fractures, Bone / epidemiology*
  • Fractures, Bone / etiology
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects*
  • Hypoglycemic Agents / therapeutic use
  • Logistic Models
  • Male
  • Middle Aged
  • Risk
  • Time Factors
  • Young Adult


  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents