ECTS Abstracts (2015) 1 OC4.6

Meta-analysis of observational studies on the effect of incretin treatment on fracture risk

Johanna Driessen1, Andrea Burden1, Hein van Onzenoort3, Ronald Henry4,7, Peter Vestergaard5,6 & Frank de Vries1,2


1Utrecht Institute of Pharmaceutical Sciences, Utrecht, The Netherlands; 2Care and Public Health Research Institute (CAPHRI), Maastricht, The Netherlands; 3Department of Pharmacy, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; 4Department of Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands; 5Clinical Institute, Aalborg University, Aalborg, Denmark; 6Department of Endocrinology, Aalborg University, Aalborg, Denmark; 7Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands.


Background: In Europe, ~60 million patients suffer from type 2 diabetes mellitus (T2DM). T2DM patients are at increased risk of fracture. Incretin agents are used to treat T2DM, and they include two classes: glucagon-like-peptide 1 receptor agonists (GLP1-RAs) and dipeptidyl peptidase-4 inhibitors (DPP4-Is). Currently, there is no data available from electronic healthcare databases. The objective of this study was to evaluate the association between incretin agents and risk of fracture.

Methods: We used data from the UK Clinical Practice Research Datalink (CPRD), the world’s largest primary care database, representative for the total UK population (2007–2012, n=13 million) and from the full country of Denmark (2007–2011, n=5.5 million). We used a cohort design and Cox regression analysis with CPRD data and a case–control study with conditional logistical regression in Denmark (which comprised all patients with a first fracture matched to controls). We compared current incretin use with non-use. A meta-analysis extracted hazard- (HRs) and odds ratios and their corresponding 95% CIs using generic inverse variance methods assuming a random effects model.

Results: Use of incretin agents was not associated with fracture risk in both countries (adj. pooled risk ratio DPP4-I and GLP1-ra: 1.01; 95% CI 0.92–1.12, 1.03; 95% CI 0.87–1.22, respectively). Increasing cumulative dose did not further decrease risk of fracture yielding adj. HRs of 1.07; 95% CI 0.90–1.27 (0–18.2 mg) adj. HR 0.84; 95% CI 0.67–1.06 (18.3–36.5 mg) adj. HR 1.05; 95% CI 0.81–1.37 (36.6–54.7 mg), adj. HR 0.97; 95% CI 0.78–1.20 (>54.7 mg).

Discussion: Use of incretin agents was not associated with fracture risk in both countries, and higher cumulative dosages did not result in an inverse association. Our results do not support the conduct of further clinical research to study beneficial effects of incretin agents on fracture risk.

Disclosure: The authors declared no competing interests.

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