Abstract
Glucagon-like Peptide-1 receptor agonists (GLP1-ra) are a relatively new class of anti-hyperglycemic drugs which may positively affect bone metabolism and thereby decrease (osteoporotic) bone fracture risk. Data on the effect of GLP1-ra on fracture risk are scarce and limited to clinical trial data only. The aim of this study was to investigate, in a population-based cohort, the association between the use of GLP1-ra and bone fracture risk. We conducted a population-based cohort study, with the use of data from the Clinical Practice Research Datalink (CPRD) database (2007–2012). The study population (N = 216,816) consisted of all individuals with type 2 diabetes patients with at least one prescription for a non-insulin anti-diabetic drug and were over 18 years of age. Cox proportional hazards models were used to estimate the hazard ratio of fracture in GLP1-ra users versus never-GLP1-ra users. Time-dependent adjustments were made for age, sex, lifestyle, comorbidity and the use of other drugs. There was no decreased risk of fracture with current use of GLP1-ra compared to never-GLP1-ra use (adjusted HR 0.99, 95 % CI 0.82–1.19). Osteoporotic fracture risk was also not decreased by current GLP1-ra use (adjusted HR 0.97; 95 % CI 0.72–1.32). In addition, stratification according to cumulative dose did not show a decreased bone fracture risk with increasing cumulative GLP1-ra dose. We showed in a population-based cohort study that GLP1-ra use is not associated with a decreased bone fracture risk compared to users of other anti-hyperglycemic drugs. Future research is needed to elucidate the potential working mechanisms of GLP1-ra on bone.
Highlights
In individuals with type 2 diabetes, the risk of bone fracture is increased compared to individuals without type 2 diabetes [1]
We showed in a population-based cohort study that Glucagon-like Peptide-1 receptor agonists (GLP1-ra) use is not associated with a decreased bone fracture risk compared to users of other antihyperglycemic drugs
GLP1-ra users were younger than never-GLP1-ra users (53.5 vs. 61.0 years), and had a higher body mass index (BMI) (37.5 vs. 31.0)
Summary
In individuals with type 2 diabetes, the risk of bone fracture is increased compared to individuals without type 2 diabetes [1]. This increased risk might be associated with the pathobiology of type 2 diabetes itself, the underlying mechanisms remain largely unknown [2]. It has been suggested that this increased bone fracture risk is a consequence of the kind of therapeutic regimen initiated to combat hyperglycemia [3]. Thiazolidinediones [4,5,6] have shown to increase. M. Driessen et al.: Bone Fracture Risk is Not Associated with the Use of Glucagon-Like
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