Use of Glucagon-Like-Peptide 1 Receptor Agonists and Risk of Fracture as Compared to Use of Other Anti-hyperglycemic Drugs

Johanna H. M. Driessen, Hein A. W. van Onzenoort, Jakob Starup-Linde, Ronald Henry, Andrea M. Burden, Cees Neef, Joop P. van den Bergh, Peter Vestergaard, Frank de Vries

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a new class of drugs that might have a potential beneficial effect on bone metabolism. Data on the effect of GLP-1 RAs and fracture risk are lacking. The aim of the present study was to investigate the association between the use of GLP-1 and the risk of fracture. A case-control study was performed using Danish National Health Service data. 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 above. Conditional logistic regression estimated the odds ratios (OR) of fracture with current use of DPP4-I use. Analyses were adjusted for comorbidities and recent drug use. Among cases (n = 229,114), there were 6993 current non-insulin anti-diabetic drug (NIAD) users (excluding incretin users) and 255 GLP-1 RA users. Similarly, among controls (n = 229,114), 7209 were NIAD users (excluding incretin users) and 220 were GLP-1 RA users. Current GLP-1 RA use was not associated with a decreased risk of fracture [adjusted (adj.) OR 1.16; 95 % CI 0.83-1.63]. Osteoporotic fracture risk was also not associated with current GLP-1 RA use (adj. OR 0.78; 95 % CI 0.44-1.39). In our nation-wide case-control study, we identified that the use of GLP-1 RA was not associated with fracture risk as compared to the use of other anti-hyperglycemic drugs. Additionally, current GLP-1 RA use, stratified by cumulative or average daily dose, is not associated with fracture risk. Further research should focus on long-term use of GLP-1 RA and fracture risk.