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

Abstract

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.

A Pilot Study Showing Acute Inhibitory Effect of GLP‐1 on the Bone Resorption Marker CTX in Humans

“…Liraglutide treatment was associated with a reduced risk of fractures, whereas exenatide was associated with an increased risk of fractures as compared with placebo or other antidiabetic drugs . However, in a population‐based cohort study, neither liraglutide nor exenatide influenced fracture risk compared with other oral antidiabetic drugs . Similar results were found in a meta‐analysis by Mabilleau and colleagues .…”

Diabetes pharmacotherapy and effects on the musculoskeletal system

“…Exenatide had higher probability of being the safest GLP‐1R agonist with regard to the risk of fracture, followed by dulaglutide, liraglutide, albiglutide, lixisenatide, and semaglutide . Other studies have not found an association between GLP‐1R agonists and fracture risk . These contradictory findings could be related to the difference in the number of trials included in the meta‐analyses, different doses, and duration of therapy with GLP‐1R agonists and different analyses used to report comparisons between GLP‐1R agonists.…”

“…330 331 Other studies have not found an association between GLP-1R agonists and fracture risk. [332][333][334] These contradictory findings could be related to the difference in the number of trials included in the meta-analyses, different doses, and duration of therapy with GLP-1R agonists and different analyses used to report comparisons between GLP-1R agonists. Additionally, recent studies have reported differences in the effects on the gastrointestinal and cardiovascular system with use of short-acting and long-acting GLP-1R agonists.…”

Diabetes, bone and glucose-lowering agents: clinical outcomes

“…However, this appears to have been a chance finding as subsequent meta-analyses, incorporating additional RCTs, found no evidence of an effect of DPP-4 inhibitor therapy on fractures [59,60]. For example, the largest published meta-analysis included 62 RCTs of DPP-4 inhibitor therapies with 722 fractures and reported a relative risk of 0.95 (95% CI [62,63]. Additional studies are needed to clarify the effects of the GLP-1 receptor agonists on fracture risk.…”