Risk of bone fractures associated with glucagon-like peptide-1 receptor agonists’ treatment: a meta-analysis of randomized controlled trials

Abstract

Traditional anti-diabetic drugs may have negative or positive effects on risk of bone fractures. Yet the relationship between the new class glucagon-like peptide-1 receptor agonists (GLP-1 RA) and risk of bone fractures has not been established. We performed a meta-analysis including randomized controlled trials (RCT) to study the risk of bone fractures associated with liraglutide or exenatide, compared to placebo or other active drugs. We searched MEDLINE, EMBASE, and clinical trial registration websites for published or unpublished RCTs comparing the effects of liraglutide or exenatide with comparators. Only studies with disclosed bone fracture data were included. Separate pooled analysis was performed for liraglutide or exenatide, respectively, by calculating Mantel-Haenszel odds ratio (MH-OR). 16 RCTs were identified including a total of 11,206 patients. Liraglutide treatment was associated with a significant reduced risk of incident bone fractures (MH-OR=0.38, 95% CI 0.17-0.87); however, exenatide treatment was associated with an elevated risk of incident bone fractures (MH-OR=2.09, 95% CI 1.03-4.21). Publication bias and heterogeneity between studies were not observed. Our study demonstrated a divergent risk of bone fractures associated with different GLP-1 RA treatments. The current findings need to be confirmed by future well-designed prospective or RCT studies.

Adverse Effects of GLP-1 Receptor Agonists

“…A meta-analysis of 16 randomized controlled trials (n = 11,206) assessed the risk of bone fractures associated with liraglutide or exenatide, in comparison to placebo or other active drugs [138]. The administration of liraglutide was associated with a significantly decreased risk of incident bone fractures (MH-OR: 0.38, 95% CI: 0.17-0.87), while exenatide administration was linked with an increased risk (MH-OR: 2.09, 95% CI: 1.03-4.21).…”

DPP-4 inhibitor therapy and bone fractures in people with Type 2 diabetes – A systematic review and meta-analysis

“…Another meta-analysis of RCT studies by Su et al 55 The contrasting results that have emerged from these incretin-based therapy review studies show the need for further investigations into the role of incretin hormones in bone metabolism across various populations. The reason for this disparity between results from previous reviews and this current review study cannot be explained from our data.…”

“…For the users of this treatment, it is good news that DPP-4 inhibitors are not generally associated with fracture incidence, in contrast to thiazolidinedione, which are known to be associated with increased fracture risk, or with exenatide, which was recently shown to be associated with increased risk of bone fracture. 55 The results drawn from RCTs in the field are varied, meaning that a definitive conclusion …”

Novel skeletal effects of glucagon-like peptide-1 (GLP-1) receptor agonists

“…They showed divergent effects on bone fractures and differences among GLP-1RAs. It was demonstrated that liraglutide significantly reduced the risk of bone fractures, whereas exenatide treatment was associated with an elevated risk of incident bone fractures (Su et al 2015). The other meta-analysis however found neutral effect of both liraglutide and exenatide as compared with other anti-diabetic medications (Mabilleau et al 2014).…”