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GLP-1 Receptor Agonists Increase Fracture Risk in Patients with Obesity
Evangelia Constantine, BS1; Luke F Enthoven, BS2; Riley Hart Kahan, MBS2; Emily Michelle Pflug, MD3; Alexander Lauder, MD3
1University of Colorado Anschutz, Aurora, CO; 2University of Colorado Anschutz Medical Campus, Aurora, CO; 3University of Colorado, Aurora, CO

Introduction

GLP-1 receptor agonists (GLP-1 RA) promote insulin secretion and satiety. This class of medication is prescribed to improve glycemic control in patients with type 2 diabetes mellitus (T2DM). These medications also have potential to promote weight loss. Pre-clinical trials suggested that GLP-1 RAs may induce osteoblast stimulation, and thus may decrease the risk of fracture. The effect of GLP-1 RAs on bone health in patients without T2DM has not been studied. However, significant rapid weight loss can be associated with decreased muscle mass, which may increase fracture risk. The purpose of this study was to assess fracture risk in obese patients without diabetes following GLP-1 RA use.

Methods:

A retrospective study was conducted using de-identified data from the TriNetX. Patients were included based on the diagnosis of obesity between 2018-2022. Patients with diabetes or A1c >6.5 were excluded. Those with fragility fracture risk were excluded including alcohol or nicotine dependence, osteoporosis, rheumatoid arthritis, chronic kidney disease, or chronic use of systemic corticosteroids. An initial query resulted in 1,155,496 patients. Patients with missing demographic factors were excluded, resulting in 606,364 for analysis. This cohort was divided into two groups: (1) those prescribed GLP-1 RA (n = 28,982) and (2) those without GLP-1 RA prescription (n = 577,382). Multiple GLP-1 RAs were included (semaglutide, liraglutide, exenatide, dulaglutide, tirzepatide, and lixisenatide). Propensity score matching was performed for two groups of 29,982 . The primary outcome was fracture diagnosis within the years 2022-2023 following GLP-1 RA prescription. Fracture incidence was compared. Risk and odds ratio with 95% CI's were estimated using multiple logistic regression to account for covariate variability.

Results:

The incidence of fracture was significantly increased in patients with obesity without diabetes who were prescribed a GLP-1 RA (3.27%) compared to patients who were not (2.14%) (RR 1.56 CI [1.42, 1.72]). There was no significant association between GLP-1 RA prescription status and fracture pattern, including hand and wrist (Figure1).


Conclusions:

The use of GLP-1 RAs are associated with an increased fracture risk in obese patients without diabetes. These results contradict previous studies which suggested a protective effect on fracture risk in patients with T2DM who are prescribed GLP-1 RAs. Further research is necessary to guide the prescription of GLP-1 RAs in the setting of obesity.
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