JAMA Network Open · IF 10.5 · July 24, 2026 · LoE II
Glucagon-Like Peptide-1 Receptor Agonists and Fragility Fracture Risk in Type 2 Diabetes
Christopher D. Hamad, Joshua Wiener, Autreen Golzar, Kaur Hp, Carolyn Henein, Andrew P. Kittredge, Gabriel Su, David C. Kaelber, Liana Chan, Michael R. Yeaman, J Y Adams, Nicholas M. Bernthal — University of California, Los Angeles
This retrospective study used US electronic health records to compare 66,803 propensity-matched pairs of adults with type 2 diabetes who started either a GLP-1 receptor agonist (like semaglutide or liraglutide) or a DPP-4 inhibitor. Over 3 years, patients starting a GLP-1 RA had a 21% lower relative risk of fragility fracture than those starting a DPP-4i (hazard ratio 0.79), with the largest protection seen for vertebral and hip fractures, and this benefit appeared independent of weight loss or blood sugar changes. However, the protective effect faded by year 3, and in a separate analysis GLP-1 RA use was actually associated with higher fracture risk in people without diabetes.
AI summary · from the full text · reviewed by Pukhraj Gaheer, Medical Student, Queen's University before publishing
Why it mattersOrthopedic surgeons increasingly manage fragility fractures in an aging population on GLP-1 receptor agonists, and this large observational signal raises the question of whether these drugs affect bone health differently than assumed.
Conclusion strengthInconclusive
Statistically significant, but the whole 95% CI 0.76 to 0.83 sits below a 25% relative reduction — real but clinically trivial.
Presenting this at rounds? Start here
- ?This is a retrospective, non-randomized comparison using administrative EHR data with no direct measurement of bone mineral density, falls, physical activity, or medication adherence beyond fill counts; how much could residual confounding (E-value 1.83) explain an HR of 0.79?
- ?If GLP-1 RAs are confirmed to lower fracture risk in patients with diabetes but not in those without it, should orthopedic surgeons or endocrinologists factor fracture risk into the decision to prescribe GLP-1 RAs versus other second-line diabetes agents?