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 database study used TriNetX electronic health records to compare fragility fracture risk in about 133,600 propensity-matched adults with type 2 diabetes who started a GLP-1 receptor agonist versus a DPP-4 inhibitor. Over 3 years, fragility fractures occurred in 2,030 GLP-1 RA users versus 2,484 DPP-4i users, corresponding to a 21% lower relative risk (HR 0.79) that appeared independent of weight loss or glucose control, though the effect weakened by year 3 and was not seen in patients without diabetes.
AI summary · from the full text · reviewed by Pukhraj Gaheer, Medical Student, Queen's University before publishing
Why it mattersOrthopaedic surgeons are increasingly seeing patients on GLP-1 RAs and need to know whether these drugs raise or lower fragility fracture risk, especially since weight loss itself is a known risk factor.
Conclusion strengthInconclusive
Contradicts current practice and patient-important outcome, offset by only 36 months of follow-up and more patients lost than the result can absorb.
Presenting this at rounds? Start here
- ?Given this is a retrospective, non-randomized comparison using administrative EHR data with unmeasured confounders like physical activity, fall risk, and baseline bone mineral density, how much can propensity-score matching really substitute for randomization here?
- ?If you were counseling a patient with T2D and osteopenia who is starting a GLP-1 RA, would this study change how you approach bone health monitoring, and why or why not?