Evidence mapPaperPMID 42496972Full record

ArticleJAMA network open2026

Glucagon-Like Peptide-1 Receptor Agonists and Fragility Fracture Risk in Type 2 Diabetes.

Christopher D Hamad, Joshua Wiener, Autreen Golzar, Harlene Kaur, Carolyn Henein, Andrew P Kittredge, Gabriel Su, David C Kaelber, Liana Chan, Michael R Yeaman and 3 more

Abstract read
In one paragraph

Article in JAMA network open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Christopher D HamadDepartment of Orthopaedic Surgery, University of California, Los Angeles.
Joshua WienerDepartment of Orthopaedic Surgery, University of California, Los Angeles.
Autreen GolzarDavid Geffen School of Medicine, University of California, Los Angeles.
Harlene KaurUniversity of Massachusetts Chan Medical School, Worcester.
Carolyn HeneinThe University of Texas Medical Branch Galveston School of Medicine, Galveston.
Andrew P KittredgeThe University of California, Los Angeles.
Gabriel SuThe University of California, Los Angeles.
David C KaelberDepartment of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio.
Liana ChanDivision of Infectious Diseases, Department of Medicine, Harbor-UCLA Medical Center, Research and Education Institute at Harbor-UCLA, Torrance, California.
Michael R YeamanDivision of Infectious Diseases, Department of Medicine, Harbor-UCLA Medical Center, Research and Education Institute at Harbor-UCLA, Torrance, California.
John S AdamsDepartment of Orthopaedic Surgery, University of California, Los Angeles.
Nicholas M BernthalDepartment of Orthopaedic Surgery, University of California, Los Angeles.
William L SheppardDepartment of Orthopaedic Surgery, University of California, Los Angeles.

Funding

Regenerative Musculoskeletal Medicine Training ProgramT32AR059033 · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2025 to 2025
$459k
NIAMS NIH HHS T32 AR059033
6 · The paper itself

Abstract

Importance: Obesity, type 2 diabetes (T2D), and weight loss are associated with increased fragility fracture risk. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely prescribed, yet their effects on skeletal outcomes remain uncertain. Objective: To evaluate the association between GLP-1 RA initiation and 3-year fragility fracture risk compared with dipeptidyl peptidase-4 inhibitor (DPP-4i) initiation among adults with T2D. Design, Setting, and Participants: This comparative effectiveness study using retrospective target trial emulation examined data from the TriNetX Research Network (January 1, 2015, to December 31, 2022), a multicenter US electronic health record database. Adults aged 50 to 90 years with T2D who newly initiated a GLP-1 RA or DPP-4i were followed up for up to 3 years. A separate cohort stratified by T2D status was also analyzed. The database was queried on January 26, 2026, to generate a line-level analytic dataset. Exposures: Initiation of GLP-1 RAs vs DPP-4is. Main Outcomes and Measures: The primary outcome was incident fragility fracture, defined as fractures after low-energy trauma (eg, fall from standing height). Cohorts were propensity score matched. Time-varying mediation analyses were used to evaluate the contribution of changes in body mass index and hemoglobin A1c. Results: After matching, 133 606 patients (66 803 per group; GLP-1 RA vs DPP-4i: mean [SD] age 63.2 [8.1] vs 63.8 [8.5] years; 35 195 [52.7%] vs 36 098 [54.0%] male) were included. Initiation of GLP-1 RA was associated with lower fragility fracture risk compared with DPP-4i initiation (hazard ratio [HR], 0.79 [95% CI, 0.76-0.83]; absolute risk reduction, 0.79% [95% CI, 0.60%-0.99%]; number needed to treat, 126 [95% CI, 101-168]). The largest risk reductions were observed with vertebral (HR, 0.68 [95% CI, 0.63-0.73]) and hip or femur (HR, 0.70 [95% CI, 0.63-0.79]) fractures. In a sensitivity analysis stratified by diabetes status, fracture risk reduction was observed among patients with T2D (HR, 0.91 [95% CI, 0.88-0.95]) but not among those without T2D (HR, 1.13 [95% CI, 1.04-1.23]; interaction P < .001). Mediation analyses showed that the direct association between GLP-1 RA use and lower fracture risk persisted (HR, 0.81 [95% CI, 0.76-0.86]). Conclusions and Relevance: This target trial emulation study of adults with T2D found that initiation of a GLP-1 RA was associated with lower 3-year fragility fracture risk compared with initiation of a DPP-4i, independent of changes in body mass index and hemoglobin A1c. Prospective studies are needed to establish causality and define long-term skeletal effects.

Indexed as

Diabetes Mellitus, Type 2Dipeptidyl-Peptidase IV InhibitorsFractures, BoneGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsOsteoporotic FracturesAgedAged, 80 and overFemaleHumansMaleMiddle AgedRetrospective StudiesDipeptidyl-Peptidase IV InhibitorsGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic Agents

Identifiers

PMID42496972
PMCPMC13401206

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.