Skeletal effect of semaglutide and tirzepatide in patients with increased risk of fractures
Authors' conclusion
SEM/TIR use was associated with greater annualized TH bone loss in patients without DM, whereas TH bone loss was comparable between GLP-1 RA and controls in patients with DM. These findings suggest GLP-1 RA's effects on bone may differ by DM status, with weight loss driving bone loss in patients without DM.
Study context
- Population
- Adults using semaglutide (SEM)/tirzepatide (TIR) with DXA before initiation and ≥6 months after; GLP-1 RA group 92% female, mean age 64 ± 9 years, BMI 31.0 ± 5.6 kg/m²matched cohort
- Participants
- 255 vs 255
- Exposure
- SEM/TIR use vs matched nonusers
- GLP-1 RAn = 255
- Controlsn = 255reference
- Outcome
- Percentage change in total hip (TH) BMD
- Follow-up
- Median 17 months
Methodological detailssingle-centre, matched by age, sex, BMI and diabetes mellitus (DM)
- Single-centre
- Matched by age, sex, BMI and DM
Main finding
As reported in the abstract
Percentage change in TH BMD · median 17 months
- Both groups had significant declines in bone mineral density (BMD) at total hip (TH) and FN, with a similar magnitude between groups
- Matched cohort
Observational data: associations, not effects.
Further findings
| Outcome | GLP-1 RA | Controls | P value |
|---|---|---|---|
| TH bone loss, patients without DMGreater TH bone loss with GLP-1 RA | −1% | −0.6% | P = 0.04 |
- Weight loss in GLP-1 RA group · median 17 months
- 5% · median
Association of weight loss with bone loss in GLP-1 RA group
- Correlation, TH
- r = 0.32
- Correlation, FN
- r = 0.17
- P (both)
- P < 0.01
TH bone loss, patients with DM
- TH bone loss was similar between groups among patients with DM
Original publication
Skeletal effect of semaglutide and tirzepatide in patients with increased risk of fractures. J Clin Endocrinol Metab. Published 8 February 2026. doi:10.
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