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Peer-reviewedCC BY-NC 4.0Osteoporosis International

Lower fall and femoral fracture risks with semaglutide and tirzepatide compared with DPP-4 inhibitors in older adults with type 2 diabetes

  • Hsin-Yu Chen1
  • Jheng-Yan Wu2
  • Yi-Hsin Chu1
  • Tse-Wei Chen3
  • Chun-Feng Huang1,4,5,6
6 affiliations
  1. 1Department of Family Medicine, Chi Mei Medical Center, Tainan, Taiwan
  2. 2Department of Nutrition, Chi Mei Medical Center, Tainan, Taiwan
  3. 3Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
  4. 4Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
  5. 5Department of Leisure Services Management, Chaoyang University of Technology, Taichung, Taiwan
  6. 6School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan
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Abstract

This retrospective cohort study evaluated whether semaglutide and tirzepatide reduce the risk of falls and femoral fractures in older adults with type 2 diabetes and overweight or obesity. The findings showed significantly lower risks of both outcomes compared with DPP-4 inhibitors.

Purpose: Incretin-based therapies may influence musculoskeletal health. This study evaluated the association of semaglutide and tirzepatide with femoral fractures and falls in older adults with type 2 diabetes (T2DM) and overweight or obesity.

Methods: This retrospective cohort study using the TriNetX database (2018–2025) included adults aged ≥ 65 with T2DM and BMI ≥ 25 kg/m2. Patients receiving semaglutide or tirzepatide were compared with those on dipeptidyl peptidase-4 (DPP-4) inhibitors using 1:1 propensity score matching. Primary and secondary outcomes were 1-year femoral fracture and falls, respectively.

Results: After matching, 27,896 patients were included in the semaglutide/DPP-4 comparison and 12,808 in the tirzepatide/DPP-4 comparison. Femoral fractures were significantly lower with semaglutide (0.3% vs. 0.5%; HR 0.488; 95% CI 0.367–0.649; P < 0.0001) and tirzepatide (0.2% vs. 0.4%; HR 0.452; 95% CI 0.280–0.729; P = 0.0008) compared with DPP-4 inhibitors. Fall risk was also reduced for both semaglutide (3.6% vs. 5.4%; HR 0.663; 95% CI 0.612–0.718; P < 0.0001) and tirzepatide (3.6% vs. 5.7%; HR 0.664; 95% CI 0.591–0.747; P < 0.0001). Subgroup analyses showed consistent fall reduction across categories, while fracture reduction was more pronounced in patients with BMI ≥ 30 kg/m2.

Conclusion: In older adults with T2DM and overweight/obesity, semaglutide and tirzepatide were associated with significantly lower risks of femoral fracture and falls compared with DPP-4 inhibitors, suggesting musculoskeletal benefits beyond glycemic control.

Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00198-026-08134-y.

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Cite

BibTeXRIS
BibTeX
@article{chen2026lower,
  title = {{Lower fall and femoral fracture risks with semaglutide and tirzepatide compared with DPP-4 inhibitors in older adults with type 2 diabetes}},
  author = {Hsin-Yu Chen and Jheng-Yan Wu and Yi-Hsin Chu and Tse-Wei Chen and Chun-Feng Huang},
  journal = {Osteoporosis International},
  year = {2026},
  month = jul,
  doi = {10.1007/s00198-026-08134-y},
  url = {https://doi.org/10.1007/s00198-026-08134-y},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Lower fall and femoral fracture risks with semaglutide and tirzepatide compared with DPP-4 inhibitors in older adults with type 2 diabetes
AU  - Hsin-Yu Chen
AU  - Jheng-Yan Wu
AU  - Yi-Hsin Chu
AU  - Tse-Wei Chen
AU  - Chun-Feng Huang
PY  - 2026
DA  - 2026/07/11
JO  - Osteoporosis International
DO  - 10.1007/s00198-026-08134-y
UR  - https://doi.org/10.1007/s00198-026-08134-y
AB  - This retrospective cohort study evaluated whether semaglutide and tirzepatide reduce the risk of falls and femoral fractures in older adults with type 2 diabetes and overweight or obesity. The findings showed significantly lower risks of both outcomes compared with DPP-4 inhibitors.  Purpose: Incretin-based therapies may influence musculoskeletal health. This study evaluated the association of semaglutide and tirzepatide with femoral fractures and falls in older adults with type 2 diabetes (T2DM) and overweight or obesity.  Methods: This retrospective cohort study using the TriNetX database (2018–2025) included adults aged ≥ 65 with T2DM and BMI ≥ 25 kg/m2. Patients receiving semaglutide or tirzepatide were compared with those on dipeptidyl peptidase-4 (DPP-4) inhibitors using 1:1 propensity score matching. Primary and secondary outcomes were 1-year femoral fracture and falls, respectively.  Results: After matching, 27,896 patients were included in the semaglutide/DPP-4 comparison and 12,808 in the tirzepatide/DPP-4 comparison. Femoral fractures were significantly lower with semaglutide (0.3% vs. 0.5%; HR 0.488; 95% CI 0.367–0.649; P < 0.0001) and tirzepatide (0.2% vs. 0.4%; HR 0.452; 95% CI 0.280–0.729; P = 0.0008) compared with DPP-4 inhibitors. Fall risk was also reduced for both semaglutide (3.6% vs. 5.4%; HR 0.663; 95% CI 0.612–0.718; P < 0.0001) and tirzepatide (3.6% vs. 5.7%; HR 0.664; 95% CI 0.591–0.747; P < 0.0001). Subgroup analyses showed consistent fall reduction across categories, while fracture reduction was more pronounced in patients with BMI ≥ 30 kg/m2.  Conclusion: In older adults with T2DM and overweight/obesity, semaglutide and tirzepatide were associated with significantly lower risks of femoral fracture and falls compared with DPP-4 inhibitors, suggesting musculoskeletal benefits beyond glycemic control.  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00198-026-08134-y.
SN  - 0937-941X
SN  - 1433-2965
ER  -