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Summary <p>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.</p> Purpose <p>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.</p> Methods <p>This retrospective cohort study using the TriNetX database (2018–2025) included adults aged ≥ 65 with T2DM and BMI ≥ 25&#xa0;kg/m<sup>2</sup>. 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.</p> Results <p>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; <i>P</i> &lt; 0.0001) and tirzepatide (0.2% vs. 0.4%; HR 0.452; 95% CI 0.280–0.729; <i>P</i> = 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; <i>P</i> &lt; 0.0001) and tirzepatide (3.6% vs. 5.7%; HR 0.664; 95% CI 0.591–0.747; <i>P</i> &lt; 0.0001). Subgroup analyses showed consistent fall reduction across categories, while fracture reduction was more pronounced in patients with BMI ≥ 30&#xa0;kg/m<sup>2</sup>.</p> Conclusion <p>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.</p>

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

  • 期刊论文

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  • 发表日期：

    2026年7月11日

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  • Hsin-Yu Chen,
  • Jheng-Yan Wu,
  • Yi-Hsin Chu,
  • Tse-Wei Chen,
  • Chun-Feng Huang

摘要

Summary

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.