What is the clinical evidence from this study?

Study design: Cohort. Population: Type 2 diabetes mellitus and overweight or obesity (n=81408). Intervention: Semaglutide vs. DPP-4 inhibitors. Primary outcome: Femoral fracture within 1 year (HR 0.488, 95% CI 0.367-0.649, p=<0.0001).

What question did this study set out to answer?

The study aimed to evaluate the effects of semaglutide and tirzepatide on fall and femoral fracture risks in older adults with type 2 diabetes.

July 12, 2026Osteoporosis International0 citationsOpen Access

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

Q: What are the key findings of this study?

Semaglutide and tirzepatide significantly reduced the 1-year risk of femoral fractures (HR 0.488 and HR 0.452, respectively) compared with DPP-4 inhibitors in older adults with type 2 diabetes.

Q: What question did this study set out to answer?

The study aimed to evaluate the effects of semaglutide and tirzepatide on fall and femoral fracture risks in older adults with type 2 diabetes.

HCHsin-Yu Chen JWJM Wu YCYi-Hsin Chu

Key Result

Semaglutide and tirzepatide significantly reduced the 1-year risk of femoral fractures (HR 0.488 and HR 0.452, respectively) compared with DPP-4 inhibitors in older adults with type 2 diabetes.

Key Points

The study aimed to evaluate the effects of semaglutide and tirzepatide on fall and femoral fracture risks in older adults with type 2 diabetes.
Retrospective cohort study using the TriNetX database over the period 2018-2025.
Included adults aged ≥ 65 with type 2 diabetes and BMI ≥ 25 kg/m2, comparing semaglutide and tirzepatide to DPP-4 inhibitors.
Employed 1:1 propensity score matching, including 27,896 patients for semaglutide and 12,808 for tirzepatide comparisons.
Semaglutide users had femoral fractures of 0.3% compared to 0.5% for DPP-4 inhibitors (HR 0.488; 95% CI 0.367–0.649; P < 0.0001).
Tirzepatide users had femoral fractures of 0.2% compared to 0.4% for DPP-4 inhibitors (HR 0.452; 95% CI 0.280–0.729; P = 0.0008).
Both treatments significantly reduced fall risk: semaglutide (3.6% vs. 5.4%; HR 0.663; P < 0.0001) and tirzepatide (3.6% vs. 5.7%; HR 0.664; P < 0.0001).

Study Design

Type

Cohort (n=81,408)

Multicenter

Yes

Structured PICO

Do semaglutide and tirzepatide reduce the risk of femoral fractures and falls in older adults with type 2 diabetes and overweight or obesity compared with DPP-4 inhibitors?

Population

81,408 older adults (aged ≥ 65 years) with type 2 diabetes and overweight or obesity, followed for 1 year.

Exposure

Semaglutide or tirzepatide

Comparator

Dipeptidyl peptidase-4 (DPP-4) inhibitors (1:1 propensity score matching)

Outcome

1-year femoral fracturehard clinical

In older adults with T2DM and overweight/obesity, semaglutide and tirzepatide are associated with significantly lower risks of femoral fractures and falls compared with DPP-4 inhibitors.

Main Result

Hazard Ratio: 0.488 (95% CI 0.367–0.649)

Absolute Event Rate: 0.3% vs 0.5%

Number Needed to Treat: 372

p-value: p=<0.0001

Limitations

Observational retrospective design with potential residual confounding
Lack of detailed clinical information such as bone mineral density, body composition, and frailty assessments
Medication adherence and dosing differences could not be fully evaluated
On-treatment analytical approach may introduce selection bias
One-year follow-up may not fully capture long-term skeletal effects
Potential ascertainment bias for the fall outcome
Residual imbalance in the tirzepatide cohort for HbA1c and systolic blood pressure

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. 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. This retrospective cohort study using the TriNetX database (2018–2025) included adults aged ≥ 65 with T2DM and BMI ≥ 25 kg/m 2 . 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. 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/m 2 . 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.

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Cite This Study

Chen et al. (Sat,) conducted a cohort in Type 2 diabetes mellitus and overweight or obesity (n=81,408). Semaglutide vs. DPP-4 inhibitors was evaluated on Femoral fracture within 1 year (HR 0.488, 95% CI 0.367-0.649, p=<0.0001). Semaglutide and tirzepatide significantly reduced the 1-year risk of femoral fractures (HR 0.488 and HR 0.452, respectively) compared with DPP-4 inhibitors in older adults with type 2 diabetes.

synapsesocial.com/papers/6a534ff4985393734a594d03 https://doi.org/https://doi.org/10.1007/s00198-026-08134-y

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