Sulfonylureas and fracture risk in patients with type 2 diabetes mellitus: a systematic review and meta-analysis

Xu, L.; Yuan, R.; Yue, H.; Wang, M.; Cai, W.

doi:10.1016/j.rceng.2026.502596

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Abstract

Objective

To evaluate the association between sulfonylureas and fracture risk in patients with type 2 diabetes mellitus (T2DM).

Methods

PubMed, Web of Science, the Cochrane Library and Embase were systematically searched for observational studies evaluating sulfonylurea-associated fracture risk in patients with T2DM. Pooled relative risk (RR) and its 95% confidence interval (CI) were calculated.

Results

Twelve observational studies involving 5,854,139 patients were included. Sulfonylurea use was significantly associated with increased risks of overall fractures (RR = 1.28; 95% CI: 1.11–1.47) and osteoporotic fractures (RR = 1.38; 95% CI: 1.05–1.80). Site-specific analyses revealed a 23% increase in hip fracture risk (RR = 1.23; 95% CI: 1.03–1.46) and a 47% increase in vertebral fracture risk (RR = 1.47; 95% CI: 1.24–1.74). Fracture risk profiles varied across sulfonylurea subtypes.

Conclusion

Sulfonylureas are associated with a significant increase in the overall risk of fractures and the risk of osteoporotic fractures in patients with T2DM, and this risk is particularly prominent in hip and vertebral fractures.

Keywords:

Sulfonylureas

Type 2 diabetes mellitus

Fracture risk

Meta-analysis

Resumen

Objetivo

Evaluar la asociación entre el uso de sulfonilureas y el riesgo de fracturas en pacientes con diabetes mellitus tipo 2 (DMT2).

Métodos

Se realizaron búsquedas sistemáticas en PubMed, Web of Science, Cochrane Library y Embase de estudios observacionales que evaluaran el riesgo de fracturas asociado a las sulfonilureas en pacientes con DMT2. Se calcularon el riesgo relativo (RR) agrupado y su intervalo de confianza (IC) del 95%.

Resultados

Se incluyeron 12 estudios observacionales con un total de 5.854.139 pacientes. El uso de sulfonilureas se asoció significativamente con un mayor riesgo de fracturas generales (RR = 1,28; IC 95%: 1,11–1,47) y fracturas osteoporóticas (RR = 1,38; IC 95%: 1,05–1,80). Los análisis por sitio específico revelaron un aumento del 23% en el riesgo de fractura de cadera (RR = 1,23; IC 95%: 1,03–1,46) y un aumento del 47% en el riesgo de fractura vertebral (RR = 1,47; IC 95%: 1,24–1,74). Los perfiles de riesgo de fractura variaron según los subtipos de sulfonilureas.

Conclusión

Las sulfonilureas se asocian con un aumento significativo del riesgo general de fracturas y del riesgo de fracturas osteoporóticas en pacientes con DMT2, siendo este riesgo especialmente pronunciado en las fracturas de cadera y vertebrales.

Palabras clave:

Sulfonilureas

Diabetes mellitus tipo 2

Riesgo de fractura

Meta-análisis

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