Risk of fracture with sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes: an updated meta-analysis of randomized controlled trials.

Background: Type 2 diabetes mellitus (T2DM) increases the risk of fractures. This meta-analysis compared the effects of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and dipeptidyl peptidase-4 inhibitors (DPP-4i) on fracture risk in patients with T2DM.

Method: A systematic search of PubMed, Web of Science, Embase, and Google Scholar was conducted up to August 6, 2023. Seven cohort studies (n = 1,199,267 participants at baseline; n = 357,119 after propensity matching) comparing SGLT-2i use with DPP-4i use and reporting fracture outcomes were included. Data were extracted and analyzed using a random-effects model. Subgroup analyses were performed by age (<70 and ≥70 years) and sex.

Results: In general, SGLT-2i therapy was linked to reduced fracture risk when compared to DPP-4i (OR: 0.89, 95% CI: 0.81-0.98). Heterogeneity was high (I² = 64.3%). Upon stratified analysis by age, no statistically significant difference was observed between the fracture risk in the <70 years and ≥70 years subgroups upon comparison of SGLT-2i with DPP-4i. No significant difference was also observed in the female subgroup.

Conclusion: This meta-analysis indicates SGLT-2i therapy could be linked with reduced overall fracture risk in comparison to DPP-4i in the general population of T2DM. The benefit was not seen in subgroup analysis based on age and sex. Additional research, ideally with increased cases within subgroups, is required to determine the impact of these drugs on fracture risk in patient subgroups.