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Association between combined treatment with SGLT2 inhibitors and metformin for type 2 diabetes mellitus on fracture risk: a meta-analysis of randomized controlled trials

Abstract

Summary

This study analyzed the effects of combination therapy with sodium-glucose transporter-2 inhibitors (SGLT2is) and metformin on fracture risk. Summarizing available randomized controlled trials, we found that SGLT2is combined with metformin therapy did not influence fracture risk compared with metformin monotherapy or other comparators in patients with T2DM.

Introduction

No study is available evaluating the association between sodium-glucose transporter-2 inhibitors (SGLT2is) in combination with metformin use and fracture risk. Our study aimed to investigate the fracture risk of combination therapy with SGLT2is and metformin in patients with type 2 diabetes mellitus (T2DM).

Methods

PubMed, Embase, ClinicalTrials.gov site, and the Cochrane Library databases were scrutinized for all eligible randomized controlled trials (RCTs). The summarized odds ratios (ORs) and their 95% confidence intervals (CI) were calculated using Review Manager 5.3 software.

Results

A total of 25 RCTs involving 19,500 participants with T2DM were included in our studies. There were 88 fracture cases in the SGLT2is in combination with metformin therapy group and 79 in the control group. SGLT2is combined with metformin use did not influence fracture risk compared with metformin monotherapy or other comparators in patients with T2DM (OR = 0.97, 95% CI 0.71–1.32). After stratification by drug type, follow-up time, control regimen, and type of fracture, the upshots were still stable.

Conclusion

SGLT2is and metformin combination therapy did not influence fracture risk compared with metformin monotherapy or other comparators in patients with T2DM.

Prospero registration number

CRD42020168435.

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Qian, BB., Chen, Q., Li, L. et al. Association between combined treatment with SGLT2 inhibitors and metformin for type 2 diabetes mellitus on fracture risk: a meta-analysis of randomized controlled trials. Osteoporos Int 31, 2313–2320 (2020). https://doi.org/10.1007/s00198-020-05590-y

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Keywords

  • Fracture
  • Meta-analysis
  • Metformin
  • Type 2 diabetes mellitus
  • SGLT2 inhibitor