Association of metformin use with fracture risk in type 2 diabetes: A systematic review and meta-analysis of observational studies

Front Endocrinol (Lausanne). 2023 Jan 11:13:1038603. doi: 10.3389/fendo.2022.1038603. eCollection 2022.

Abstract

Aims: Increasing evidence suggests that metformin can affect bone metabolism beyond its hypoglycemic effects in diabetic patients. However, the effects of metformin on fracture risk in type 2 diabetes mellitus (T2DM) patients remain unclear. A systematic review and meta-analysis were performed in this study to evaluate the association between metformin application and fracture risk in T2DM patients based on previous studies published until June 2021.

Methods: A systematic search was performed to collect publications on metformin application in T2DM patients based on PubMed, Embase, Cochran, and Web of Science databases. Meta-analysis was performed by using a random-effects model to estimate the summary relative risks (RRs) with 95% confidence intervals (CIs). Subgroup analyses based on cohort/case-control and ethnicity and sensitivity analyses were also performed.

Results: Eleven studies were included in the meta-analysis. Results demonstrated metformin use was not significantly associated with a decreased risk of fracture (RR, 0.91; 95% CI, 0.81-1.02; I2 = 96.8%). Moreover, metformin use also demonstrated similar results in subgroup analyses of seven cohort studies and four case-control studies, respectively (RR, 0.90; 95% CI, 0.76-1.07; I2 = 98.0%; RR, 0.96; 96% CI, 0.89-1.03; I2 = 53.7%). Sensitivity analysis revealed that there was no publication bias.

Conclusion: There was no significant correlation between fracture risk and metformin application in T2DM patients. Due to a limited number of existing studies, further research is needed to make a definite conclusion for clinical consensus.

Keywords: bone; diabetes; fracture; meta-analysis; metformin.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diabetes Mellitus, Type 2* / chemically induced
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Fractures, Bone* / epidemiology
  • Fractures, Bone* / etiology
  • Fractures, Bone* / prevention & control
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Metformin* / therapeutic use
  • Risk

Substances

  • Metformin
  • Hypoglycemic Agents

Grants and funding

This research was funded by grants from the National Natural Science Foundation of China (No. 81703584), The regional joint fund of natural science foundation of Guangdong province (No. 2020B1515120052), Guangdong Province Natural Science Foundation of China (No. 2017A030310614, 2021A1515010975), Discipline construction project of Guangdong Medical University (No. 4SG22002G, 4SG21156G, and CLP2021B012), Shenzhen International Collaborative Project (No. GJHZ20200731095009028), Special Funds for Scientific Technological Innovation of Undergraduates in Guangdong Province (No. pdjh2022a0214), the Discipline Construction Fund of Central People’s Hospital of Zhanjiang (No. 2022A09), Guangdong Medical University scientific research fund (No. B2017001). The Science and Technology Foundation of Zhanjiang, Guangdong Province, China (No. 2022A01099).