Comparison of the Effects of Metformin and Thiazolidinediones on Bone Metabolism: A Systematic Review and Meta-Analysis

Medicina (Kaunas). 2023 May 8;59(5):904. doi: 10.3390/medicina59050904.

Abstract

Objectives: Studies have shown that people with diabetes have a high risk of osteoporosis and fractures. The effect of diabetic medications on bone disease cannot be ignored. This meta-analysis aimed to compare the effects of two types of glucose-lowering drugs, metformin and thiazolidinediones (TZD), on bone mineral density and bone metabolism in patients with diabetes mellitus.

Methods: This systematic review and meta-analysis were prospectively registered on PROSPERO, and the registration number is CRD42022320884. Embase, PubMed, and Cochrane Library databases were searched to identify clinical trials comparing the effects of metformin and thiazolidinediones on bone metabolism in patients with diabetes. The literature was screened by inclusion and exclusion criteria. Two assessors independently assessed the quality of the identified studies and extracted relevant data.

Results: Seven studies involving 1656 patients were finally included. Our results showed that the metformin group had a 2.77% (SMD = 2.77, 95%CI [2.11, 3.43]; p < 0.00001) higher bone mineral density (BMD) than the thiazolidinedione group until 52 weeks; however, between 52 and 76 weeks, the metformin group had a 0.83% (SMD = -0.83, 95%CI: [-3.56, -0.45]; p = 0.01) lower BMD. The C-terminal telopeptide of type I collagen (CTX) and procollagen type I N-terminal propeptide (PINP) were decreased by 18.46% (MD = -18.46, 95%CI: [-27.98, -8.94], p = 0.0001) and 9.94% (MD = -9.94, 95%CI: [-16.92, -2.96], p = 0.005) in the metformin group compared with the TZD group.

Keywords: bone density; bone turnover markers; diabetes; metformin; osteoporosis; thiazolidinediones.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Review

MeSH terms

  • Bone Density
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Humans
  • Metformin* / adverse effects
  • Osteoporosis* / drug therapy
  • Thiazolidinediones* / pharmacology
  • Thiazolidinediones* / therapeutic use

Substances

  • Metformin
  • Procollagen Type I
  • Thiazolidinediones

Grants and funding

This study was supported by the Natural Science Foundation of Shandong Province (No. ZR2021MH040), and Professor Shi-jie Han holds a grant from the Natural Science Foundation Committee of Shandong Province.