Effects of sodium-glucose cotransporter 2 inhibitors on bone metabolism in patients with type 2 diabetes mellitus: a systematic review and meta-analysis

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Effects of sodium-glucose cotransporter 2 inhibitors on bone metabolism in patients with type 2 diabetes mellitus: a systematic review and meta-analysis

Wang et al., 2024 | BMC Endocr Disord | Meta Analysis

Citation

Wang Jing, Li Xin, ... Lei Chen. Effects of sodium-glucose cotransporter 2 inhibitors on bone metabolism in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. BMC Endocr Disord. 2024-Apr-24;24(1):52. doi:10.1186/s12902-024-01575-8

Abstract

BACKGROUND: Sodium glucose cotransporter 2 (SGLT2) inhibitors are widely used in type 2 diabetes mellitus (T2DM) therapy. The impact of SGLT2 inhibitors on bone metabolism has been widely taken into consideration. But there are controversial results in the study on the effect of SGLT2 inhibitors on bone metabolism in patients with T2DM. Therefore, we aimed to examine whether and to what extent SGLT2 inhibitors affect bone metabolism in patients with T2DM. METHODS: A literature search of randomized controlled trials (RCTs) was conducted through PubMed, Web of Science, Embase, Cochrane databases, and Scopus from inception until 15 April 2023. Eligible RCTs compared the effects of SGLT2 inhibitors versus placebo on bone mineral density and bone metabolism in patients with T2DM. To evaluate the differences between groups, a meta-analysis was conducted using the random effects inverse-variance model by utilizing standardized mean differences (SMD). RESULTS: Through screening, 25 articles were finally included, covering 22,828 patients. The results showed that, compared with placebo, SGLT2 inhibitors significantly increased parathyroid hormone (PTH, SMD = 0.13; 95%CI: 0.06, 0.20), and cross-linked C-terminal telopeptides of type I collagen (CTX, SMD = 0.11; 95%CI: 0.01, 0.21) in patients with T2DM, decreased serum alkaline phosphatase levels (ALP, SMD = -0.06; 95%CI: -0.10, -0.03), and had no significant effect on bone mineral density (BMD), procollagen type 1 N-terminal propeptide (P1NP), 25-hydroxy vitamin D, tartrate resistant acid phosphatase-5b (TRACP-5b) and osteocalcin. CONCLUSIONS: SGLT2 inhibitors may negatively affect bone metabolism by increasing serum PTH, CTX, and decreasing serum ALP. This conclusion needs to be verified by more studies due to the limited number and quality of included studies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, identifier CRD42023410701.

Key Findings

Through screening, 25 articles were finally included, covering 22,828 patients. The results showed that, compared with placebo, SGLT2 inhibitors significantly increased parathyroid hormone (PTH, SMD = 0.13; 95%CI: 0.06, 0.20), and cross-linked C-terminal telopeptides of type I collagen (CTX, SMD = 0.11; 95%CI: 0.01, 0.21) in patients with T2DM, decreased serum alkaline phosphatase levels (ALP, SMD = -0.06; 95%CI: -0.10, -0.03), and had no significant effect on bone mineral density (BMD), procoll

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population t2dm
Sample Size 22828
Age Range See abstract
Condition diabetes

MeSH Terms

  • Humans
  • Sodium-Glucose Transporter 2 Inhibitors
  • Diabetes Mellitus, Type 2
  • Bone Density
  • Bone and Bones
  • Randomized Controlled Trials as Topic

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Systematic Review, Meta-Analysis
  • Vertical: collagen

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09