Impact of different anti-hyperglycaemic treatments on bone turnover markers and bone mineral density in type 2 diabetes mellitus patients: a systematic review and meta-analysis

Saadi, MSS, Das, R, Mullath Ullas, A, Powell, DE, Wilson, E and Myrtziou, I (2024) Impact of different anti-hyperglycaemic treatments on bone turnover markers and bone mineral density in type 2 diabetes mellitus patients: a systematic review and meta-analysis. International Journal of Molecular Sciences, 25 (14). ISSN 1661-6596

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Abstract

Diabetic bone disease (DBD) is a frequent complication in patients with type 2 diabetes mellitus (T2DM), characterised by altered bone mineral density (BMD) and bone turnover marker (BTMs) levels. The impact of different anti-diabetic medications on the skeleton remains unclear, and studies have reported conflicting results; thus, the need for a comprehensive systematic review is of paramount importance. A systematic search was conducted in PubMed and the Cochrane Library. The primary outcomes assessed were changes in BMD in relation to different anatomical sites and BTMs, including mainly P1NP and CTX as well as OPG, OCN, B-ALP and RANK-L. Risk of bias was evaluated using the JADAD score. The meta-analysis of 19 randomised controlled trials comprising 4914 patients showed that anti-diabetic medications overall increased BMD at the lumbar spine (SMD: 0.93, 95% CI [0.13, 1.73], p = 0.02), femoral neck (SMD: 1.10, 95% CI [0.47, 1.74], p = 0.0007) and in total hip (SMD: 0.33, 95% CI [−0.25, 0.92], p = 0.27) in comparison with placebo, but when compared with metformin, the overall effect favoured metformin over other treatments (SMD: −0.23, 95% CI [−0.39, −0.07], p = 0.004). GLP-1 receptor agonists and insulin analogues seem to improve BMD compared to placebo, while SGLT2 inhibitors and thiazolidinediones (TZDs) showed no significant effect, although studies’ number cannot lead to safe conclusions. For BTMs, TZDs significantly increased P1NP levels compared to placebo. However, no significant differences were observed for CTX, B-ALP, OCN, OPG, and RANK-L between anti-diabetic drugs and metformin or placebo. High heterogeneity and diverse follow-up durations among studies were evident, which obscures the validity of the results. This review highlights the variable effects of anti-diabetic drugs on DBD in T2DM patients, emphasising the need for long-term trials with robust designs to better understand these relationships and inform clinical decisions.

Item Type:	Article
Uncontrolled Keywords:	type 2 diabetes mellitus; anti-hyperglycaemic drugs; bone mineral density; bone turnover markers; diabetic bone disease; fracture risk; Humans; Diabetes Mellitus, Type 2; Metformin; Hypoglycemic Agents; Bone Remodeling; Bone Density; Biomarkers; anti-hyperglycaemic drugs; bone mineral density; bone turnover markers; diabetic bone disease; fracture risk; type 2 diabetes mellitus; Humans; Diabetes Mellitus, Type 2; Bone Density; Hypoglycemic Agents; Biomarkers; Bone Remodeling; Metformin; 3101 Biochemistry and Cell Biology; 31 Biological Sciences; 3404 Medicinal and Biomolecular Chemistry; 34 Chemical Sciences; 3107 Microbiology; Diabetes; 6.1 Pharmaceuticals; Metabolic and endocrine; 3 Good Health and Well Being; Humans; Diabetes Mellitus, Type 2; Bone Density; Hypoglycemic Agents; Biomarkers; Bone Remodeling; Metformin; 0399 Other Chemical Sciences; 0604 Genetics; 0699 Other Biological Sciences; Chemical Physics; 3101 Biochemistry and cell biology; 3107 Microbiology; 3404 Medicinal and biomolecular chemistry
Subjects:	R Medicine > RM Therapeutics. Pharmacology
Divisions:	Pharmacy and Biomolecular Sciences
Publisher:	MDPI AG
Date of acceptance:	17 July 2024
Date of first compliant Open Access:	9 October 2026
Date Deposited:	09 Oct 2026 14:56
Last Modified:	09 Oct 2026 14:56
DOI or ID number:	10.3390/ijms25147988
URI:	https://researchonline.ljmu.ac.uk/id/eprint/29643

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