Update on: effects of anti-diabetic drugs on bone metabolism

ABSTRACT

Introduction

Preclinical, clinical, and population-based studies have provided evidence that anti-diabetic drugs affect bone metabolism and may affect the risk of fracture in diabetic patients.

Areas covered

An overview of the skeletal effects of anti-diabetic drugs used in type 2 diabetes is provided. Searches on AdisInsight, PubMed, and Medline databases were conducted up to 1^st July 2020. The latest evidence from randomized clinical trials and population-based studies on the skeletal safety of the most recent drugs (DPP-4i, GLP-1RA, and SGLT-2i) is provided.

Expert opinion

Diabetic patients present with a higher risk of fracture for a given bone mineral density suggesting a role of bone quality in the etiology of diabetic fracture. Bone quality is difficult to assess in human clinical practice and the use of preclinical models provides valuable information on diabetic bone alterations. As several links have been established between bone and energy homeostasis, it is interesting to study the safety of anti-diabetic drugs on the skeleton. So far, evidence for the newest molecules suggests a neutral fracture risk, but further studies, especially in different types of patient populations (patients at risk or with history of cardiovascular disease, renal impairment, neuropathy) are required to fully appreciate this matter.

KEYWORDS:

• Bone
• anti-diabetic drug
• fracture risk
• GLP-1RA
• SGLT2i
• DPP-4i

Article highlights

• Patients suffering with type 1 and type 2 diabetes mellitus are at high risk of bone fracture and anti-diabetic drugs may interfere with skeletal physiology.

• Metformin has been associated in vitro with beneficial effects on bone health, but in vivo demonstration of this effect is lacking.

• Thiazolidinediones have a negative impact on bone by promoting adipogenesis at the expense of osteoblastogenesis. However, early data from new selective PPARγ modulators suggest that adverse effects on bone are no longer an issue.

• Sulfonylureas, and related meglitinides, are often considered as a control group in the assessment of bone effect of new oral anti-diabetic agent but data are scarce to ensure that these oral agents do not alter bone physiology.

• GLP-1 receptor agonists and DPP-4 inhibitors do not seem to reduce the risk of fracture in clinical trials, despite promising effects in vitro and in preclinical studies.

• Early reports with SGLT2 inhibitors suggested higher fracture risk but recent evidences support a neutral effect on this parameter.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.