Repurposing Drugs for Diabetes Mellitus as Potential Pharmacological Treatments for Sarcopenia - A Narrative Review

Abstract

Sarcopenia, the age-related loss of muscle strength and mass or quality, is a common condition with major adverse consequences. Although the pathophysiology is incompletely understood, there are common mechanisms between sarcopenia and the phenomenon of accelerated ageing seen in diabetes mellitus. Drugs currently used to treat type 2 diabetes mellitus may have mechanisms of action that are relevant to the prevention and treatment of sarcopenia, for those with type 2 diabetes and those without diabetes. This review summarises shared pathophysiology between sarcopenia and diabetes mellitus, including the effects of advanced glycation end products, mitochondrial dysfunction, chronic inflammation and changes to the insulin signalling pathway. Cellular and animal models have generated intriguing, albeit mixed, evidence that supports possible beneficial effects on skeletal muscle function for some classes of drugs used to treat diabetes, including metformin and SGLT2 inhibitors. Most human observational and intervention evidence for the effects of these drugs has been derived from populations with type 2 diabetes mellitus, and there is a need for intervention studies for older people with, and at risk of, sarcopenia to further investigate the balance of benefit and risk in these target populations. Not all diabetes treatments will be safe to use in those without diabetes because of variable side effects across classes. However, some agents [including glucagon-like peptide (GLP)-1 receptor agonists and SGLT2 inhibitors] have already demonstrated benefits in populations without diabetes, and it is these agents, along with metformin, that hold out the most promise for further investigation in sarcopenia.

Fig. 1

Mechanisms potentially contributing to sarcopenia that may be amenable to modification with drugs used to treat diabetes