The Role of Sodium-Glucose Cotransporter 2 Inhibitors on Peripheral Nerves and Skeletal Muscle Function in Type 2...

Diabetes is one of the four main non-communicable diseases in Sri Lanka with prevalence of 26%. SGLT2 inhibitors, primarily used for glycaemic control in type 2 diabetes, have recently garnered attention for their potential effects on neuromuscular function. The primary objective of this scoping review was to map the existing literature to determine the extent, range and nature of published evidence on the effects of SGLT2 inhibitors on peripheral nerve morphology, electrophysiology and skeletal muscle function and metabolic kinetics.

Guided by the PRISMA extension for Scoping Reviews (PRISMA-ScR), an electronic search was executed across PubMed, ScienceDirect and Google Scholar for literature published from 2010 onwards. Applying a strict Population-Concept-Context (PCC) framework, two independent reviewers screened and analyzed studies evaluating human populations or corresponding animal models with T2DM (Population) undergoing SGLT2 inhibitor therapy (Concept), in relation to somatic/autonomic nerve conduction, nerve histology, muscle mass and metabolic processing (Context). Data extraction charted study characteristics, species, specific drug types, duration of effect and symptom relief versus electrophysiological outcomes.

Thirty-two studies met the inclusion criteria with 16 evaluating peripheral nerves and 16 focusing on skeletal muscle kinetics. Evidence from animal models and human trials suggests potential improvements in peripheral nerve conduction velocity (NCV), epidermal nerve fiber density, skeletal muscle substrate flexibility, toward fatty acid and ketone oxidation, and mitochondrial structural dynamics. However, divergent and neutral functional outcomes, particularly in human muscle grip strength and short-term versus long-term clinical symptom recovery-were observed, highlighting critical knowledge gaps.

SGLT2 inhibitors demonstrate promising neuroprotective and myo-metabolic modulating properties via multiple pathways. However, the current literature is heavily geared towards animal models, with clear knowledge gaps on long-term effects on human function and symptom improvement. This review provides a mapped baseline to guide future targeted clinical trials.