Redox Homeostasis in Metabolic Syndrome and Type II Diabetes: Role of Skeletal Muscle and Impact of Gold-Standard Treatments

Metabolic syndrome and type II diabetes pose a significant international health burden, with the latter characterized by insulin resistance. Patients must rely on therapies that maintain glucose homeostasis when endogenous systems become dysfunctional. Skeletal muscle, as the largest insulin-sensitive tissue in the body, plays a critical role in maintaining glucose homeostasis. During disease progression, chronic nutrient overload shifts redox balance to a pro-oxidant state, further exacerbating metabolic dysfunction. First-line treatments, such as metformin and insulin, along with newly adopted incretin-based therapies, modulate the redox state of skeletal muscle. This review explores how the redox state of healthy skeletal muscle is altered throughout metabolic disease progression and how these changes contribute to a worsening phenotype. We also highlight how each class of regularly prescribed medications targets redox-sensitive systems in skeletal muscle, identifying literature gaps and areas for future investigation.