What causes insulin resistance?
Insulin resistance is driven by a converging set of factors: excess visceral adiposity, chronic caloric surplus, low muscle mass, poor sleep, chronic inflammation, genetic predisposition, and certain medications. It develops over years and is reversible early in its course.
Full answer
Insulin resistance is the progressive loss of cellular responsiveness to insulin, forcing the pancreas to secrete more insulin to maintain normal glucose. It is multifactorial. The dominant drivers are excess visceral adiposity (which secretes inflammatory cytokines and free fatty acids), chronic caloric surplus paired with low physical activity, low skeletal-muscle mass (which reduces the body's largest glucose sink), poor sleep, chronic systemic inflammation, and genetic predisposition. Certain medications — long-term glucocorticoids, some atypical antipsychotics — also contribute. The trajectory plays out over years: fasting insulin and HOMA-IR rise first, then post-prandial glucose, then fasting glucose and A1c. Early in the course it is reversible with body composition, resistance training, and — where indicated — provider-reviewed GLP-1 therapy.
Educational. Not a substitute for individualized provider review.
- Metabolic Syndrome — Primary source · oMeds
- Metabolic intelligence — Reference · oMeds Learn
- Reviewed by Dr. Laura Purdy, MD, MBA · Clinical Director, oMeds · Last reviewed 2026-05-29