Type 2 Diabetes
A chronic metabolic disease characterised by elevated blood glucose from insulin resistance and declining insulin production. It is the primary approved indication for most GLP-1 receptor agonists. Semaglutide, liraglutide, dulaglutide, exenatide, lixisenatide, and tirzepatide are all approved for type 2 diabetes.
Technical Context
T2D pathophysiology (DeFronzo's ominous octet): insulin resistance in muscle, liver, and adipose tissue; beta cell failure (progressive decline in insulin secretion); increased hepatic glucose output; decreased incretin effect; increased glucagon secretion; enhanced renal glucose reabsorption; neurotransmitter dysfunction (appetite dysregulation); and systemic inflammation. Treatment algorithm (ADA/EASD 2022): first-line metformin + lifestyle; second-line selection based on comorbidities — GLP-1 RA preferred for patients with established cardiovascular disease (ASCVD) or at high cardiovascular risk (based on CVOT data), patients with heart failure, and patients where weight management is a priority. Semaglutide, liraglutide, dulaglutide, exenatide, lixisenatide, and tirzepatide are all approved for T2D. The GLP-1 RA class has advanced from fourth-line agents to preferred second-line therapy over the past decade based on accumulating cardiovascular outcome and weight management evidence.