COMPARATIVE STUDY OF NEWER ANTIDIABETIC AGENTS ON INSULIN RESISTANCE

Subhrajeet Dash*, Sonali Behera, Sushil Kumar Sahoo, Subhasmita Das, Nancy Mohapatra, Samrat Dutta and Chinmay Kumar Pradhan

Insulin resistance is a key metabolic abnormality that significantly contributes to the onset and progression of type 2 diabetes mellitus (T2DM). Over the past decade, several novel antidiabetic agents have emerged, offering targeted approaches to improve glycemic control and address underlying metabolic dysfunction. This paper presents a comparative evaluation of newer therapeutic classes—including GLP-1 receptor agonists, SGLT-2 inhibitors, dual GLP-1/GIP receptor agonists, thiazolidinediones, and mitochondrial pyruvate carrier inhibitors—with respect to their effects on insulin sensitivity. Evidence was synthesized from recent clinical trials, systematic reviews, and meta-analyses. All these agents demonstrate the potential to enhance insulin responsiveness, albeit via distinct mechanisms. GLP-1 receptor agonists and dual agonists primarily improve insulin resistance through weight reduction and metabolic regulation. SGLT-2 inhibitors facilitate glucose excretion, thereby indirectly lowering insulin resistance. Thiazolidinediones act directly on insulin-sensitive tissues but are limited by adverse effect profiles. Mitochondrial pyruvate carrier inhibitors represent an emerging therapeutic avenue with both metabolic and anti-inflammatory benefits. The findings suggest that combination regimens targeting complementary mechanisms may provide optimal outcomes for patients with T2DM.