## First-Line Agent in Type 2 Diabetes **Key Point:** Metformin is the universally recommended first-line monotherapy for type 2 diabetes mellitus in patients with normal renal function, based on its efficacy, safety profile, and cardiovascular benefits [cite:Harrison 21e Ch 417]. ### Mechanism & Advantages 1. **Mechanism of Action** - Decreases hepatic glucose production (gluconeogenesis) - Improves peripheral insulin sensitivity - Does NOT stimulate insulin secretion (hypoglycemia risk minimal) 2. **Clinical Benefits** - Weight neutral or slight weight loss - Cardiovascular risk reduction (UKPDS landmark trial) - No hypoglycemia when used alone - Cost-effective - Well-tolerated in most patients ### Contraindications & Precautions | Contraindication | Reason | |---|---| | eGFR < 30 mL/min/1.73m² | Risk of lactic acidosis | | Acute illness, sepsis, dehydration | Lactic acidosis risk | | Hepatic impairment | Increased lactate accumulation | | Acute coronary syndrome | Temporarily hold | **Clinical Pearl:** Metformin-associated lactic acidosis (MALA) is rare (~3 cases per 100,000 patient-years) when renal function is preserved and contraindications are respected. **High-Yield:** In India and globally, metformin is the standard first-line monotherapy for all newly diagnosed type 2 DM patients unless contraindicated [cite:KD Tripathi 8e Ch 24]. ### Why Metformin Over Others in This Case - **vs. Sulfonylureas (glibenclamide):** Metformin has lower hypoglycemia risk, weight-neutral profile, and proven cardiovascular benefit - **vs. Thiazolidinediones (pioglitazone):** Metformin is preferred first-line; TZDs reserved for add-on therapy or insulin resistance phenotype - **vs. DPP-4 inhibitors (vildagliptin):** Metformin has superior glucose-lowering efficacy and cost-effectiveness as monotherapy
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