Antidiabetics
What examiners watch for is whether you can move past metformin and pick a second agent based on the patient's strongest comorbidity. Metformin remains first-line for type 2 diabetes — it lowers hepatic gluconeogenesis, is weight-neutral, and carries the lowest hypoglycemia risk. The decision tree from there is the high-yield content: GLP-1 agonists (semaglutide, liraglutide) for established ASCVD or obesity; SGLT2 inhibitors (empagliflozin, dapagliflozin) for heart failure or CKD with proteinuria; sulfonylureas and basal insulin when cost or A1C demands fast lowering. Memorize the side-effect signatures: GI for metformin, hypoglycemia for sulfonylureas, GU infections and DKA risk for SGLT2s, pancreatitis warnings for GLP-1s.
📖 Overview
Type 2 diabetes management starts with lifestyle + metformin. Add a GLP-1 receptor agonist (semaglutide) or SGLT2 inhibitor (empagliflozin) early for patients with ASCVD, CKD, or HF — both classes have proven cardiovascular and renal benefits independent of A1c. Sulfonylureas (glipizide) and DPP-4 inhibitors are older options. Insulin is added when oral/injectable agents fail or for T1DM.
⚙️ Mechanism of Action
Metformin ↓ hepatic gluconeogenesis; GLP-1 agonists ↑ insulin secretion, ↓ glucagon, slow gastric emptying; SGLT2 inhibitors block renal glucose reabsorption; sulfonylureas stimulate pancreatic insulin release; insulin replaces endogenous production.
💎 Board Pearls
- 🫀 GLP-1 and SGLT2i have proven CV/renal benefit — use early in high-risk patients.
- ⚠️ Metformin: HOLD if eGFR <30, contrast imaging, sepsis (risk of lactic acidosis).
- 🍎 Metformin → B12 deficiency after long-term use (check annually).
- ⚡ Sulfonylureas (glipizide) → HYPOGLYCEMIA is the #1 adverse effect; avoid in elderly.
- 🍯 SGLT2 → euglycemic DKA (BG can be <250 despite ketosis), genital mycotic infections.
- 🤢 GLP-1 → N/V most common, pancreatitis warning, gastroparesis.
- 💉 A1c goal: <7% most adults, <7.5–8% older/frail/shorter life expectancy.
💊 Drugs in This Class
- Metformin — Glucophage, Fortamet, GlumetzaFirst-line for type 2 diabetes, prediabetes, PCOS (off-label), weight maintenance in diabetes.
- Glipizide — GlucotrolType 2 diabetes adjunct when metformin insufficient.
- Empagliflozin — JardianceT2DM, HFrEF, HFpEF, CKD (slows progression). All adults regardless of A1c.
- Semaglutide — Ozempic (injectable), Wegovy (weight), Rybelsus (oral)T2DM, chronic weight management (Wegovy = BMI ≥30 or ≥27 with comorbidity), CV risk reduction in T2DM + ASCVD.
- Insulin Glargine — Lantus, Basaglar, ToujeoBasal insulin for T1DM and T2DM requiring insulin.
- Insulin Lispro — HumalogMealtime (bolus) insulin, insulin pump therapy, DKA/HHS (IV).
Practice Questions
A 58-year-old man with type 2 diabetes, a 3-year history of heart failure with reduced ejection fraction (EF 35%), and an A1C of 8.2% on metformin 1000 mg BID presents for routine follow-up. His eGFR is 58 mL/min/1.73 m². Per current ADA 2025 standards, which of the following is the most appropriate next step in diabetes management?
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