Diabetes drugs — insulin & orals

◆Metformin (first-line for T2DM)

• •Mechanism: ↓ hepatic gluconeogenesis; ↑ peripheral insulin sensitivity
• •Side effects: GI upset (titrate slowly), B12 deficiency (check yearly), LACTIC ACIDOSIS
• •Contraindications: eGFR <30 (caution 30–45); hold for contrast, surgery, acute illness
• •Does NOT cause hypoglycemia by itself; weight neutral or modest loss

◆GLP-1 agonists (semaglutide, liraglutide, dulaglutide, tirzepatide)

• •Mechanism: ↑ glucose-dependent insulin secretion, ↓ glucagon, slows gastric emptying, ↑ satiety
• •Big wins: weight loss, ↓ CV mortality (semaglutide, liraglutide), renal protection
• •Side effects: nausea/vomiting, pancreatitis, gallstones
• •BLACK BOX: medullary thyroid cancer (avoid in MEN-2, personal/family hx of MTC)

◆SGLT-2 inhibitors (-flozin: empagliflozin, dapagliflozin, canagliflozin)

• •Mechanism: ↓ glucose reabsorption in PCT → glucosuria
• •Big wins: ↓ CV mortality, ↓ HF hospitalizations, ↓ progression of CKD (independent of glycemic effect)
• •Side effects: euglycemic DKA, mycotic GU infections, volume depletion, Fournier gangrene (rare)
• •Hold for surgery, illness, fasting; restart when eating normally
• •Now first-line add-on for T2DM + HFrEF or CKD

◆Other orals

• •Sulfonylureas (glipizide, glyburide): ↑ insulin release → HYPOGLYCEMIA (esp glyburide in elderly); weight gain
• •DPP-4 inhibitors (-gliptin: sitagliptin): mild A1c lowering, weight neutral; pancreatitis risk (small), arthralgia
• •TZDs (pioglitazone): insulin sensitizer; CONTRAINDICATED in CHF (fluid retention), bladder cancer (controversial), fractures
• •α-glucosidase inhibitors (acarbose): GI side effects, mild A1c effect (less used)

◆Insulin

• •Rapid (lispro, aspart, glulisine): onset 15 min, peak 1 hr, duration 3–5 hr — with meals
• •Short (regular): onset 30 min, peak 2 hr, duration 6–8 hr — IV in DKA
• •Intermediate (NPH): onset 1–2 hr, peak 6–10 hr — basal in cheaper regimens
• •Long (glargine, detemir, degludec): peakless, 18–24+ hr — true basal
• •Total daily dose start: 0.4–0.5 units/kg, split 50% basal / 50% prandial
• •Insulin requirement DOUBLES in DKA recovery; HALVES during illness or fasting

Diabetes drug picker by comorbidity