Semaglutide
Brand names: Ozempic (injectable), Wegovy (weight), Rybelsus (oral)
Class: 🩸 Antidiabetics
What examiners watch for is recognition that semaglutide is now three drugs in one — Ozempic for T2DM, Wegovy for weight management, and Rybelsus as the oral form. It is a GLP-1 receptor agonist that increases glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying, and reduces appetite. Cardiovascular outcome trials (SUSTAIN-6) showed reduced MACE in T2DM with established ASCVD or high CV risk. Wegovy is FDA-approved for chronic weight management at BMI ≥30 (or ≥27 with a weight-related comorbidity). The trade-offs are GI (nausea, vomiting, constipation), pancreatitis warnings, and a black box for medullary thyroid cancer (avoid in MEN2 and personal/family history). Titrate slowly to limit nausea.
✅ Indications
T2DM, chronic weight management (Wegovy = BMI ≥30 or ≥27 with comorbidity), CV risk reduction in T2DM + ASCVD.
⚙️ Mechanism of Action
GLP-1 receptor agonist — ↑ insulin secretion, ↓ glucagon, slows gastric emptying.
📏 Dosing
Ozempic: 0.25 mg SC weekly → 0.5–2 mg. Rybelsus PO: 3→7→14 mg daily.
🚫 Contraindications
Personal/family history medullary thyroid cancer, MEN-2, pregnancy (weight indication).
⚠️ Adverse Effects
🤢 N/V/D (often limits dose escalation), pancreatitis, gastroparesis, gallbladder disease. Black-box warning for thyroid C-cell tumors (animal data).
🔬 Monitoring
BG, A1c, weight; renal function; monitor for signs of pancreatitis.
💎 Board Pearls
- 📉 Average 10–15% weight loss — game changer for obesity + diabetes.
- 🤢 Start LOW, escalate slowly — GI side effects are dose-dependent and the main reason for discontinuation.
- ⏸️ HOLD before elective surgery (gastroparesis → aspiration risk).
- 🚫 NEVER with DPP-4 inhibitors (sitagliptin) — redundant mechanism.
Practice Questions
A 54-year-old woman with type 2 diabetes is on semaglutide (Ozempic) 1 mg subcutaneously once weekly. She is scheduled for elective laparoscopic cholecystectomy in 10 days and calls the clinic to ask about her injection, which is due tomorrow. Chart review shows her last dose was 6 days ago. Which pre-operative instruction is MOST appropriate?
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- Insulin Glargine — Lantus, Basaglar, Toujeo
- Insulin Lispro — Humalog
Sources
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