Semaglutida

Semaglutide mimics endogenous GLP-1, an incretin hormone secreted by intestinal L-cells. Its molecular effects include:

• Glucose-dependent insulin secretion stimulation (beta cells)
• Glucagon secretion suppression (alpha cells)
• Delayed gastric emptying, reducing postprandial glucose absorption
• Appetite reduction through hypothalamic and solitary tract nucleus signaling

• Type 2 diabetes: Glycemic control as mono or combination therapy
• Obesity/overweight: Body weight reduction (BMI ≥30 or ≥27 with comorbidities)
• Cardiovascular risk reduction in T2D patients with established CVD
• MASLD/metabolic steatohepatitis: Under active investigation

Beneficial effects: HbA1c reduction of 1.5–2%, weight loss of 10–15% (2.4 mg/week dose), 26% reduction in MACE (SUSTAIN-6 / FLOW).

Adverse effects:

• Gastrointestinal (very common): nausea, vomiting, diarrhea, especially at initiation
• Cholelithiasis and cholecystitis
• Acute pancreatitis (rare)
• Hypoglycemia when combined with sulfonylureas or insulin

• Contraindicated in personal or family history of medullary thyroid carcinoma or MEN type 2
• Do not use during pregnancy or breastfeeding; discontinue 2 months before planned conception
• Caution in severe gastroparesis
• Not recommended in severe renal/hepatic impairment (limited data)

FDA approved: Ozempic® (sc, 0.5/1/2 mg/week, T2D, 2017), Wegovy® (sc, 2.4 mg/week, obesity, 2021), Rybelsus® (oral, 7/14 mg/day, T2D, 2019). EMA approved with equivalent indications.

T2D: start 0.25 mg/week × 4 weeks → 0.5 mg → 1 mg → 2 mg (max). Obesity: progressive titration up to 2.4 mg/week.

Prefilled pens: 2–8°C. Once opened, ≤30°C up to 8 weeks. Rybelsus: room temperature (<30°C).