Generic Name

Semaglutide

Mechanism

• GLP‑1 Receptor Activation: Binds to GLP‑1 receptors on pancreatic β‑cells, stimulating glucose‑dependent insulin secretion and inhibiting glucagon release.
• Appetite Suppression: Acts on the hypothalamus to reduce appetite and delay gastric emptying, resulting in decreased caloric intake.
• Weight Reduction: The combined endocrine and gastrointestinal effects yield significant weight loss (≈5–15 % of baseline body weight).

Pharmacokinetics

• Absorption: Subcutaneous injection; ~80 % bioavailability; peak plasma concentration ∼1–3 days post‑dose.
• Distribution: Lipid‑soluble; extensive tissue penetration; ~91 % protein–bound.
• Metabolism: Non‑enzymatic, site‑specific peptide cleavage; not heavily reliant on CYP450 enzymes.
• Elimination: Primarily via proteolysis in the liver and kidneys; terminal half‑life ~6–7 weeks, enabling weekly dosing.
• Special Populations: No routine dose adjustment in mild–moderate renal or hepatic impairment.

Indications

• T2DM:
• Adults on diet/exercise or other glucose‑lowering drugs; improves HbA1c by 1.0–1.5 %.
• Obesity (≥ 30 kg/m²) or overweight (≥ 27 kg/m²) with ≥ 1 weight‑related comorbidity:
• Weight‑loss drug (once‑weekly 2.4 mg) improves weight by 12–15 %.

Contraindications

• Contraindications:
• Personal or family history of medullary thyroid carcinoma (MTC).
• Multiple endocrine neoplasia type 2 (MEN‑2).
• Warnings:
• Pancreatitis: Use with caution; monitor for abdominal pain, nausea, vomiting.
• Gallbladder disease: Increased risk of gallbladder disease/stone formation.
• Renal dysfunction: Monitor renal function; consider dose adjustment in severe CKD.

Dosing

• Route: Subcutaneous injection (arm, thigh, abdomen).
• Injection Device: Prefilled pen with single‑pen safety.
• Timing: Can be taken with or without food; consistent daily schedule recommended.

Adverse Effects

• Common:
• Nausea, vomiting, diarrhea, anorexia, transient constipation.
• Injection‑site reactions (erythema, pruritus).
• Serious:
• Acute pancreatitis (rare).
• Severe or prolonged diarrhoea → dehydration.
• Potential for obstructive jaundice or gallbladder complications.

Monitoring

• Glycemic Control: HbA1c every 3 months at a minimum.
• Weight/BMI: Baseline, then every 4–8 weeks.
• Liver Function Tests (LFTs): Baseline; monitor if symptoms develop.
• Renal Function: Scr/eGFR baseline; repeat every 6 months.
• Signs of pancreatitis/gallbladder disease: Educate patients to report persistent epigastric pain or jaundice.

Clinical Pearls

• Weight‑loss vs. glucose control: Even at the obese‑dose (2.4 mg QW), semaglutide confers modest HbA1c benefits (~0.5 %); ideal for patients needing both glycemic and weight goals.
• Smooth titration: A 4‑week interval between dose increments allows early‑phase GI side‑effects to subside and reduces discontinuation risk.
• Storage: Store at 2–8 °C; once opened, can be kept at 30‑30 °C for ≤14 days; avoid freezing.
• Drug interactions: No clinically significant CYP interactions; caution when co‑administered with potent CYP3A inducers/inhibitors due to potential changes in insulin requirements.
• Adherence aid: Use of smart‑pen technology with reminders can improve injection adherence, especially valuable in chronic therapy.

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• References – Use UpToDate, FDA prescribing information, and peer‑reviewed pharmacology texts for detailed evidence.