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Semaglutide (Ozempic® Injection)
Semaglutide, marketed as Ozempic®, is a glucagon-like peptide-1 (GLP-1) receptor agonist administered via subcutaneous injection. It is used to manage type 2 diabetes mellitus (T2DM) and has demonstrated cardiovascular benefits. This article details its pharmacology, clinical applications, and safety profile, referencing the British National Formulary (BNF), Lippincott Textbook of Pharmacology, and Lange Basic & Clinical Pharmacology.
Semaglutide mimics endogenous GLP-1, enhancing glucose-dependent insulin secretion from pancreatic β-cells and suppressing glucagon release from α-cells (Lippincott). Key effects include:
- Slowed Gastric Emptying: Reduces postprandial glucose spikes.
- Appetite Suppression: Activates brain receptors to promote satiety, aiding weight loss (Lange).
- Cardiovascular Protection: Shown in trials (e.g., SUSTAIN-6) to reduce major adverse cardiovascular events (MACE) in high-risk patients (BNF).
- Type 2 Diabetes Mellitus: Adjunctive to diet/exercise ± other antidiabetic agents (e.g., metformin, insulin).
- Cardiovascular Risk Reduction: For patients with T2DM and established cardiovascular disease.
- Weight Management: Off-label use due to significant weight loss effects (approved in higher doses as Wegovy®) (BNF).
- Administration: Subcutaneous injection (abdomen, thigh, or upper arm) once weekly.
- Titration:
- Initial: 0.25 mg weekly for 4 weeks (to minimize GI side effects).
- Maintenance: Increase to 0.5 mg or 1 mg weekly based on glycemic response.
- Renal/Hepatic Impairment: No dose adjustment needed for mild-to-moderate impairment. Use caution in severe renal impairment (eGFR <30 mL/min/1.73m²) (BNF).
- Gastrointestinal: Nausea (15–20%), vomiting, diarrhea, constipation.
- Mild hypoglycemia (with concurrent insulin/sulfonylureas).
Serious:
- Pancreatitis: Monitor for severe abdominal pain.
- Diabetic Retinopathy Complications: Risk in patients with pre-existing retinopathy.
- Thyroid C-Cell Tumors: Contraindicated in personal/family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (Lippincott).
- Acute Kidney Injury: Dehydration-related, especially with nausea/vomiting (Lange).
- Contraindications:
- Personal/family history of MTC.
- Pregnancy (Category C: animal studies show fetal risk; avoid unless benefits outweigh risks).
- HbA1c, renal function, and signs of pancreatitis.
- Educate patients on hypoglycemia symptoms if used with insulin/sulfonylureas.
Discontinue if pregnancy occurs; avoid during breastfeeding (BNF).
- Insulin/Sulfonylureas: Increased hypoglycemia risk; consider dose reduction.
- Oral Medications: Delayed absorption of drugs dependent on rapid GI uptake (e.g., antibiotics, oral contraceptives—take 1 hour before semaglutide).
- Diuretics/NSAIDs: May exacerbate dehydration or renal impairment (Lange).
- Generic: Semaglutide.
- Brand Name: Ozempic® (injection); Wegovy® (higher dose for obesity).
