Generic Name

Ozempic

Mechanism

• Ozempic (semaglutide) is a *glucagon‑like peptide‑1 (GLP‑1) receptor agonist*.
• It binds to the GLP‑1 receptor on pancreatic β‑cells to stimulate insulin secretion in a glucose‑dependent manner.
• Simultaneously it suppresses glucagon release from α‑cells.
• In the gut, it slows gastric emptying and promotes satiety, reducing caloric intake.
• These combined actions lower post‑prandial glucose spikes and improve HbA1c over time.

Pharmacokinetics

• Absorption: Subcutaneous injection; peak plasma concentrations occur ~1–5 h after dosing.
• Distribution: 80–90 % protein‑bound, primarily to albumin and α‑1‑acid glycoprotein.
• Half‑life: ~5 days, allowing once‑weekly dosing.
• Metabolism: Cleaved enzymatically by proteases (including dipeptidyl peptidase‑4) and non‐specific hydrolases.
• Elimination: Renal excretion of metabolites; no active drug is excreted unchanged.
• Special populations: No dose adjustment needed for mild–moderate renal impairment; data are limited for severe impairment or liver disease.

Indications

• Type 2 diabetes mellitus (T2DM): Approved for adjunctive therapy with diet and exercise to improve glycemic control.
• Weight management: Clinical trials show significant weight loss; however, it is not yet FDA‑approved specifically for obesity.
• Cardiovascular risk reduction: 2021 ELIXA‑like data suggest reductions in major adverse cardiovascular events in patients with established cardiovascular disease.

Contraindications

• Contraindications:
• Known hypersensitivity to semaglutide or any formulation component.
• Personal or family history of medullary thyroid carcinoma (MTC).
• MEN‑2 syndrome.
• Warnings & Precautions:
• *Pancreatitis*: Reported cases; monitor abdominal pain.
• *Gallbladder disease*: Possible cholelithiasis or cholecystitis.
• *Kidney injury*: Requires monitoring of renal parameters; dose adjustment not recommended but caution advised.
• *Hypoglycemia*: Primarily when combined with insulin or sulfonylureas.
• *Allergic reactions*: Severe reactions can be life‑threatening; discontinue immediately if symptoms occur.

Dosing

• Initiation: 0.25 mg subcutaneously once weekly (Week 1) to mitigate GI upset.
• Titration:
• Week 2: 0.5 mg weekly.
• After 4 weeks: increase to 1 mg weekly if tolerated.
• Max dose: 2 mg weekly (for certain indications).
• Injection sites: Lateral thigh, abdomen, or upper arm; rotate sites to minimize lipohypertrophy.
• Missed dose: If >3 days missed, restart at 0.25 mg; do not double dose the next week.

Adverse Effects

• Common (≥10%):
• Nausea, vomiting, diarrhea, and constipation.
• Decreased appetite.
• Injection site reactions (erythema, pruritus).
• Serious (≤1%):
• Acute pancreatitis.
• Thyroid C‑cell tumors (in animal studies, not confirmed in humans).
• Acute renal injury (rare).
• Severe hypoglycemia when combined with insulin.

Monitoring

• Baseline (before initiation):
• HbA1c, fasting plasma glucose, renal function (serum creatinine, eGFR).
• Liver enzymes (AST/ALT) if chronic liver disease.
• Ongoing (every 4–12 weeks):
• HbA1c and fasting glucose.
• Weight and BMI.
• Renal and hepatic panels.
• Pulmonary function if suspected respiratory side‑effects.
• Patient education:
• Recognize signs of pancreatitis: severe upper abdominal pain radiating to shoulders.
• Important to report persistent GI, renal, or thyroid symptoms.

Clinical Pearls

• Start low, go slow: Initiating at 0.25 mg reduces GI distress and allows dose escalation with fewer side effects.
• Adjunct with basal insulin: If combining with insulin, reduce insulin dose to avoid hypoglycemia.
• Pediatric use: Not approved for children; off‑label use is unregulated and lacking safety data.
• Pregnancy & lactation: Animal data indicate embryo toxicity; human data are insufficient—use only if benefits outweigh risks.
• Weight loss synergy: Pairing Ozempic with a low‑calorie diet can produce an average 5–10 % body‑weight reduction over 1‑year.
• Cardiovascular benefit: Patients with T2DM and established CVD gain significant protection; consider as first‑line therapy in this population.
• Injection technique matters: Proper rotation prevents lipodystrophy; instruct patients on correct injection depth and angle.
• Adverse effect management: Prolonged nausea can be mitigated by taking the injection after a light meal or at bedtime.
• Screen for MTC: Periodically review personal and family thyroid history; consider thyroglobulin testing if indicated.

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• Key Takeaway: Ozempic is a potent, once‑weekly GLP‑1 receptor agonist that offers robust glycemic control, weight reduction, and cardiovascular protection with a favorable safety profile when appropriately dosed and monitored.