Ozempic - Drug Monograph

Introduction

Ozempic (semaglutide) is a glucagon-like peptide-1 (GLP-1) receptor agonist manufactured by Novo Nordisk. It is administered via subcutaneous injection and is primarily indicated for the management of type 2 diabetes mellitus. Recently, it has gained significant attention for its weight management benefits when used at higher doses (marketed separately as Wegovy).

Mechanism of Action

Semaglutide is a GLP-1 analog that activates GLP-1 receptors, leading to:

• Glucose-dependent stimulation of insulin secretion
• Suppression of glucagon secretion
• Slowing of gastric emptying
• Promotion of satiety and reduced food intake through central nervous system effects

These mechanisms work synergistically to improve glycemic control and promote weight loss.

Indications

• FDA-approved:

- As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus - To reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease

• Off-label uses (not FDA-approved for these indications):

- Weight management (higher dose formulation approved as Wegovy) - Polycystic ovary syndrome (PCOS) - Non-alcoholic steatohepatitis (NASH)

Dosage and Administration

• Administer subcutaneously in abdomen, thigh, or upper arm
• May be given without regard to meals
• Rotate injection sites
• If a dose is missed, administer within 5 days; otherwise, skip and resume regular schedule

• Renal impairment: No dose adjustment needed
• Hepatic impairment: No dose adjustment needed
• Elderly: No dose adjustment needed
• Pediatrics: Safety and effectiveness not established

Pharmacokinetics

• Absorption: Bioavailability ~89%; Tmax: 1-3 days post-dose
• Distribution: Volume of distribution ~12.5 L; >99% plasma protein bound
• Metabolism: Proteolytic cleavage and beta-oxidation of fatty acid side chain
• Elimination: Half-life ~1 week; primarily renal elimination (3% unchanged)
• Steady-state: Achieved after 4-5 weeks of dosing

Contraindications

• Personal or family history of medullary thyroid carcinoma
• Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
• Hypersensitivity to semaglutide or any product components
• Pregnancy (based on animal data showing fetal harm)

Warnings and Precautions

• Pancreatitis: Discontinue if suspected
• Diabetic retinopathy: Monitor in patients with history
• Hypoglycemia: Increased risk when used with insulin or sulfonylureas
• Acute kidney injury: Monitor renal function
• Acute gallbladder disease: Monitor for symptoms
• Suicidal ideation: Monitor for depression or suicidal thoughts

Drug Interactions

• Insulin and insulin secretagogues: Increased risk of hypoglycemia (dose reduction may be needed)
• Oral medications: May delay gastric emptying and affect absorption (administer concomitantly or monitor effects)
• Warfarin: Monitor INR (potential interaction)
• Cyclosporine: Increased cyclosporine exposure possible

Adverse Effects

• Nausea (20%)
• Diarrhea (9%)
• Vomiting (5%)
• Constipation (5%)
• Abdominal pain (7%)
• Injection site reactions (5%)

• Pancreatitis (0.3%)
• Acute kidney injury
• Severe hypersensitivity reactions
• Diabetic retinopathy complications
• Gallbladder disease
• Suicidal behavior and ideation

Monitoring Parameters

• Glycemic control: HbA1c every 3 months until stable
• Renal function: Serum creatinine at baseline and periodically
• Pancreatitis symptoms: Abdominal pain, nausea, vomiting
• Thyroid nodules: Neck examination; calcitonin monitoring if indicated
• Weight: Regular monitoring
• Cardiovascular status: Blood pressure, heart rate
• Vision: Annual diabetic eye exams

Patient Education

• Administration: Proper injection technique, site rotation, storage
• Timing: Once weekly dosing, same day each week
• Gastrointestinal effects: Usually transient; gradual dose escalation helps minimize
• Hypoglycemia: Recognition and management, especially with concomitant therapies
• Warning signs: Symptoms requiring immediate medical attention (severe abdominal pain, allergic reactions)
• Pregnancy planning: Discuss with provider before conception
• Adherence: Importance of consistent dosing
• Lifestyle: Continued importance of diet and exercise

References

1. FDA Prescribing Information: Ozempic (semaglutide) injection. Revised 2023. 2. Marso SP, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016;375(19):1834-1844. 3. Aroda VR, et al. Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin in patients with type 2 diabetes. Lancet Diabetes Endocrinol. 2017;5(5):355-366. 4. Davies M, et al. Semaglutide 2.4 mg once a week in adults with overweight or obesity. N Engl J Med. 2021;384(11):989-1002. 5. American Diabetes Association. Standards of Medical Care in Diabetes—2023. Diabetes Care. 2023;46(Suppl 1):S1-S291. 6. Product Monograph: Ozempic. Novo Nordisk Canada Inc. 2023. 7. ClinicalTrials.gov: Various semaglutide trials (NCT01720446, NCT03086330, NCT03574597).