Semaglutide

Semaglutide is a synthetic glucagon-like peptide-1 (GLP-1) receptor agonist with 94% structural homology to endogenous human GLP-1. GLP-1 is a peptide hormone secreted by intestinal L cells in response to food intake; it stimulates glucose-dependent insulin secretion, suppresses glucagon release, slows gastric emptying, and acts on GLP-1 receptors in the hypothalamus and brainstem to reduce appetite and caloric intake. Semaglutide binds to and activates the GLP-1 receptor with greater potency and a substantially longer duration of action than native GLP-1 — an elimination half-life of approximately 7 days, enabling once-weekly subcutaneous injection or once-daily oral dosing.¹²

Semaglutide is manufactured by Novo Nordisk and sold under three brand names targeting distinct indications: Ozempic (subcutaneous injection, type 2 diabetes); Rybelsus (oral tablet, type 2 diabetes); and Wegovy (subcutaneous injection at higher maintenance doses, chronic weight management and cardiovascular risk reduction). As of March 2026, oral Wegovy tablets were also FDA-approved, making semaglutide the first oral agent in its class with a weight management indication.¹

Ozempic (semaglutide injection, 0.5 mg, 1 mg, 2 mg):

• Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
• Reduction of the risk of major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke) in adults with type 2 diabetes and established cardiovascular disease.²

Wegovy (semaglutide injection, 2.4 mg maintenance dose):

• Chronic weight management in adults with an initial BMI of ≥30 kg/m² (obesity), or ≥27 kg/m² (overweight) with at least one weight-related comorbid condition, as an adjunct to a reduced-calorie diet and increased physical activity.¹
• Reduction of the risk of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke in adults with established cardiovascular disease and obesity or overweight.¹

Off-label use: Ozempic is frequently prescribed off-label for weight loss in individuals without type 2 diabetes; this use is pharmacologically rational given the overlapping mechanism but falls outside the approved Ozempic indication. Wegovy is the approved product for this purpose.

All semaglutide injections use a structured dose-escalation schedule to reduce gastrointestinal side effects.¹²

Ozempic starts at 0.25 mg once weekly for 4 weeks, then increases to 0.5 mg once weekly; dose may be further increased to 1 mg or 2 mg weekly based on response.

Wegovy starts at 0.25 mg once weekly and escalates through 0.5 mg, 1 mg, 1.7 mg, to a maintenance dose of 2.4 mg once weekly over approximately 16–20 weeks. Dose escalation may be slowed if gastrointestinal side effects occur.

All semaglutide injections are administered subcutaneously in the abdomen, thigh, or upper arm. Injection site should be rotated with each dose.

Real-world practice: The 4-week escalation schedule in the FDA label is a minimum — many prescribers extend each step to 6–8 weeks if gastrointestinal side effects are significant. There is no clinical evidence that rushing the escalation improves outcomes, and tolerability is substantially better with a slower titration. Discuss your pace with your prescribing physician.

Subcutaneous injection (Ozempic and Wegovy); oral tablet (Rybelsus, oral Wegovy). Oral semaglutide must be taken on an empty stomach with no more than 4 ounces of water, at least 30 minutes before any food, beverage, or other oral medication.

Unopened pens: refrigerate at 36°F to 46°F (2°C to 8°C); do not freeze. After first use: may be stored at room temperature below 86°F (30°C) or refrigerated; use within 56 days. Keep away from direct heat and light. Remove pen cap only when administering the dose.¹

Boxed warning: GLP-1 receptor agonists including semaglutide cause dose-dependent and duration-dependent thyroid C-cell tumors in rodents. It is unknown whether semaglutide causes thyroid C-cell tumors in humans. Semaglutide is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).¹

Key warnings and considerations from the FDA label:¹²

• Pancreatitis: Cases of acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis, have been reported. Discontinue if pancreatitis is suspected; do not restart if confirmed.
• Gastrointestinal effects: Nausea, vomiting, diarrhea, constipation, and abdominal pain are the most common adverse effects and are typically most pronounced during the dose-escalation phase. GI events are the most frequent reason for discontinuation.
• Hypoglycemia: Semaglutide alone carries a low risk of hypoglycemia; risk increases substantially when combined with a sulfonylurea or insulin. Dose reduction of the concomitant agent may be needed.
• Diabetic retinopathy: Rapid improvement in glycemic control has been associated with a temporary worsening of diabetic retinopathy; patients with pre-existing retinopathy should be monitored.
• Heart rate increase: Mean increases in resting heart rate of 1–6 beats per minute have been observed; use with caution in patients with pre-existing tachycardia.
• Oral contraceptives: Semaglutide slows gastric emptying and may impair absorption of co-administered oral medications. Females using oral contraceptives may need to switch to a non-oral method or add a barrier method during dose escalation.
• Pregnancy and lactation: May cause fetal harm based on animal data. Discontinue at least 2 months before a planned pregnancy due to the long washout period. Not recommended during breastfeeding.¹