WEGOVY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for WEGOVY (WEGOVY).
Semaglutide, a GLP-1 receptor agonist, increases insulin secretion, decreases glucagon secretion, delays gastric emptying, and reduces appetite via central GLP-1 receptor activation.
| Metabolism | Primarily metabolized via proteolytic cleavage of the peptide backbone, not by CYP450 enzymes. Minor involvement of neutral endopeptidase (NEP). |
| Excretion | Primarily renal; approximately 97% of the dose is excreted unchanged in urine, with less than 3% in feces via biliary excretion. |
| Half-life | Terminal elimination half-life is approximately 1 week (6–8 days), supporting once-weekly subcutaneous dosing. |
| Protein binding | Approximately 99% bound to albumin. |
| Volume of Distribution | Approximately 0.2 L/kg, indicating distribution primarily in extracellular fluid. |
| Bioavailability | Subcutaneous: approximately 89% absolute bioavailability. |
| Onset of Action | Subcutaneous: Glycemic effects begin within 2–4 weeks; weight loss onset is detectable after 4–8 weeks. |
| Duration of Action | Clinical effects persist for up to 5 weeks after last dose due to slow elimination; steady state is reached after 4–5 weeks of weekly dosing. |
| Molecular Weight | 4113.58 |
Subcutaneous injection 0.25 mg once weekly for 4 weeks, then increase to 0.5 mg once weekly for 4 weeks, then 1 mg once weekly for 4 weeks, then 1.7 mg once weekly for 4 weeks, then maintenance 2.4 mg once weekly.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²). Not recommended in end-stage renal disease (eGFR <15 mL/min/1.73 m²) due to limited experience. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh class A or B). Not studied in severe hepatic impairment (Child-Pugh class C); use with caution. |
| Pediatric use | Not approved for pediatric patients under 12 years of age. For adolescents aged 12-17 years with BMI ≥95th percentile, same dosing titration as adults: start 0.25 mg once weekly, escalate to maintenance 2.4 mg once weekly. |
| Geriatric use | No specific dose adjustment required based on age alone. Monitor renal function in elderly patients as they are more likely to have impaired renal function. Initiate at lowest dose and titrate slowly. |
| 1st trimester | There are no adequate and well-controlled studies in pregnant women. Animal studies have shown reproductive toxicity. Use only if potential benefit justifies potential risk to the fetus. |
| 2nd trimester | Same as T1. Semaglutide may cause fetal harm based on animal data showing reduced fetal growth and increased skeletal abnormalities. |
| 3rd trimester | Same as T1 and T2. Due to potential for fetal harm, especially during organogenesis and late gestation, avoid use unless absolutely necessary. |
Clinical note
Comprehensive clinical and safety monograph for WEGOVY (WEGOVY).
| Placental transfer | Based on animal studies, semaglutide crosses the placenta. In humans, the degree is unknown but expected due to molecular weight and similarity to other peptides. |
| Breastfeeding | It is unknown whether semaglutide is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Personal or family history of medullary thyroid carcinomaMultiple Endocrine Neoplasia syndrome type 2 (MEN-2)Known hypersensitivity to semaglutide or any excipients
| Precautions | Risk of thyroid C-cell tumors (medullary thyroid carcinoma) based on animal data; contraindicated in personal/family history of MTC or MEN2, Acute pancreatitis: Discontinue if suspected, Severe gastrointestinal adverse reactions: Nausea, vomiting, diarrhea, constipation; may cause dehydration and renal impairment, Acute gallbladder disease (cholelithiasis, cholecystitis), Hypoglycemia: Especially when used with insulin or sulfonylureas, Increased heart rate: Monitor, Diabetic retinopathy complications (in type 2 diabetes trials): Advise monitoring, Fetal risk: Avoid during pregnancy; advise contraception |
| Food/Dietary | No specific food interactions. WEGOVY may be administered with or without meals. However, high-fat meals may exacerbate gastrointestinal side effects such as nausea, vomiting, and diarrhea. Advise patients to avoid high-fat foods, especially during dose escalation. WEGOVY delays gastric emptying, which can alter the absorption of oral medications; patients should be monitored when initiating or changing WEGOVY dose, particularly for drugs requiring precise absorption (e.g., oral contraceptives, antibiotics, thyroid hormones). No restriction on alcohol consumption, but alcohol can cause hypoglycemia or exacerbate GI symptoms. |
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| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | Based on animal studies, semaglutide (Wegovy) is associated with fetal toxicity, including structural abnormalities and reduced growth, at clinically relevant exposures. There are no adequate human studies in pregnant women. First-trimester exposure may pose a risk of major congenital malformations. Second and third trimester use may affect fetal growth and development. Due to the long half-life of semaglutide, women of childbearing potential should discontinue Wegovy at least 2 months before planned pregnancy. |
| Fetal Monitoring | Monitor weight changes, blood glucose levels, and potential gastrointestinal adverse effects in the mother. In the event of inadvertent pregnancy exposure, perform detailed fetal ultrasound to assess for structural anomalies. Monitor fetal growth via serial ultrasounds if exposure continues into second or third trimester. |
| Fertility Effects | In animal studies, semaglutide caused delayed estrus and reduced fertility at clinically relevant doses. In humans, weight loss associated with semaglutide may improve fertility in anovulatory women with obesity. However, the effect on ovulation induction and fertility outcomes has not been systematically studied. Women of childbearing potential should use effective contraception during treatment and for at least 2 months after discontinuation. |
| Clinical Pearls | WEGOVY (semaglutide) is a GLP-1 receptor agonist for chronic weight management. Start at 0.25 mg subcutaneously once weekly for 4 weeks, then titrate to 0.5 mg, 1.0 mg, 1.7 mg, and 2.4 mg at 4-week intervals as tolerated. Administer on the same day each week, any time of day, with or without meals. Monitor for gastrointestinal adverse effects (nausea, vomiting, diarrhea, constipation) which are common, especially during dose escalation. Counsel patients to stop eating when full to reduce nausea. WEGOVY can slow gastric emptying, potentially affecting absorption of oral medications; monitor patients on concomitant oral drugs, especially those with narrow therapeutic indices. Contraindicated in personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN-2). Avoid use in patients with history of pancreatitis. WEGOVY is not indicated for type 1 diabetes or diabetic ketoacidosis. |
| Patient Advice | WEGOVY is a once-weekly injection for chronic weight management in adults with obesity or overweight with at least one weight-related comorbidity. · Administer subcutaneously in the abdomen, thigh, or upper arm on the same day each week. Rotate injection sites. · If you miss a dose and the next scheduled dose is more than 2 days away, take the missed dose as soon as possible. If less than 2 days, skip the missed dose and resume normal schedule. · Common side effects include nausea, vomiting, diarrhea, constipation, and abdominal pain. These often improve over time. Eating smaller, low-fat meals and avoiding high-fat foods may help. · Stop eating when you feel full to reduce nausea and vomiting. · Tell your doctor if you have severe stomach pain that does not go away; this may be a sign of pancreatitis. · WEGOVY may cause thyroid tumors including medullary thyroid carcinoma. Seek medical attention if you develop a lump or swelling in the neck, hoarseness, trouble swallowing, or shortness of breath. · WEGOVY is not for use in people with type 1 diabetes. · Store WEGOVY in the refrigerator between 36°F to 46°F (2°C to 8°C). Do not freeze. If needed, you can store at room temperature (up to 86°F/30°C) for up to 28 days. |