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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for WEGOVY (WEGOVY).
| Breastfeeding | No data exist on the presence of semaglutide in human milk, effects on the breastfed infant, or milk production. Semaglutide is a large peptide that is likely to be degraded in the infant's gastrointestinal tract and is poorly absorbed. However, due to potential for adverse effects on infant growth and development, breastfeeding is not recommended during Wegovy therapy. The M/P ratio is unknown. |
| 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. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Personal or family history of medullary thyroid carcinoma (MTC)","Multiple endocrine neoplasia syndrome type 2 (MEN2)","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"] |
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| 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. |