WEGOVY HD
Clinical safety rating: caution
Comprehensive clinical and safety monograph for WEGOVY HD (WEGOVY HD).
WEGOVY (semaglutide) is a glucagon-like peptide-1 (GLP-1) receptor agonist that increases insulin secretion, decreases glucagon secretion, delays gastric emptying, and promotes satiety.
| Metabolism | Semaglutide is metabolized via proteolytic cleavage of the peptide backbone and beta-oxidation of the fatty acid side chain. It is not significantly metabolized by CYP450 enzymes. |
| Excretion | Primarily renal elimination of intact peptide; ~47% excreted unchanged in urine, remainder via fecal/biliary routes (≈38%). |
| Half-life | Terminal elimination half-life approximately 165 hours (≈7 days), supporting once-weekly dosing. |
| Protein binding | Highly protein bound (>99%), primarily to albumin. |
| Volume of Distribution | Volume of distribution: approximately 0.7 L/kg, indicating limited extravascular distribution. |
| Bioavailability | Subcutaneous: absolute bioavailability approximately 89%. |
| Onset of Action | Subcutaneous injection: onset of glucose-lowering effect within 2–3 weeks; maximal effect on weight loss typically observed after 8–12 weeks. |
| Duration of Action | Duration of action: ~1 week after single subcutaneous dose, consistent with weekly dosing interval; sustained metabolic effects for up to 2 weeks post-dose. |
Subcutaneous injection once weekly. Initiate at 0.25 mg weekly for 4 weeks, then increase to 0.5 mg weekly for 4 weeks, then 1 mg weekly for 4 weeks, then 1.7 mg weekly for 4 weeks, then maintain at 2.4 mg weekly.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73m²). Limited data in severe impairment (eGFR <30 mL/min/1.73m²) and end-stage renal disease; use with caution. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh class A). Limited data in moderate (Child-Pugh class B) and severe impairment (Child-Pugh class C); use with caution. |
| Pediatric use | Not approved for use in pediatric patients. Safety and efficacy not established. |
| Geriatric use | No specific dose adjustment recommended. Caution due to increased risk of adverse effects (e.g., gastrointestinal) in elderly patients with comorbidities or concomitant medications. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for WEGOVY HD (WEGOVY HD).
| Breastfeeding | Unknown if excreted in human milk; M/P ratio not determined. Caution advised; consider benefits vs risks. |
| Teratogenic Risk | First trimester: Limited human data; animal studies show embryotoxicity at high doses. Avoid use. Second/third trimester: Not recommended due to potential fetal harm from maternal weight loss and nutritional deficiency. |
| Fetal Monitoring |
■ FDA Black Box Warning
There is no black box warning for WEGOVY. However, semaglutide products have a boxed warning regarding the risk of thyroid C-cell tumors (medullary thyroid carcinoma) based on animal studies.
| Serious Effects |
Personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2); hypersensitivity to semaglutide or any excipients.
| Precautions | Risk of thyroid C-cell tumors; acute pancreatitis; acute gallbladder disease; hypoglycemia when used with insulin or insulin secretagogues; acute kidney injury; hypersensitivity reactions; diabetic retinopathy complications (in patients with type 2 diabetes); suicidal behavior or ideation; heart rate increase. |
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| Monitor fetal growth and development via ultrasound; assess maternal weight, nutritional status, and glycemic control. |
| Fertility Effects | May impair fertility due to delayed gastric emptying and altered nutrient absorption; reversible upon discontinuation. |