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. |
| Molecular Weight | 4116 |
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 | No adequate human data; animal studies show embryotoxicity at high doses; avoid use due to potential risk. |
| 2nd trimester | No adequate human data; animal studies show embryotoxicity; avoid use. |
| 3rd trimester | No adequate human data; animal studies show embryotoxicity; avoid use. |
Clinical note
Comprehensive clinical and safety monograph for WEGOVY HD (WEGOVY HD).
| Placental transfer | Likely minimal due to high molecular weight; however, not studied in humans. Theoretical transfer exists. |
| Breastfeeding | Unknown if distributed in human milk; potential for weight loss and GI effects in infant; advise caution or avoid breastfeeding during therapy. |
| Lactation Rating |
■ 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 |
Hypersensitivity to semaglutide or any excipientPersonal or family history of medullary thyroid carcinoma (MTC)Multiple endocrine neoplasia syndrome type 2 (MEN 2)
| 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. |
| Food/Dietary | No specific food restrictions. Wegovy slows gastric emptying which may affect absorption of oral medications; separate administration by at least 1 hour for medications requiring rapid absorption. Avoid high-fat meals immediately after injection to reduce nausea. |
Loading safety data…
| L4 (possibly hazardous) or Avoid |
| 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 | 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. |
| Clinical Pearls | Wegovy (semaglutide) is a GLP-1 receptor agonist for chronic weight management. Administer once weekly subcutaneously. Titrate gradually to minimize GI side effects. Contraindicated in medullary thyroid carcinoma and MEN-2. Monitor for pancreatitis, gallbladder disease, and suicidal ideation. |
| Patient Advice | Inject once weekly on the same day, with or without meals. · Common side effects include nausea, vomiting, diarrhea, and constipation; these often improve over time. · Stop Wegovy and seek medical help if you experience severe abdominal pain, vision changes, or signs of allergic reaction. · Do not share pens. Store in refrigerator, but can be kept at room temperature for up to 28 days. · Pregnancy: Not recommended; discontinue at least 2 months before planned conception. |