What is the recommended dosing schedule for Wegovy (semaglutide) in a patient with impaired renal function or a history of pancreatitis or thyroid cancer?

Wegovy Dosing Schedule

Wegovy (semaglutide 2.4 mg) follows a standardized 16-week titration schedule starting at 0.25 mg once weekly for 4 weeks, escalating through 0.5 mg, 1.0 mg, and 1.7 mg (each for 4 weeks), reaching the maintenance dose of 2.4 mg once weekly. 1

Standard Titration Protocol

The FDA-approved escalation schedule is designed to minimize gastrointestinal side effects while achieving therapeutic dosing: 1

• Weeks 1-4: 0.25 mg once weekly
• Weeks 5-8: 0.5 mg once weekly
• Weeks 9-12: 1.0 mg once weekly
• Weeks 13-16: 1.7 mg once weekly
• Week 17 onward: 2.4 mg once weekly (maintenance dose) 1

This gradual 16-week titration allows gastrointestinal tolerance to develop and minimizes adverse events like nausea and diarrhea. 1

Special Populations and Dosing Adjustments

Renal Impairment

No dose adjustment is required for Wegovy in patients with any degree of renal impairment, including end-stage renal disease (ESRD). 2 Renal impairment does not impact semaglutide pharmacokinetics in a clinically relevant manner, as demonstrated in studies comparing patients with mild, moderate, severe renal impairment and ESRD to those with normal renal function. 2

However, careful monitoring is essential in patients with severe renal impairment due to increased risk of acute kidney injury from dehydration secondary to gastrointestinal side effects. 3 Monitor renal function closely when initiating or escalating doses, especially in patients reporting severe gastrointestinal reactions. 3

History of Pancreatitis

Wegovy should be used with extreme caution in patients with a history of pancreatitis, and is not recommended if pancreatitis is suspected or confirmed. 4, 3 While acute pancreatitis has been reported in clinical trials, causality has not been definitively established. 4 If pancreatitis is suspected during treatment, discontinue Wegovy immediately and do not restart if pancreatitis is confirmed. 4

Thyroid Cancer Considerations

Wegovy is absolutely contraindicated in patients with personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). 3, 2 This carries an FDA Black Box Warning based on rodent studies showing thyroid C-cell tumors, though human relevance has not been determined. 3, 2

In the 2-year carcinogenicity studies, semaglutide caused statistically significant increases in thyroid C-cell adenomas and carcinomas in both mice and rats at clinically relevant exposures. 2 While human relevance remains unknown, this contraindication is absolute and non-negotiable. 3

Missed Dose Management

If a patient misses doses, the approach depends on duration and tolerance history: 1

• If fewer than 3 consecutive doses are missed and the patient previously tolerated the medication well, resume at the same dose 5
• If 3 or more consecutive doses are missed, consider restarting the titration schedule rather than resuming at the previous dose, especially at the 1.7 mg level 1, 5

Administration Instructions

Wegovy is administered as a once-weekly subcutaneous injection in the abdomen, thigh, or upper arm, with similar exposure achieved at all sites. 2 The injection can be given at any time of day, with or without meals. 2

Long-Term Treatment Considerations

Lifelong treatment is likely necessary for sustained weight management. 1 Clinical trial data demonstrate that participants who discontinued semaglutide regained significant weight, indicating the need for continuous therapy. 1

If a patient has not lost at least 5% of baseline body weight after 12 weeks on the maintenance dose (2.4 mg), discontinue Wegovy as they are likely a poor responder. 4

Monitoring Requirements

Regular monitoring should include: 3

• Renal function, particularly with severe gastrointestinal symptoms that could lead to dehydration 3
• Signs of pancreatitis (severe abdominal pain) 3
• Gallbladder disease symptoms (right upper quadrant pain) 3
• Diabetic retinopathy progression in high-risk patients (those with diabetes duration ≥10 years) 4

Critical Safety Considerations

Additional absolute contraindications include: 3

• Pregnancy or breastfeeding 3
• Active or suspected pancreatitis 3

Use with extreme caution in patients with: 3

• Severe gastroparesis (semaglutide delays gastric emptying) 3
• History of diabetic retinopathy requiring close monitoring 4
• Concurrent use of insulin or sulfonylureas (increased hypoglycemia risk requiring dose reduction of these agents) 4, 3