What is the recommended dosing and administration protocol for starting Wegovy (semaglutide)?

Starting Wegovy: Dosing and Administration Protocol

Begin Wegovy at 0.25 mg subcutaneously once weekly for 4 weeks, then escalate the dose every 4 weeks through 0.5 mg, 1.0 mg, and 1.7 mg, until reaching the maintenance dose of 2.4 mg once weekly. 1

Dose Titration Schedule

The gradual escalation protocol is mandatory to minimize gastrointestinal side effects:

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

This 16-week titration period allows gastrointestinal tolerance to develop and significantly reduces the incidence of nausea (44%) and vomiting (25%) that occur at maximal doses. 2

Administration Details

Inject subcutaneously in the abdomen, thigh, or upper arm once weekly at any time of day, with or without meals. 1, 3

Missed Dose Management

• If less than 5 days since missed dose: Administer as soon as possible 1
• If more than 5 days have passed: Skip the missed dose and resume at next scheduled time 1
• If 2 consecutive doses missed: Resume at the same dose if previously well-tolerated, or consider lowering the dose 1
• If 3 or more consecutive doses missed: Restart the entire titration schedule 1

Storage Requirements

• Refrigerate at 36°F to 46°F (2°C to 8°C) 1
• May be kept at room temperature for up to 28 days 1

Managing Gastrointestinal Side Effects

The most common adverse events are gastrointestinal: nausea (44%), diarrhea (32%), vomiting (25%), and constipation (23%). 2 These are typically transient and mild-to-moderate in severity. 1

If severe gastrointestinal symptoms occur, maintain the current dose for longer than 4 weeks before continuing escalation. 2 The slow titration strategy is the most effective method to mitigate these symptoms. 2

Mandatory Lifestyle Interventions

Wegovy must be combined with lifestyle modifications—this is not optional:

• Caloric deficit: Minimum 500 kcal/day below total requirements 2
• Physical activity: Minimum 150 minutes weekly of structured exercise 2
• Behavioral counseling: Ongoing counseling about dietary changes 2

Drug Interactions and Contraindications

Do not use Wegovy with other GLP-1 receptor agonists or DPP-4 inhibitors. 1

When combining with insulin or sulfonylureas, monitor closely for hypoglycemia and adjust doses of these medications as needed. 1 Wegovy delays gastric emptying and may impact absorption of oral medications requiring rapid onset. 4

Special Populations

• Renal impairment: No dosage adjustment required, including end-stage renal disease 1
• Hepatic impairment: Use with caution in severe hepatic impairment due to limited experience 4
• Elderly patients: No specific dose adjustment needed 4

Treatment Duration and Response

Consider Wegovy as lifelong therapy to maintain weight loss. 2 Discontinuation results in significant weight regain. 2 In clinical trials, mean weight loss was 14.9% versus 2.4% with placebo at 68 weeks, with 86.4% of participants achieving ≥5% weight loss and 50.5% achieving ≥15% weight loss. 5

Some patients achieve adequate response at submaximal doses (0.5 mg, 1.0 mg, or 1.7 mg) and can continue that dose long-term rather than escalating to 2.4 mg. 1

Monitoring Requirements

• Body weight: Every 4 weeks during titration 2
• Gastrointestinal symptoms: At each visit 2
• Glucose levels: More closely if patient has concomitant type 2 diabetes 2
• Nutritional status: Ongoing assessment 2

Additional Cardiovascular Benefits

Beyond weight loss, Wegovy provides weight-independent benefits including improvements in blood pressure, atherogenic lipids, inflammation, and reduces major adverse cardiovascular events in patients with obesity and established cardiovascular disease. 2