Wegovy (Semaglutide 2.4 mg) for Obesity Management

Indication

Wegovy is indicated for chronic weight management in adults with BMI ≥30 kg/m² or BMI ≥27 kg/m² with at least one weight-related comorbidity (hypertension, dyslipidemia, type 2 diabetes, obstructive sleep apnea, cardiovascular disease), and must be used as an adjunct to a reduced-calorie diet (500 kcal deficit) and minimum 150 minutes per week of physical activity. 1, 2

For patients with established cardiovascular disease and BMI ≥27 kg/m², Wegovy also reduces the risk of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke by 20% (HR 0.80) 1
No specific BMI threshold is required if the patient has type 2 diabetes, though Wegovy is preferred for patients with BMI >35 kg/m² due to superior weight loss benefits 1

Titration Schedule

Start at 0.25 mg weekly for 4 weeks, then escalate every 4 weeks: 0.5 mg (weeks 5-8), 1.0 mg (weeks 9-12), 1.7 mg (weeks 13-16), and reach the maintenance dose of 2.4 mg weekly after 16 weeks. 1

Missed Dose Protocol:

If ≤4 days since missed dose: administer as soon as possible 1
If >4 days since missed dose: skip and resume at next scheduled dose 1
If 2 consecutive doses missed: resume at same dose if previously tolerated 1
If ≥3 consecutive doses missed: consider restarting the titration schedule 1

Concomitant Medication Adjustments:

Reduce basal insulin by 20% immediately when initiating Wegovy to prevent hypoglycemia 1
Discontinue or reduce sulfonylurea doses by 50% when starting Wegovy 1
Do not use with other GLP-1 receptor agonists or DPP-4 inhibitors 1

Absolute Contraindications

Wegovy is absolutely contraindicated in patients with:

Personal or family history of medullary thyroid cancer 1, 3
Multiple endocrine neoplasia syndrome type 2 (MEN2) 1, 3
History of severe hypersensitivity reaction to semaglutide 1

Relative Cautions:

History of pancreatitis (use with caution, though causality not definitively established) 1
Severe gastroparesis or clinically meaningful GI motility disorders 1
Recent heart failure decompensation 1

Monitoring Parameters

During Titration Phase (First 16 Weeks):

Assess every 4 weeks for: 1

Gastrointestinal tolerance (nausea, vomiting, diarrhea)
Weight loss progress
Blood pressure (may require antihypertensive adjustment as weight decreases)
Signs of pancreatitis (persistent severe abdominal pain)
Signs of gallbladder disease (right upper quadrant pain)

Maintenance Phase (After Week 16):

Reassess at least every 3 months for: 1

Weight stability and continued weight loss progress
Cardiovascular risk factors (blood pressure, lipid panel)
Medication adherence
Adverse effects

Critical Decision Point at 12-16 Weeks:

If weight loss is <5% after 3 months at therapeutic dose, discontinue Wegovy and consider alternative approaches. 1

Expected Efficacy

Wegovy produces mean weight loss of 14.9-17.4% at 68 weeks, with 69-86% of patients achieving ≥10% weight loss and 51-64% achieving ≥15% weight loss. 3, 4, 5

Real-world data from the WeGoTogether program shows mean weight loss of -13.4% at 6 months, -17.6% at 12 months, -20.3% at 18 months, and -20.4% at 24 months 6
Weight loss is sustained over 104 weeks, with mean weight loss of -15.2% versus -2.6% with placebo 7
Weight loss appears greater in non-diabetic patients (14.9-17.4%) compared to those with type 2 diabetes (9.6%) 1, 5

Alternative Options if Wegovy Fails or Is Not Tolerated

If <5% Weight Loss After 3 Months at Maximum Dose:

First-line alternative: Switch to tirzepatide (Zepbound) 15 mg weekly, which achieves superior weight loss of 20.9% at 72 weeks. 1

Tirzepatide demonstrates 6% absolute advantage over semaglutide 2.4 mg 1
Discontinue Wegovy and initiate tirzepatide at 5 mg weekly, titrating every 4 weeks to maximum 15 mg weekly 1

Second-line alternative: Liraglutide 3.0 mg daily (Saxenda), which achieves 5.2-6.1% weight loss. 1

Consider if weekly injections are not tolerated 1
Less effective than Wegovy but may be suitable for patients requiring daily dosing flexibility 1

If Gastrointestinal Side Effects Are Intolerable:

Implement dietary modifications: 2

Take medication 15 minutes after a meal rather than on empty stomach 2
Reduce meal size and avoid high-fat, high-fiber foods during titration 2
Limit alcohol and carbonated beverages 2

If GI effects persist despite slow titration and dietary modifications, consider switching to tirzepatide, which has similar GI side effect profile but may be better tolerated in some patients. 1

If Wegovy Is Contraindicated or Unavailable:

Consider metabolic surgery if BMI ≥30 kg/m² with multiple severe obesity-related comorbidities requiring more aggressive intervention. 1

Common Pitfalls to Avoid

Do not advance dose escalation if persistent severe abdominal pain occurs (may indicate pancreatitis) 1
Do not discontinue Wegovy after achieving weight loss goals, as cessation results in regain of one-half to two-thirds of lost weight within 1 year 1
Do not use Wegovy within 3 weeks of elective surgery due to delayed gastric emptying and aspiration risk during anesthesia 1
Do not combine Wegovy with other GLP-1 receptor agonists due to overlapping mechanisms and potential harm 1
Do not wait longer than 3-4 months to assess initial treatment response, as early non-responders are unlikely to benefit from continued therapy 1

Lifelong Treatment Requirement

Wegovy must be used lifelong in conjunction with sustained lifestyle modifications, as sudden discontinuation results in significant weight regain (11.6% of lost weight regained after 52 weeks). 1

Patients should be counseled that this medication requires long-term commitment 1
Cost is approximately $1,557-$1,619 per 30-day supply 1
Insurance authorization may be challenging, particularly for obesity management without diabetes 1

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