Management of Patients with Comorbidities

Introduction to Weight Management

• Obesity management involves the use of medications such as semaglutide (Wegovy) and liraglutide (Saxenda) for adults with BMI ≥30 kg/m² or BMI ≥27 kg/m² with at least one weight-related comorbidity, as approved by the FDA and recommended by the American Medical Association 1
• The American Diabetes Association strongly recommends continuing weight management medications long-term after achieving weight loss, as studies show significant weight regain with discontinuation, with a high evidence rating 2

Medications for Weight Management

• Semaglutide (Wegovy) at 2.4mg weekly and liraglutide (Saxenda) at 3.0mg daily are FDA-approved for weight management in adults with BMI ≥30 kg/m² or BMI ≥27 kg/m² with at least one weight-related comorbidity, resulting in 14.9-16.0% weight loss at 68 weeks for semaglutide and 8.0% weight loss at 56 weeks for liraglutide, as supported by the American Medical Association 1
• The efficacy of semaglutide and tirzepatide is summarized in the following table:

1, 3, 4

• Tirzepatide provides better value for money than semaglutide for weight reduction, with a cost needed to treat per 1% of body weight reduction of $985 (95% CI: $908-$1075) for tirzepatide, compared to $1845 (95% CI: $1707-$1989) for semaglutide, as studied in a cost-effectiveness analysis, with a moderate strength of evidence 5

Dosing and Titration

• The standard titration protocol for semaglutide is as follows:

• The American Diabetes Association recommends starting with a dose of 0.25 mg once weekly for the first 4 weeks, followed by gradual increments every 4 weeks until reaching the maintenance dose of 2.4 mg weekly, to minimize gastrointestinal side effects and optimize tolerability, with a moderate evidence rating 6, 7
• No dose adjustment is required in patients with renal impairment, including those with advanced renal insufficiency, as stated by the Endocrine Society, with a low evidence rating 6, 7

Adverse Effects and Management

• The following table summarizes the adverse effects and their management:

3

• Important contraindications include a personal or family history of medullary thyroid cancer, multiple endocrine neoplasia syndrome type 2, pregnancy, and precaution in patients with a history of pancreatitis or gallbladder disease, as supported by the American Heart Association, American Thyroid Association, and American College of Cardiology, with a high strength of evidence 8, 9, 3

Special Considerations

• Comprehensive liver function tests and assessment for non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) are recommended for patients with obesity, as suggested by the American Gastroenterological Association 10
• A structured weight loss program with dietary and lifestyle modifications is a suitable alternative weight management approach for patients with obesity, as recommended by the American Gastroenterological Association 10
• Lower BMI thresholds (≥23 kg/m²) should be considered for Asian populations, as recommended by the Asian Pacific Association for the Study of Obesity, with a low evidence rating 11
• Patients with renal impairment do not require special considerations or dose adjustments for semaglutide, as it does not depend on renal function 12

Maintenance and Discontinuation

• Discontinuation of therapy leads to weight regain, with 11.6% of lost weight regained after discontinuation, highlighting the importance of long-term use for maintaining weight loss, as recommended by medical guidelines 1
• For maintenance of weight loss with Ozempic (semaglutide), patients should continue the medication long-term at the lowest effective dose, as sudden discontinuation results in regain of 50-67% of weight loss within one year, with a moderate evidence rating 2