Can Rybelsus (semaglutide) be used for weight loss?

Rybelsus (Semaglutide) for Weight Loss

Semaglutide (Rybelsus) is effective for weight loss, with clinical trials showing 14.9-16.0% weight reduction at 68 weeks with the 2.4mg weekly injectable form, though the oral formulation (Rybelsus) is currently only FDA-approved for diabetes management, not specifically for weight loss. 1

Efficacy of Semaglutide for Weight Loss

Semaglutide has demonstrated substantial weight loss benefits in clinical trials:

• The STEP 1 trial showed a mean weight reduction of 14.9% from baseline at 68 weeks with weekly 2.4mg semaglutide injections compared to only 2.4% with placebo 2
• Significantly more participants achieved clinically meaningful weight loss with semaglutide:
  • 86.4% lost ≥5% of body weight
  • 69.1% lost ≥10% of body weight
  • 50.5% lost ≥15% of body weight 2

While these impressive results are from the injectable form, the oral formulation (Rybelsus) is not currently FDA-approved specifically for weight management.

Regulatory Status and Indications

• Injectable semaglutide (Wegovy) at 2.4mg weekly was FDA-approved in 2021 specifically for chronic weight management 3
• Oral semaglutide (Rybelsus) is currently only approved for type 2 diabetes management 3
• Weight management indications are for adults with:
  • BMI ≥30 kg/m² or
  • BMI ≥27 kg/m² with at least one weight-related comorbidity 1

Mechanism of Action for Weight Loss

Semaglutide promotes weight loss through several mechanisms:

• Acts on GLP-1 receptors in the hypothalamus to reduce hunger and food cravings 1
• Enhances feelings of fullness after meals through improved satiety signals 1
• Delays gastric emptying, though this effect may diminish over time due to tachyphylaxis 4

Important Considerations for Use

Duration of Therapy

• Semaglutide should be considered a long-term therapy for weight management 1
• Significant weight regain occurs after discontinuation, as demonstrated in the STEP 4 trial where participants who switched to placebo after 20 weeks regained 6.9% of body weight 5

Response Assessment

• Effectiveness should be monitored monthly for the first 3 months 1
• Early responders (>5% weight loss after 3 months) show improved long-term outcomes 1
• If inadequate response (<5% weight loss after 3 months), reevaluation of treatment approach is necessary 1

Side Effects and Safety

• Gastrointestinal symptoms are the most common adverse events:
  • Nausea, vomiting, diarrhea, and constipation 1
  • These are typically transient and mild-to-moderate in severity 2
• More serious but less common adverse events include:
  • Pancreatitis
  • Diabetic retinopathy
  • Severe allergic reactions 3

Additional Health Benefits

Beyond weight loss, semaglutide offers several cardiometabolic benefits:

• Reduces cardiovascular death, heart attacks, and strokes by 20% in adults with obesity or overweight and cardiovascular disease 1
• Decreases blood pressure and improves cholesterol profiles 1
• May benefit patients with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) 4

Practical Approach

For optimal results with semaglutide for weight management:

1. Start with appropriate patient selection (BMI ≥30 or ≥27 with comorbidities)
2. Begin with the lowest dose and gradually titrate to minimize gastrointestinal side effects
3. Combine with lifestyle modifications (reduced-calorie diet and physical activity) for maximum effectiveness 1
4. Assess response after 3 months; continue if ≥5% weight loss is achieved
5. Plan for long-term therapy as weight regain is common after discontinuation

Limitations and Caveats

• Oral semaglutide (Rybelsus) is not currently FDA-approved specifically for weight loss
• Supply issues have been reported due to high demand 3
• Treatment should be continued indefinitely for sustained benefits, as weight regain occurs after discontinuation 1, 5
• Contraindicated in pregnancy and should be used with caution in patients with history of pancreatitis or gallbladder disease 1