Is Rybelsus (semaglutide) suitable for a patient with a body mass index (BMI) indicating overweight?

Semaglutide (Rybelsus) for Overweight Patients

Semaglutide (Rybelsus) is appropriate for patients with a BMI ≥27 kg/m² who have at least one weight-related comorbidity, or for patients with a BMI ≥30 kg/m² regardless of comorbidities. 1, 2

Indications and Patient Selection

• Pharmacotherapy is recommended for patients who have not responded adequately to lifestyle interventions and have:
  • BMI ≥30 kg/m² (regardless of comorbidities)
  • BMI ≥27 kg/m² with at least one weight-related comorbidity (hypertension, dyslipidemia, type 2 diabetes, etc.) 1
  • For Asian populations, lower BMI thresholds (≥23 kg/m²) should be considered 3

Efficacy for Weight Management

Semaglutide has demonstrated significant efficacy for weight management:

• Oral semaglutide (Rybelsus) at 14 mg daily has shown modest weight loss of approximately 5.7% (5.9 kg) after one year in real-world studies 4
• Higher doses show more substantial results:
  • Oral semaglutide 25 mg daily: 13.6% weight reduction at 64 weeks 5
  • Injectable semaglutide 2.4 mg weekly: 14.9-15.2% weight reduction at 68-104 weeks 6, 7

Dosing and Administration

For Rybelsus (oral semaglutide):

• Start with 3 mg once daily for 30 days
• Increase to 7 mg once daily for at least 30 days
• May increase to 14 mg once daily if needed for glycemic control
• Take on an empty stomach with no more than 4 ounces of plain water, at least 30 minutes before the first food, beverage, or other oral medications of the day

Mechanism of Action

Semaglutide works through multiple mechanisms:

• Delays gastric emptying, increasing satiety
• Reduces appetite through central nervous system effects
• Promotes glucose-dependent insulin secretion
• Suppresses glucagon secretion in a glucose-dependent manner 8

Monitoring and Follow-up

• Evaluate weight loss response after 12 weeks on the maximum tolerated dose
• If <5% weight loss is achieved after 12 weeks, consider discontinuation or alternative therapy 1
• For maintenance, continue medication long-term at the lowest effective dose, as discontinuation typically results in significant weight regain 3
• Follow-up should occur at least quarterly to monitor:
  • Weight stability or continued gradual loss
  • Side effect management
  • Medication adherence

Adverse Effects

The most common adverse effects are gastrointestinal:

• Nausea (most common)
• Vomiting
• Diarrhea
• Abdominal pain
• Constipation

Management strategies include:

• Starting at a low dose and titrating slowly
• Reducing meal size
• Avoiding high-fat diets
• Limiting alcohol and carbonated drinks 3

Contraindications and Precautions

Semaglutide is contraindicated in:

• Personal or family history of medullary thyroid carcinoma
• Multiple endocrine neoplasia syndrome type 2
• Pregnancy
• Breastfeeding

Use with caution in patients with:

• History of pancreatitis
• Gallbladder disease
• Gastroparesis 3, 8

Clinical Pearls

• Semaglutide has shown cardiovascular benefits in addition to weight loss
• No dose adjustment is required for patients with renal impairment
• For optimal results, combine with lifestyle interventions (diet and physical activity)
• The Mexican clinical practice guidelines emphasize individualization of pharmacotherapy based on comorbidities and safety considerations 1
• Long-term treatment is necessary for sustained weight management, as weight regain is common when medication is discontinued 3