What are the oral GLP-1 (Glucagon-Like Peptide-1) receptor agonists, including their doses, for the treatment of type 2 diabetes?

Oral GLP-1 Receptor Agonists with Dosing Information

Currently, semaglutide is the only FDA-approved oral GLP-1 receptor agonist, available as Rybelsus with doses of 3 mg, 7 mg, and 14 mg once daily. 1

Oral Semaglutide (Rybelsus)

• Starting dose: 3 mg once daily for 30 days 1
• Maintenance doses: Titrate to 7 mg once daily, then to 14 mg once daily based on glycemic response and tolerability 1
• Administration: Must be taken on an empty stomach with no more than 4 oz of plain water, at least 30 minutes before the first food, beverage, or other oral medications of the day 2, 1
• Efficacy: Provides HbA1c reductions of 0.9%, 1.2%, and 1.4% with 3 mg, 7 mg, and 14 mg doses respectively 1
• Weight loss effects: Produces significant weight reduction of 2.6-4.4 kg at the 14 mg dose 3, 4

Clinical Considerations

• Oral semaglutide has demonstrated superior glycemic control compared to sitagliptin (DPP-4 inhibitor) and similar efficacy to injectable GLP-1 receptor agonists 3, 4
• The 14 mg dose provides the greatest efficacy for both glycemic control and weight loss 1
• Gastrointestinal side effects are dose-dependent and typically occur early in treatment, diminishing over time 5, 1
• Common adverse effects include nausea (15-20% with 14 mg dose), vomiting, diarrhea, dyspepsia, and constipation 5, 1

Important Precautions

• Contraindications: Personal or family history of medullary thyroid cancer, Multiple Endocrine Neoplasia syndrome type 2, pregnancy, or breastfeeding 5, 2
• Cautions: History of pancreatitis (consider alternative therapy), risk of gallbladder disorders 5, 2
• Hypoglycemia risk: Low when used as monotherapy but increased when combined with insulin or sulfonylureas 6, 1
• Cardiovascular benefits: Oral semaglutide has demonstrated cardiovascular risk reduction similar to injectable GLP-1 receptor agonists 7

Injectable GLP-1 Receptor Agonists for Comparison

While not oral formulations, the following injectable GLP-1 receptor agonists are available:

• Once-daily options:

  • Liraglutide (Victoza): 0.6 mg, 1.2 mg, 1.8 mg 5
  • Lixisenatide: 10 mcg, 20 mcg 5

• Once-weekly options:

  • Semaglutide (Ozempic): 0.25 mg, 0.5 mg, 1.0 mg, 2.4 mg 5
  • Dulaglutide (Trulicity): 0.75 mg, 1.5 mg 5, 8
  • Exenatide extended-release: 2 mg 5, 9

Future Developments

• Research continues on developing additional oral formulations of GLP-1 receptor agonists to overcome the challenges of peptide delivery through the gastrointestinal tract 9
• Combination therapies with oral GLP-1 receptor agonists and other oral antidiabetic medications are being studied to enhance efficacy while maintaining the convenience of oral administration 5