Are there GLP-1 (Glucagon-like peptide-1) receptor agonist pills available?

Yes, Oral GLP-1 Receptor Agonist Pills Are Available

Oral semaglutide (Rybelsus®) is the first and currently only FDA-approved GLP-1 receptor agonist available in pill form, approved in 2019 for type 2 diabetes treatment. 1, 2

Available Oral Formulation

• Oral semaglutide is co-formulated with the absorption enhancer SNAC (sodium N-(8-[2-hydroxybenzoyl]amino) caprylate), which enables gastrointestinal absorption of this peptide medication that would otherwise be degraded 2, 3
• Available doses are 3 mg, 7 mg, and 14 mg tablets taken once daily 2, 3
• The 14 mg dose provides clinical effectiveness approaching that of the once-weekly subcutaneous semaglutide preparation 4

Clinical Efficacy

Oral semaglutide demonstrated non-inferiority to placebo for cardiovascular safety in the PIONEER 6 trial, which enrolled 3,183 patients with type 2 diabetes and high cardiovascular risk followed for a median of 15.9 months (HR 0.79; 95% CI 0.57–1.11) 1

• The PIONEER program showed oral semaglutide 14 mg reduced HbA1c significantly more than placebo, empagliflozin, dulaglutide, and sitagliptin, and was non-inferior to injectable liraglutide 2
• Superior body weight reductions were observed compared with placebo, sitagliptin, and liraglutide 2
• Demonstrated significant reductions in cardiovascular death and all-cause mortality versus placebo in PIONEER 6 2, 5

Dosing Strategy

Start at 3 mg daily for 30 days, then increase to 7 mg daily; if additional glycemic control is needed after at least 30 days on 7 mg, increase to 14 mg daily 6

• Must be taken on an empty stomach with no more than 4 ounces of water, at least 30 minutes before any food, beverage, or other oral medications 2
• Slow titration minimizes gastrointestinal side effects 6

Comparison to Injectable Formulations

While oral semaglutide provides a non-injectable option, injectable GLP-1 receptor agonists (liraglutide, dulaglutide, and subcutaneous semaglutide) have stronger cardiovascular outcome data showing statistically significant reductions in major adverse cardiovascular events 1

• Injectable semaglutide 2.4 mg weekly produces greater weight loss (14.9% mean reduction) compared to oral formulations 1
• Long-acting injectable GLP-1 receptor agonists have more profound effects on fasting plasma glucose and HbA1c 4

Clinical Positioning

Oral semaglutide represents a valuable option for patients preferring oral therapy and may lead to earlier GLP-1 receptor agonist initiation in the type 2 diabetes treatment continuum 2, 7

• Particularly suitable for initial phases of type 2 diabetes management 5
• The lack of robust positive cardiovascular outcome data (only non-inferiority demonstrated) is a limitation compared to injectable formulations with proven cardiovascular benefit 7