Oral GLP-1 Receptor Agonist
Semaglutide (Rybelsus®) is the only oral GLP-1 receptor agonist currently available. 1, 2
Formulation and Mechanism
Oral semaglutide is co-formulated with sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC), an absorption enhancer that facilitates peptide absorption across the gastric epithelium in the acidic stomach environment. 2, 3
This represents a significant pharmaceutical achievement, as GLP-1 peptides are typically degraded in the gastrointestinal tract and have extremely poor oral bioavailability without enhancement technology. 4
The semaglutide molecule itself has 94% homology to human GLP-1 and binds to GLP-1 receptors on pancreatic β-cells to stimulate glucose-dependent insulin secretion. 2, 5
Available Dosing
Oral semaglutide is available in three doses: 3 mg, 7 mg, and 14 mg, which are gradually titrated upward. 3
The 14 mg dose demonstrated superior HbA1c reduction compared to placebo, empagliflozin, dulaglutide, and sitagliptin, and was non-inferior to injectable liraglutide. 4
Clinical Context
All other GLP-1 receptor agonists mentioned in guidelines (exenatide, liraglutide, lixisenatide, beinaglutide, dulaglutide, semaglutide) require subcutaneous injection. 6
The development of an oral formulation addresses patient preference barriers and may facilitate earlier initiation of GLP-1 receptor agonist therapy in the type 2 diabetes treatment cascade. 2, 4
The safety profile is consistent with the injectable GLP-1 receptor agonist class, with gastrointestinal side effects (nausea, diarrhea) being most common, and cardiovascular safety demonstrated as non-inferior to placebo. 2, 3