The Journey and Excitement Following the Development of the First Peptide in a Pill: A Brief Overview of Pharmacology and Clinical Trials of Oral Semaglutide

Abstract

Oral semaglutide is the newest discovery, the first in class peptide in a pill. Sodium N-(8-[2-hydroxybenzoyl]amino)caprylate (SNAC), a small fatty acid, has been co-formulated with semaglutide, which facilitates its absorption from the gastric mucosa. It has 94% homology with human glucagon-like peptide 1 (GLP-1). It comes in three dose forms – 3 mg, 7 mg and 14 mg. It is given as once daily dosing and is recommended in adult type 2 diabetes mellitus patients as monotherapy when metformin is contraindicated or not tolerated and in combination with other oral antidiabetic drugs (OADs). In a phase 3 trial, it has been shown to reduce glycated hemoglobin (HbA1c) up to 1.5%, with weight reduction up to 5 kg with a 14 mg dose. There was nonsignificant risk reduction of 21% in 3-point major adverse cardiovascular events (MACE) and 51% and 49% risk reduction in cardiovascular (CV) deaths and all-cause mortality, respectively. Oral semaglutide was found to be superior to empagliflozin, sitagliptin and liraglutide in both glycemic control and weight reduction. It also exhibits many pleiotropic effects – reduced energy intake, anti-inflammatory and anti-atherosclerotic effect, to name a few. Nausea was the most common side effect which was experienced by only 15% to 20% of patients. It was mild-to-moderate and transient. Overall, oral semaglutide has shown its efficacy both early and late in the management of diabetes, irrespective of renal and hepatic impairment.