Oral Semaglutide, A New Option in the Management of Type 2 Diabetes Mellitus: A Narrative Review

Abstract

According to current guidelines, glucagon-like peptide-1 (GLP-1) receptor agonists are the antidiabetic agent of choice in patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease (CVD) and are also the preferable antidiabetic agent in patients with T2DM without CVD but with indicators of high cardiovascular risk. A limitation in the use of GLP-1 receptor agonists is that they are delivered by subcutaneous injections. In this context, the development of an orally administered formulation of semaglutide offers an additional option in the management of patients with T2DM. In the present review, we discuss the findings of the main trials that evaluated the safety and efficacy of oral semaglutide. Oral semaglutide appears to be more effective in reducing HbA 1c levels and body weight than other antidiabetic agents and similarly effective to other GLP-1 receptor agonists. The safety profile of oral semaglutide is also comparable with other members of its class. Even though oral semaglutide did not reduce the incidence of the composite primary endpoint in a randomized controlled trial, a reduction in cardiovascular and all-cause mortality was observed. Therefore, oral semaglutide appears to represent a useful tool in the management of patients with TD2M, particularly those with established CVD or high cardiovascular risk and unwilling to receive injectable GLP-1 receptor agonists.

Untitled

“…This phase 3 clinical research program comprised 8 10 international studies (PIONEER 1-10) [6,10,42,55,[61][62][63][76][77][78][79]. In these trials, oral semaglutide in three different doses of 3, 7 and 14 mg were examined in comparison to placebo (PIONEER 1, 8, and 4 -6), sitagliptin in dose of 100 mg (PIONEER 3 and 7), empagliflozin in dose of 25 mg (PIONEER 2), liraglutide (PIONEER 4, 9) and dulaglutide (PIONEER 10) [3,68,69] (Table II).…”

“…Tirzepatide is a novel and the first dual association between a GLP-1 and a Glucose-dependent Insulinotropic Peptide (GIP) RA recommended in obese patients, administered subcutaneously once weekly, which provides consistent and persistent reductions in body weight [25]. It is generally known that among patients with DM oral medications tend to have higher rates of therapy adherence than injectable ones, which could represent a limitation of GLP-1 RAs usage [19,68]. The first oral formulation of the GLP-1 analogue, oral semaglutide has been developed for once-daily administration, in which a molecule called SNAC (sodium N-(8-[2-hydroxybenzoyl] amino) caprylate) enhances the absorption of the active ingredient through gastric mucosa [8,21].…”

“…The first oral formulation of the GLP-1 analogue, oral semaglutide has been developed for once-daily administration, in which a molecule called SNAC (sodium N-(8-[2-hydroxybenzoyl] amino) caprylate) enhances the absorption of the active ingredient through gastric mucosa [8,21]. In this context, the invention of a semaglutide formulation for oral administration, represents a supplementary variant for patients with obesity and DM [68].…”

Best Achievements in Clinical Medicine in Diabetes and Dyslipidemia in 2020

“…Semaglutide, a GLP-1RA with once-weekly injection that was approved in patients with T2DM, showed a consistently significant reduction in HbA1c in the Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN) clinical trials [28]. Oral semaglutide, a co-formulation with the absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate, is the first oral GLP-1RA that has been approved for clinical use for improving glycemic control in patients with T2DM in the United States [29].…”

Newer Vistas in glucagon-like peptide-1 analog therapy - Marvels of peptide engineering

“…Finally, SNAC also promotes monomerization of the peptide making it easier for semaglutide to move across the fluidized mucosa and get absorbed into the portal circulation. [ 6 ]…”