Oral semaglutide's safety, tolerability, and pharmacokinetics profile established in Phase 1 trial

Type 2 Diabetes (T2D) is a chronic metabolic disorder characterized by insulin resistance and impaired insulin secretion, leading to hyperglycemia. Glucagon-like peptide-1 (GLP-1) receptor agonists are highly effective in T2D management, promoting glucose-dependent insulin release, suppressing glucagon, and slowing gastric emptying. While injectable GLP-1 analogues like semaglutide are well-established, an oral formulation offers significant advantages in patient convenience and adherence, addressing a key barrier to broader adoption of this potent therapeutic class. This study aimed to evaluate an oral semaglutide formulation.

This Phase 1, randomized, double-blind, placebo-controlled trial enrolled 107 healthy male subjects and male subjects with Type 2 Diabetes (T2D) in Europe. Participants received multiple daily oral doses of semaglutide at start doses of 5 mg and 10 mg, escalating to end doses of 20 mg, 40 mg, or 60 mg. A placebo arm was included. The primary endpoint was the number of treatment emergent adverse events (TEAEs) recorded from first dosing until completion of post-treatment follow-up (Day 90-104), assessing safety and tolerability. Secondary endpoints included plasma concentration curve (AUC) for pharmacokinetics and changes from baseline in fasting plasma glucose (FPG) and C-peptide for pharmacodynamics.

This Phase 1 clinical trial aimed to investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of multiple oral doses of a long-acting GLP-1 analogue, semaglutide, in healthy male subjects and male subjects with Type 2 Diabetes. The study design included the measurement of treatment emergent adverse events (TEAEs) as the primary safety outcome, alongside plasma concentration curve (AUC) to assess drug exposure and fasting plasma glucose (FPG) and C-peptide levels to evaluate physiological effects. However, the provided abstract summary details the study's objectives and methods but does not present specific quantitative results regarding the observed safety profile, PK parameters, or PD changes. Therefore, no specific percentages, p-values, or fold-changes from the study's findings can be reported here.