Sublingual Liraglutide Phase Ib/IIa Trial Investigates Safety and Preliminary Efficacy in Type 2 Diabetes Mellitus

Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and impaired insulin secretion, leading to hyperglycemia. Glucagon-like peptide-1 receptor (GLP-1R) agonists like liraglutide are highly effective in managing T2DM by enhancing glucose-dependent insulin secretion, suppressing glucagon, and promoting satiety. However, current GLP-1R agonists are primarily administered via subcutaneous injection, which can be a barrier to long-term adherence for many patients. Developing an effective oral or sublingual formulation could significantly improve patient convenience and compliance, addressing a critical unmet need in T2DM management.

This Phase Ib/IIa, single ascending dose, randomized, double-blind, placebo-controlled study is recruiting 15 patients with Type 2 Diabetes Mellitus who have not previously received liraglutide. Part 1 (open-label, n=3) involves subjects receiving three single ascending doses of SL liraglutide (3, 12, 30 mg) and subcutaneous (SC) liraglutide (active comparator), each followed by a mixed meal tolerance test (MMTT) and a 1-week washout. Part 2 (investigator-blind, n=12) will randomize subjects to receive one of three SL-liraglutide doses (determined from Part 1), SL-placebo, or SC liraglutide, also with MMTT and 1-week washouts. The primary outcomes focus on safety, tolerability, and preliminary efficacy.

As this is an active, recruiting Phase Ib/IIa clinical trial (NCT ID: NCT05268237), specific efficacy and safety data are not yet available. The study is designed to establish the safety profile and tolerability of a novel sublingual formulation of liraglutide across various doses. Researchers aim to determine the optimal sublingual dose that demonstrates preliminary efficacy in improving glucose metabolism, as assessed by MMTT results, and to compare its pharmacokinetic and pharmacodynamic profiles against the established subcutaneous formulation. The preliminary efficacy endpoints will likely include changes in post-meal glucose and insulin levels, providing initial insights into its therapeutic potential. This trial is a crucial step in evaluating the potential for a non-injectable GLP-1R agonist.