Type 2 diabetes mellitus imposes a pharmacological management challenge that extends beyond drug discovery to the fundamental question of how orally administered antidiabetic agents are delivered to their absorptive sites. Conventional formulations systematically underperform for a pharmacologically diverse drug class whose members include BCS Class II compounds with dissolution-limited bioavailability, agents with saturable proximal intestinal transport, and short-acting secretagogues requiring postprandial concentration peaks that standard tablet technology cannot reliably sustain. This review examines the gastrointestinal physiological basis for these failures, analyses how the T2DM disease state further distorts the absorptive environment through gastroparesis and GLP-1 receptor agonist-mediated motility changes, and critically evaluates the advanced oral delivery platforms developed to address them. Gastroretentive floating systems effervescent and non-effervescent, single-layer and bilayer are analysed mechanistically with evidence from published in vivo pharmacokinetic studies demonstrating up to 3.17-fold bioavailability improvements for narrow absorption window antidiabetics. Nanocarrier platforms including PLGA nanoparticles, solid lipid nanoparticles, and chitosan-coated nanoemulsions are evaluated against BCS-based selection logic, while mucoadhesive thiomers, stimuli-responsive systems, and phenylboronic acid-based glucose-responsive architectures are examined as next-generation concepts. Quality by Design frameworks, physiologically based pharmacokinetic modelling, and translational barriers spanning IVIVC limitations and regulatory ambiguity are addressed. The synthesis reveals that matching delivery platform to the dominant pharmacokinetic barrier of each drug class is the central organizing principle for next-generation oral antidiabetic formulation.
M.* et al. (Mon,) studied this question.