Oral Insulin Delivery: Translational Barriers, Clinical Evidence, and Emerging Engineering Strategies in Diabetes Management

Abstract

Diabetes mellitus now affects more than 530 million people worldwide, which creates a growing global health crisis that overwhelms medical facilities. Type 1 diabetes and advanced type 2 diabetes patients use subcutaneous insulin as their primary treatment method, yet injection pain, needle phobia, and treatment adherence problems prevent them from achieving the best blood sugar control results. The review evaluates the development of oral insulin technology, which includes enteric-coated capsules and absorption enhancer systems, nanoparticle-based carriers, mucoadhesive platforms, and glucose-responsive smart polymers. The advanced candidates ORMD-0801 and insulin tregopil have entered late-phase clinical trials, which showed they could maintain safety, but their glycemic effects remained limited and unpredictable. The systems that use nanotechnology demonstrate better preclinical bioavailability results, but researchers require additional human data to establish their effectiveness. The main obstacles to successful research translation into practice are enzyme destruction, inadequate epithelial absorption, unpredictable drug distribution, complex production processes, and individual patient differences in drug response. The development of new engineering methods aims to create approaches that improve targeted intestinal drug absorption, enhance hepatic first-pass metabolism, and establish glucose-responsive drug delivery systems that will reduce hypoglycemic events. Advances in drug delivery technology will make oral insulin a practical option for type 2 diabetes once it is established as an alternative to injections. The clinical use of this system will rely on how effectively its formulation improvements, pharmacokinetic simulations, and extensive clinical trials work together for testing