Diabetes and metabolic dysfunction represent growing global health challenges, and current therapies mitigate hyperglycemia without sufficiently altering the underlying disease processes. Rapid advances in regenerative medicine, gene editing, and nano-enabled drug delivery are reshaping therapeutic possibilities, offering the potential to restore β-cell function, enhance insulin sensitivity, and personalize care at an unprecedented scale. This review synthesizes emerging therapeutic strategies with the greatest translational promise, including stem cell-derived islet replacement, immune-evasive encapsulation devices, CRISPR-based gene correction, and targeted or glucose-responsive nanocarriers engineered for noninvasive insulin delivery. Complementary advances in multi-omics profiling, proteogenomics, microbiome science, and artificial intelligence are enabling stratification of patients based on molecular signatures, optimizing therapeutic selection, and predicting clinical outcomes. Despite remarkable breakthroughs—such as the early-phase clinical success of stem cell-derived β-cell replacement and organ-targeted lipid nanoparticles (LNPs)—significant barriers remain, including immunogenicity, off-target editing, scalability, ethical concerns, and long-term safety. By integrating mechanistic insights with translational developments, this review outlines a forward-looking perspective on next-generation treatments poised to shift diabetes care from glycemic management toward disease modification and personalized metabolic restoration.
Spanorriga et al. (Sun,) studied this question.