Current diabetes drugs: Lessons learned and implications for next-generation therapeutics
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GRAPHICAL ABSTRACT
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PUBLIC SUMMARY
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Insulin resistance and β-cell failure remain central therapeutic targets.
Incretin multi-agonists deliver unprecedented metabolic and weight-loss efficacy.
Lipid-metabolism and inflammation pathways offer emerging druggable nodes.
β-cell regeneration strategies show promise for disease-modifying therapy.
AI and multi-omics accelerate target discovery and molecular design.
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ABSTRACT
Diabetes mellitus represents one of the most significant and costly health burdens worldwide. Despite major therapeutic advances over the past three decades, substantial unmet needs remain in glycemic durability, β-cell preservation, weight management, metabolic inflammation, lipotoxicity, and long-term cardiovascular and renal protection. This review synthesizes the molecular basis of diabetes pathogenesis, summarizes therapeutic evolution across drug classes, and highlights emerging technologies accelerating target discovery and translational development. Particular emphasis is placed on incretin-based multi-agonists, metabolic-inflammation modulators, β-cell therapeutics, and machine-learning–enabled discovery platforms. More importantly, a new "metabolism-immune-neuroendocrine" integrated therapy framework is proposed for future diabetes intervention. Together, these innovations are reshaping the landscape for the next generation of diabetes therapeutics. -
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REFERENCES
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Liao J., Cong Z., Liu K., et al. (2026). Current diabetes drugs: Lessons learned and implications for next-generation therapeutics. The Innovation Drug Discovery 1:100008. https://doi.org/10.59717/j.xinn-drugdisc.2026.100008
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Liao J., Cong Z., Liu K., et al. (2026). Current diabetes drugs: Lessons learned and implications for next-generation therapeutics. The Innovation Drug Discovery 1:100008. https://doi.org/10.59717/j.xinn-drugdisc.2026.100008
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Figure 1.
Global diabetes epidemiology of T1D and T2D with a significant trend of incidence in younger age
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Figure 2.
Integrated mechanisms underlying insulin resistance
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Figure 3.
β-cell failure and dedifferentiationas a central mechanism in diabetes
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Figure 4.
The Integrated gut-pancreases-liver-muscle-adipocytes-brain axis in glucose homeostasis. The integrated multi-organ network governs systemic glucose homeostasis, linking the gut, brain, pancreas, liver, skeletal muscle, and adipose tissue
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Figure 5.
AI/ML and computational target discovery pipeline
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Figure 6.
Chemical biology and screening innovation stack for diabetes drug discovery
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Figure 7.
Strategies enabling oral delivery of diabetes medicines. Four complementary approaches are implemented to overcome gastrointestinal barriers and enable oral administration of biologic or small-molecule therapies for diabetes
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Figure 8.
Mechanistic framework for quadruple gut-hormone agonists
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Figure 9.
Future tissue-targeted immunometabolic reprogramming strategies
