Shifting the Paradigm in Global Diabetes Management: Beyond Glycohemoglobinism and Toward Etiological Mitigation via Minimizing Insulin Resistance on the Basis of Pharmacogenetics
Review highlights the necessity of targeting insulin resistance through pharmacogenetics in type 2 diabetes, suggesting a shift from symptom management to genotype-directed therapy.
Key Points
To advocate for shifting type 2 diabetes management away from glycemic biomarker reduction toward addressing root-cause insulin resistance through pharmacogenetic frameworks.
Critically analyzed current clinical reliance on glycated hemoglobin (HbA1c) reduction as a primary endpoint in type 2 diabetes care.
Synthesized the pharmacogenomic determinants and mechanisms across major antidiabetic drug classes, including metformin, sulfonylureas, SGLT2 inhibitors, GLP-1 agonists, and thiazolidinediones.
Characterized persistent hyperglycemia as a late-stage biomarker of systemic insulin resistance rather than the primary disease etiology.
Identified that patient-specific genetic variations regulate antidiabetic drug metabolism and insulin receptor kinetics, supporting a transition toward precision, genotype-directed therapeutic strategies.