Publications

Hyperglycaemia, a defining feature of diabetes mellitus and metabolic syndrome, exerts profound and multifaceted effects on drug metabolism, pharmacokinetics, and toxicity. These effects stem from coordinated disruptions in metabolic pathways, redox homeostasis, immune function, mitochondrial biology, and organ physiology. As global diabetes prevalence continues to rise, the overlap between chronic hyperglycaemia and therapeutic exposure has become a growing challenge in clinical pharmacology and toxicology. This review synthesizes systems-level insights into how hyperglycaemia modulates drug absorption, distribution, metabolism, and excretion (ADME), and how these changes modify susceptibility to adverse drug reactions (ADRs). We examine the cellular and molecular mechanisms through which elevated glucose alters enzymatic activity, transporter function, oxidative stress responses, inflammatory tone, and xenobiotic biotransformation. Organ-specific vulnerabilities in the liver, kidney, cardiovascular system, and immune system are explored, alongside emerging evidence from pharmacogenomics and exposomics. We also discuss the implications for dose optimization, therapeutic monitoring, drug–disease interactions, and precision medicine. A systems biology perspective reveals that hyperglycaemia not only modifies individual metabolic pathways but reconfigures entire regulatory networks, reshaping the toxicity landscape for numerous drug classes. Understanding these complex interactions is essential for improving drug safety, reducing treatment failures, and designing next-generation therapeutics for populations affected by chronic metabolic disease.