Abstract

Chronic diseases such as type 2 diabetes mellitus, benign prostatic hyperplasia (BPH), and autoimmune disorders 
necessitate long-term pharmacotherapy, which can predispose patients to metabolic, hepatic, and immune 
toxicities. This review examines the comparative adverse effects of commonly used therapies across these 
conditions, focusing on systemic and hepatic outcomes. Antidiabetic agents-including metformin, sulfonylureas, 
thiazolidinediones, insulin, GLP-1 receptor agonists, and SGLT2 inhibitors-can induce mitochondrial dysfunction, 
oxidative stress, and rare hepatotoxic events, in addition to metabolic derangements such as weight gain, 
dyslipidemia, and insulin resistance. BPH treatments, particularly alpha-adrenergic blockers and 5-alpha-reductase 
inhibitors, rarely affect liver function but can influence systemic hemodynamics, metabolic balance, and immune 
pathways. Immunomodulatory therapies, including conventional and targeted DMARDs, biologics, and JAK 
inhibitors, carry significant risks of hepatotoxicity, immune suppression, and idiosyncratic drug reactions. Shared 
mechanisms such as oxidative injury, mitochondrial impairment, and cytokine modulation underpin toxicities 
across these diverse drug classes. The review emphasizes the need for vigilant liver function monitoring, 
individualized dosing strategies, pharmacogenomic assessment, and adjunctive interventions targeting oxidative 
stress and metabolic resilience. Understanding these overlapping toxicity patterns is critical for optimizing 
therapeutic efficacy while minimizing systemic and hepatic complications in patients with complex comorbidities.