Metabolic and neurological warning phenotypes during tirzepatide treatment: a clinical pharmacology and pharmacovigilance review

This preprint presents a structured clinical pharmacology and pharmacovigilance review of metabolic and neurological warning phenotypes during tirzepatide treatment. It integrates regulatory information, randomised human studies, controlled physiology, pharmacovigilance analyses, and case reports to examine hypoglycaemia, altered counterregulation, ketosis and ketoacidosis, hyponatraemia, volume disturbance, thiamine deficiency, loss of physical reserve, and product-quality hazards. The review distinguishes established pharmacological effects from case-level associations and mechanistic hypotheses, and proposes a practical framework based on contemporaneous glucose, sodium–osmolality, ketone/acid-base, renal, nutritional, and product-provenance assessment. This is a structured narrative review and does not provide a pooled meta-analytic estimate.