Dose-Dependent Toxicity
Adverse effects that increase in frequency or severity as the drug dose increases, reflecting a predictable relationship between drug exposure and toxicity. Gastrointestinal side effects of GLP-1 receptor agonists are dose-dependent, which is why gradual dose titration is used.
Technical Context
Dose-dependent (Type A) adverse effects are predictable extensions of the drug's pharmacology and typically affect a larger proportion of patients at higher doses. They are the most common type of ADR, accounting for approximately 80% of all adverse drug reactions. For GLP-1 RAs, gastrointestinal effects (nausea, vomiting, diarrhoea) are dose-dependent — incidence increases at each dose escalation step and is highest at the maximum therapeutic dose. This dose-dependency is the rationale for gradual dose titration. Dose-dependent toxicity is characterised during dose escalation studies (Phase I) and dose-ranging studies (Phase II). Management includes dose reduction, temporary dose interruption, or slower titration schedule. In contrast, dose-independent (Type B) reactions (allergic, idiosyncratic) can occur at any dose.