Abstract
BACKGROUND: Khat (Catha edulis), a psychoactive plant commonly chewed in Ethiopia, is known to influence drug metabolism through its active compound, cathinone. Among patients with T2DM, concurrent khat chewing and OAD use may result in pharmacokinetic and pharmacodynamic interactions, particularly in polypharmacy contexts. Despite these concerns, the clinical relevance of khat-OAD interactions remains poorly understood in high-prevalence, low-resource settings. METHODS: This study assessed the prevalence, predictors, and perceptions of potential khat-OAD interactions among T2DM patients. A convergent parallel mixed-methods design was employed from July 1 to December 30, 2024, at Gondar University Hospital, Ethiopia. A total of 422 adult T2DM patients on OAD therapy who reported khat use were systematically sampled. Quantitative data on demographics, clinical profiles, medication use, and khat chewing behaviors were collected through structured interviews and verified via medical records. Potential interactions were identified using drug interaction databases, and logistic regression was used to determine independent predictors. Additionally, in-depth interviews with 20 patients and healthcare providers explored awareness, perceptions, and clinical experiences related to khat use and diabetes care. RESULTS: Among the 422 participants, 63.3% (n = 267) had at least one potential khat-OAD interaction, and 23.2% (n = 98) experienced a major interaction. The most frequently implicated drugs were glibenclamide and sitagliptin. Significant predictors of interaction included female sex (AOR = 1.38; 95% CI: 1.00-1.89), polypharmacy with ≥ 7 medications (AOR = 2.43; 95% CI: 1.61-3.67), daily khat use (AOR = 2.20; 95% CI: 1.52-3.18), and khat use for ≥ 13 years (AOR = 1.09; 95% CI: 1.04-1.15). Qualitative findings highlighted the widespread cultural normalization of khat chewing, low patient awareness of potential interactions, and gaps in provider counseling. CONCLUSIONS: Harmful khat-OAD interactions are common among T2DM patients in Northwest Ethiopia, primarily driven by behavioral and treatment-related factors, highlighting the need for culturally sensitive pharmacovigilance and patient education. CLINICAL TRIAL NUMBER: Not applicable.