A Systematic Review on the Effect of Diabetes Mellitus on the Pharmacokinetics of Tuberculosis Drugs

Objectives The coexistence of TB and DM (TB-DM) has been associated with an increased risk of treatment failure, death, delayed culture conversion and drug resistance. As plasma concentrations may influence clinical outcomes, we evaluated the evidence on the PK of TB drugs in DM individuals to guide management. Methods We performed a systematic review and meta-analysis through searches of major databases from 1946 to 6 July 2023. PROSPERO (CRD42022323566). Results Out of 4173 potentially relevant articles, we identified 16 studies assessing rifampicin PK, 9 on isoniazid, 8 on pyrazinamide and 3 on ethambutol. Two studies reported on second line anti-TB drugs. According to our analysis, RIF Tmax was significantly prolonged in patients with DM compared to non-DM patients. We found no significant differences for RIF C max , AUC 0-24 or C2hr, INH C2hr, PZA C2hr, PZA T max and ETB T max . While RIF C2hr was slightly reduced in TB-DM patients, this finding was not statistically significant. Conclusions This review comprehensively examines the impact of DM on the PK of TB drugs. We observed significant heterogeneity among studies. Given the association between lower plasma concentrations and poor clinical outcomes among DM patients, we recommend a higher dose limit to correct for larger bodyweight of patients with DM.