The Effect of Diabetes Mellitus on the Pharmacokinetics of Tuberculosis Drugs

While pharmacokinetics (PK) of many drugs is known to be altered in individuals with diabetes mellitus (DM), the effects of DM on the PK of anti-tuberculosis (TB) drugs remains poorly understood. We performed a systematic review through searches of major databases from 1946 to 6 July 2023. The literature search identified 4173 potentially relevant articles. After reviewing the eligibility criteria, 21 articles were included that assessed the PK of anti-TB drugs among patients with DM. Most articles focused on first line TB drugs; we identified 16 studies assessing rifampicin PK, 9 studies on isoniazid, 8 on pyrazinamide and 3 assessing ethambutol. Only 2 studies reported on second line anti-TB treatment. While some studies showed lower plasma concentrations of TB medications among DM patients, this finding was not consistent. In addition, we observed high variability in findings and significant heterogeneity among studies in terms of study design and differences in demographics. This review provides detailed overview of the limited evidence available regarding the PK of anti-TB medications in patients with DM. However, due to significant heterogeneity between studies, no conclusions could be made. Adequately designed PK studies using standardise methodologies are urgently needed to make recommendations regarding drug dosing in patients affected both by TB and DM. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Chief Scientist Office (CAF/20/03) and British Infection Association (Grant/2022/SPG/MC) received by MC. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: We used published data openly available. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors