Effect of anti-tuberculosis drugs on the pharmacokinetics and pharmacodynamics of novel antidiabetic drugs: A scoping review.

BACKGROUND: The co-occurrence of tuberculosis (TB) and diabetes mellitus (DM) presents a growing public global health concern. Managing DM during anti-TB therapy is challenging due to potential drug-drug interactions, especially with rifamycin (RIF).

RESEARCH QUESTION: Assess the effects of anti-TB drugs on the pharmacokinetics and pharmacodynamics of novel antidiabetic agents, including DPP-4 inhibitors (DPP4i), SGLT-2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1a).

STUDY DESIGN AND METHODS: A PRISMA-ScR-based scoping review was conducted among four databases.

RESULTS: Ten studies involving 307 participants were included. RIF significantly reduced the plasma exposure of DPP4i (saxagliptin, gemigliptin, evogliptin) and canagliflozin, while other SGLT2i (dapagliflozin, empagliflozin, ertugliflozin) were minimally affected. No direct data was available for GLP-1a. Adverse events were rare in healthy participants but more frequent in elderly patients with poorly controlled DM. Linezolid and dapagliflozin co-administration may lead to severe pancytopenia.

DISCUSSION: RIF co-administration with gemigliptin, evogliptin and canagliflozin requires caution and potential requiring dose adjustments, while saxagliptin, dapagliflozin, ertugliflozin and empagliflozin appear safer alternatives. Haematologic monitoring is recommended when combining linezolid and dapagliflozin. However, current evidence remains limited by small sample sizes, single-dose designs, inclusion of mainly healthy participants, and lack of data on GLP-1a or other anti-TB agents. The limited inclusion of DM patients with TB, restricted to one study with latent TB infection, further reduces generalisability. We developed a clinical decision algorithm to support co-treatment in TB - DM cases, but further dedicated studies are warranted to guide optimal co-treatment.