Host-Directed Therapy in Tuberculosis: A Systematic Review of Metformin and Vitamin D and Their Potential Synergistic Effects
DOI:
https://doi.org/10.53366/jimki.v12i3.1076Keywords:
Tuberculosis, Host-Directed Therapy, Metformin, Vitamin D, AMPK-mTORAbstract
Introduction: Tuberculosis (TB) remains a major global health problem, challenged by drug resistance and latent infection. Host-Directed Therapy (HDT) has emerged as an adjunctive strategy to enhance TB treatment outcomes by modulating host immune and metabolic responses. Metformin and vitamin D are promising HDT candidates; however, their potential synergistic effects have not been extensively explored.
Method: A narrative literature review was conducted using PubMed, Scopus, Cochrane, Google Scholar, and ProQuest databases, covering publications from January 2015 to August 2025. Relevant studies were identified using the keywords “Tuberculosis,” “Host-Directed Therapy,” “Metformin,” and “Vitamin D.”
Discussion: Metformin contributes to TB control through activation of the AMP-activated protein kinase (AMPK) pathway, promoting autophagy and suppressing inflammation, although clinical benefits vary depending on metabolic status and dosage. Vitamin D enhances innate immunity by inducing antimicrobial peptides and promoting phagocyte maturation, with more consistent clinical effects observed in patients with vitamin D deficiency. Preclinical evidence suggests a potential synergistic effect of metformin and vitamin D via regulation of the AMPK–mTOR pathway; however, direct clinical evidence remains limited.
Conclusion: Metformin and vitamin D show potential as HDT-based adjunctive therapies for TB, but well-designed controlled clinical trials are required to determine the efficacy and safety of their combined use.
Keywords: Tuberculosis; Host-Directed Therapy; Metformin; Vitamin D, AMPK-mTOR
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