The role of metformin in tuberculosis control among TB and diabetes mellitus comorbid individuals

Abstract

Tuberculosis (TB) is a major global health concern, and its control is particularly hindered in patients with comorbidities such as type 2 diabetes mellitus (TBDM). Metformin, a commonly prescribed antidiabetic medication, has gained attention because of its potential role in improving TB treatment outcomes in patients with TBDM. This review aims to assess the role of metformin in TB case management among TBDM comorbid individuals. By reviewing the available literature, we aimed to explore the potential benefits, complications, mechanisms, and considerations surrounding metformin use as an adjunctive therapy for TB treatment. The findings of this review will shed light on current understanding and highlight areas for further investigation.

Keywords: Mycobacterium tuberculosis; TB-diabetes patients; diabetes; host-directed therapeutics; immunomodulatory; metformin.

FIGURE 1

Antidiabetic and antimicrobial effects of metformin. The absorption of metformin into hepatocytes and muscle cells leads to the activation of AMPK, which reduces fatty acid synthesis and gluconeogenesis in the liver while enhancing glucose uptake in muscle cells (Szymczak-Pajor et al., 2022). Activated AMPK inhibits NF-κB and mTOR which leads to reduced inflammation and an increase in autophagy respectively. Also, metformin reduces intestinal glucose absorption, increases insulin sensitivity, and reduces ROS production. AMPK, adenosine monophosphate-activated protein kinase; SREPB-1, sterol-regulatory-element-binding-protein-1; CBP & CRTC2, creb binding protein and creb-regulated transcription coactivator 2, mTOR, mammalian target of rapamycin, NF-κB, nuclear factor kappa-B; ROS, reactive oxygen species; SGLT 1, sodium-glucose cotransporter 1; GLUT 4, glucose transporter type 4.

FIGURE 2

Clinical outcomes among TB/TBDM patients on metformin and anti-TB drugs, and those only on anti-TB drugs. Observational retrospective studies have demonstrated that adding metformin to standard anti-TB therapy offers significant benefits for patients with TB and diabetes mellitus (DM). Compared to those receiving only anti-TB drugs, patients on metformin exhibit reduced mortality, treatment failure, and relapse rates, alongside faster sputum culture and smear-microscopy conversion due to metformin’s ability to inhibit intracellular Mycobacterium tuberculosis (Mtb) growth (Degner et al., 2018; Naicker et al., 2020; Singhal et al., 2014). Additionally, metformin accelerates lung cavity resolution on chest X-rays and improves glycemic control, addressing key challenges in TB-DM management (Singhal et al., 2014).