The effect of metformin on culture conversion in tuberculosis patients with diabetes mellitus

Abstract

Background/AimsPatients with diabetes mellitus (DM) and tuberculosis (TB) have increased morbidity and a high risk of treatment failure or recurrence. It is important to manage both diseases simultaneously. Among anti-diabetic drugs, metformin inhibits intracellular growth of mycobacteria. Therefore, we examined the effects of metformin on TB treatment, especially in patients with DM.MethodsThis retrospective cohort study included patients with culture-positive pulmonary TB diagnosed between 2011 and 2012. The primary study outcome was sputum culture conversion after 2 months of treatment.ResultsOf 499 patients diagnosed with culture-positive pulmonary TB, 105 (21%) had DM at diagnosis. Among them, 62 (59.5%) were treated with metformin. Baseline characteristics, except for the presence of chronic renal disease, were not significantly different between the metformin and non-metformin groups. Metformin treatment had no significant effect on sputum culture conversion (p = 0.60) and recurrence within 1 year after TB treatment completion (p = 0.39). However, metformin improved the sputum culture conversion rate in patients with cavitary pulmonary TB, who have higher bacterial loads (odds ratio, 10.8; 95% confidence interval, 1.22 to 95.63).ConclusionsAmong cavitary pulmonary TB patients with DM, metformin can be an effective adjunctive anti-TB agent to improve sputum culture conversion after 2 months of treatment.

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

“…92 Metformin adjunctive treatment however failed to improve sterilizing activity and TB relapsed in mice, with no significant effect being reported for culture conversion rates in diabetes mellitus patients with TB. 134 …”

Therapeutic host-directed strategies to improve outcome in tuberculosis

“…66 Retrospective evaluation of clinical trial data demonstrated that metformin treatment of type-II diabetics with TB is associated with fewer lung cavities, lower proportion of individuals with advanced disease and improved sputum culture conversion rate 2 months post-treatment initiation. 58,64,67 Retrospective analyses also showed that type-II diabetics receiving metformin treatment have a lower TB risk profile compared to those using sulfonylureas. 68 Interestingly, diabetics on metformin treatment have a lower chance of having latent Mtb infection (LTBI), as measured by a positive T-Spot TB test.…”

“…Altogether these effects inhibit Mtb growth, reduce inflammation and prevent lung damage. 58 These findings have promoted metformin as a candidate for therapeutic prevention and adjunctive treatment approaches in TB. 55 In vitro and in vivo murine studies have further shown that metformin treatment reduces inflammation in TB by promoting expansion of anti-inflammatory cell types, particularly alternatively activated macrophages.…”

Medicamentos versátiles: buscando balas mágicas

“…79,80 La metformina se ha planteado como un importante agente adyuvante en el tratamiento de infecciones por micobacterias en pacientes diabéticos y no diabéticos: induce la formación de especies reactivas de oxígeno y nitrógeno en las células infectadas por Mycobacterium tuberculosis, favorece la autofagia de los macrófagos y la síntesis de IFN-γ, lo que induce una respuesta Th1, 81 potencia la acción de los medicamentos antifímicos convencionales, disminuye la carga de bacilos 82 y el tiempo de negativización de cultivos de pacientes con tuberculosis y cavitaciones después de dos meses de tratamiento. 83 La modulación terapéutica de los mecanismos del hospedero para erradicar las infecciones constituye un nuevo paradigma en el descubrimiento de nuevos medicamentos. La respuesta innata contra el complejo Mycobacterium tuberculosis incluye la activación del estallido respiratorio por las especies reactivas de oxígeno (ERO) y nitrógeno (ERN) y la activación de la maquinaria en los fagosomas que promueve la autofagia.…”