Metformin is associated with a lower risk of active tuberculosis in patients with type 2 diabetes

Lin, Shang‐Yi; Tu, Hung-Pin; Lu, Po‐Liang; Chen, Tun‐Chieh; Wang, Wen Hung; Chong, Inn‐Wen; Chen, Yen-Hsu

doi:10.1111/resp.13338

Cited by 31 publications

(38 citation statements)

References 32 publications

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“…The complex interactions among oxidative stress, mitochondrial dysfunction and immunological dysfunction may contribute to the development of TB in the geriatric population and worsen the disease outcomes, especially in presence of co‐morbid conditions such as smoking and diabetes mellitus. In a 1:1 propensity score‐matched analysis of data from a longitudinal health insurance database in Taiwan, Lin et al showed 76% reduction in TB risk among 5026 diabetic patients put on metformin as compared with 5026 non‐metformin users, after adjusting for co‐morbidities, diabetic complications, anti‐diabetic therapy type and statin use . In another longitudinal study from the same locality, metformin users were associated with 44% reduction in mortality during TB treatment despite their higher haemoglobin A1c level.…”

Section: Tuberculosismentioning

confidence: 99%

Contemporary Concise Review 2018: Respiratory infections and tuberculosis

Hui

Leung

2019

Respirology

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Section: Tuberculosismentioning

confidence: 99%

Contemporary Concise Review 2018: Respiratory infections and tuberculosis

Hui

Leung

2019

Respirology

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“…Of these, 12 were further excluded because two of them did not treat statin use as the exposure, six did not report tuberculosis infection as the outcome, one study did not provide available outcome data, and the other three were abstracts of already included studies. Finally, nine observational studies were included (10)(11)(12)(13)(14)(15)(16)(17)(18).…”

Section: Literature Searchmentioning

confidence: 99%

“…These studies were published between 2014 and 2019, and all of them included Asian people. Regarding the study design, five studies were retrospective cohort studies (10,(15)(16)(17)(18), one was a prospective cohort study (11), two were nested case-control studies (12,14), and another one was a retrospective case-control study (13).…”

Section: Study Characteristics and Quality Evaluationmentioning

confidence: 99%

“…Moreover, statins may also synergistically increase the treatment efficacy of antituberculosis, such as rifampin (9). However, an early cohort study did not show a significant association between statin use and tuberculosis infection (10), while subsequent studies indicated that use of statins may be associated with reduced tuberculosis infection (11)(12)(13)(14)(15)(16)(17)(18). The potential reasons for the inconsistencies of the above findings remain unknown.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Statin Use May Be Associated With Reduced Active Tuberculosis Infection: A Meta-Analysis of Observational Studies

Li¹,

Sheng²,

Lou³

2020

Front. Med.

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Background: Tuberculosis remains one of the leading causes of mortality among the infectious diseases, while statins were suggested to confer anti-infective efficacy in experimental studies. We aimed to evaluate the association between statin use and tuberculosis infection in a meta-analysis. Method: Relevant studies were obtained via systematically search of PubMed and Embase databases. A random or a fixed effect model was applied to pool the results according to the heterogeneity among the included studies. Subgroup analyses according to the gender and diabetic status of the participants were performed. We assessed the quality of evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: Nine observational studies were included. Significant heterogeneity was detected among the studies (p for Cochrane's Q test < 0.001, I 2 = 93%). The GRADE approach showed generally low quality of evidence. Pooled results showed that statin use was associated with reduced active tuberculosis infection (risk ratio [RR]: 0.60, 95% confidence interval [CI]: 0.45 to 0.75, p < 0.001). Subgroup analyses showed that the negative association between statin use and active tuberculosis infection was consistent in men (RR: 0.63, p = 0.01) and women (RR: 0.58, p < 0.001), in participants with (RR: 0.63, p = 0.02) and without diabetes (RR: 0.50, p < 0.001), in retrospective cohort studies (RR: 0.56, p = 0.02), prospective cohort studies (RR: 0.76, p = 0.03), nested case-controls studies (RR: 0.57, p < 0.001), and case-control studies (RR: 0.60, p < 0.001), and in studies with statin used defined as any use within 1 year (RR: 0.59, p < 0.001) or during follow-up (RR: 0.61, p < 0.001). Significant publication bias was detected (p for Egger's regression test = 0.046). Subsequent "trim and fill" analyses retrieved an unpublished study to generate symmetrical funnel plots, and meta-analysis incorporating this study did not significantly affect the results (RR: 0.72, 95% CI: 0.68 to 0.76, p < 0.001). Conclusions: Statin use may be associated with reduced active tuberculosis infection. Randomized controlled trials (RCTs) are needed to confirm the potential preventative role of statin use on tuberculosis infection.

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“…While in one case metformin enhanced the activity of isoniazid and ethionamide [25], in another one it did not improve the efficacy of the combined first-line drugs [26]. Recent retrospective studies reported a protective effect for metformin against reactivation of latent TB in diabetic patients [27][28][29]. Phase II clinical trials have been initiated ( Table 1).…”

Section: Metforminmentioning

confidence: 99%

Host-Directed Therapies and Anti-Virulence Compounds to Address Anti-Microbial Resistant Tuberculosis Infection

2020

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Despite global efforts to contain tuberculosis (TB), the disease remains a leading cause of morbidity and mortality worldwide, further exacerbated by the increased resistance to antibiotics displayed by the tubercle bacillus Mycobacterium tuberculosis. In order to treat drug-resistant TB, alternative or complementary approaches to standard anti-TB regimens are being explored. An area of active research is represented by host-directed therapies which aim to modulate the host immune response by mitigating inflammation and by promoting the antimicrobial activity of immune cells. Additionally, compounds that reduce the virulence of M. tuberculosis, for instance by targeting the major virulence factor ESX-1, are being given increased attention by the TB research community. This review article summarizes the current state of the art in the development of these emerging therapies against TB.

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Metformin is associated with a lower risk of active tuberculosis in patients with type 2 diabetes

Abstract: Among all types of ADT and insulin therapies, metformin is the only agent with a decreased risk of active TB in the T2DM population. However, this effect was diminished in the elderly population and was not observed in patients with metabolic disorders.

Cited by 31 publications

References 32 publications

Contemporary Concise Review 2018: Respiratory infections and tuberculosis

Contemporary Concise Review 2018: Respiratory infections and tuberculosis

Statin Use May Be Associated With Reduced Active Tuberculosis Infection: A Meta-Analysis of Observational Studies

Host-Directed Therapies and Anti-Virulence Compounds to Address Anti-Microbial Resistant Tuberculosis Infection

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