TY - JOUR
T1 - Metformin Use Reverses the Increased Mortality Associated with Diabetes Mellitus during Tuberculosis Treatment
AU - Degner, Nicholas R.
AU - Wang, Jann Yuan
AU - Golub, Jonathan E.
AU - Karakousis, Petros C.
N1 - Publisher Copyright:
© The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
PY - 2018/1/15
Y1 - 2018/1/15
N2 - Background The global type 2 diabetes mellitus (DM) epidemic threatens progress made in reducing tuberculosis (TB)-related mortality worldwide. Previous clinical studies have not fully evaluated potential confounding variables in addressing the impact of DM on TB treatment outcomes. The antidiabetic agent metformin regulates autophagy and may play a role as a host-directed therapeutic adjuvant to antitubercular treatment. Methods We conducted a retrospective cohort study comprising patients aged ≥13 years undergoing treatment for culture-confirmed, drug-susceptible pulmonary TB. We assessed the effect of DM on mortality during TB treatment and 2-month TB sputum-culture conversion. We also evaluated the effect of metformin use on survival during TB treatment. Results Among 2416 patients undergoing TB treatment, after adjusting for age, sex, chronic kidney disease, cancer, hepatitis C, tobacco use, cavitary disease, and treatment adherence, patients with DM had 1.91 times higher odds (95% confidence interval [CI], 1.51-2.40) of death during TB treatment than patients without DM, and 1.72 (95% CI, 1.25-2.38) times higher odds of remaining culture-positive at 2 months. Metformin use in patients with DM was significantly associated with decreased mortality during TB treatment (hazard ratio, 0.56 [95% CI,.39-.82]), and metformin users had similar mortality as patients without DM. Conclusions This study suggests that despite multiple potential confounding variables, DM poses an increased risk of adverse TB treatment outcomes. There was a significant association between metformin use and decreased mortality during TB treatment, suggesting a potential role for this agent as adjunctive, host-directed therapy.
AB - Background The global type 2 diabetes mellitus (DM) epidemic threatens progress made in reducing tuberculosis (TB)-related mortality worldwide. Previous clinical studies have not fully evaluated potential confounding variables in addressing the impact of DM on TB treatment outcomes. The antidiabetic agent metformin regulates autophagy and may play a role as a host-directed therapeutic adjuvant to antitubercular treatment. Methods We conducted a retrospective cohort study comprising patients aged ≥13 years undergoing treatment for culture-confirmed, drug-susceptible pulmonary TB. We assessed the effect of DM on mortality during TB treatment and 2-month TB sputum-culture conversion. We also evaluated the effect of metformin use on survival during TB treatment. Results Among 2416 patients undergoing TB treatment, after adjusting for age, sex, chronic kidney disease, cancer, hepatitis C, tobacco use, cavitary disease, and treatment adherence, patients with DM had 1.91 times higher odds (95% confidence interval [CI], 1.51-2.40) of death during TB treatment than patients without DM, and 1.72 (95% CI, 1.25-2.38) times higher odds of remaining culture-positive at 2 months. Metformin use in patients with DM was significantly associated with decreased mortality during TB treatment (hazard ratio, 0.56 [95% CI,.39-.82]), and metformin users had similar mortality as patients without DM. Conclusions This study suggests that despite multiple potential confounding variables, DM poses an increased risk of adverse TB treatment outcomes. There was a significant association between metformin use and decreased mortality during TB treatment, suggesting a potential role for this agent as adjunctive, host-directed therapy.
KW - diabetes mellitus
KW - host-directed therapy
KW - metformin
KW - treatment outcomes
KW - tuberculosis
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U2 - 10.1093/cid/cix819
DO - 10.1093/cid/cix819
M3 - Article
C2 - 29325084
AN - SCOPUS:85040626121
SN - 1058-4838
VL - 66
SP - 198
EP - 205
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 2
ER -