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Relationship between metformin use and mortality in tuberculosis patients with diabetes: a nationwide cohort study

  • Eunki Chung (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine) ;
  • Dawoon Jeong (Department of Preventive Medicine, Seoul National University College of Medicine) ;
  • Jeongha Mok (Department of Internal Medicine, Pusan National University Hospital, Pusan National University School of Medicine) ;
  • Doosoo Jeon (Department of Internal Medicine, Pusan National University Yangsan Hospital, Pusan National University School of Medicine) ;
  • Hee-Yeon Kang (Department of Cancer Control and Population Health, National Cancer Center Graduate School of Cancer Science and Policy) ;
  • Heejin Kim (Jeju Double Cross Clinic, Korean National Tuberculosis Association) ;
  • Heesun Kim (Department of Health Policy Research, National Evidence-Based Healthcare Collaborating Agency) ;
  • Hongjo Choi (Department of Preventive Medicine, Konyang University College of Medicine) ;
  • Young Ae Kang (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine)
  • Received : 2023.07.18
  • Accepted : 2023.10.23
  • Published : 2024.03.01

Abstract

Background/Aims: To determine whether metformin, which is considered a host-directed therapy for tuberculosis (TB), is effective in improving the prognosis of patients with TB and diabetes mellitus (DM), who have higher mortality than those without DM. Methods: This cohort study included patients who were registered as having TB in the National Tuberculosis Surveillance System. The medical and death records of matched patients were obtained from the National Health Information Database and Statistics Korea, respectively, and data from 2011 to 2017 were collected retrospectively. We classified patients according to metformin use among participants who used diabetes drugs for more than 28 days. The primary outcome was all-cause mortality during TB treatment. Double propensity score adjustment was applied to reduce the effects of confounding and multivariable Cox proportional hazard models were used to estimate adjusted hazard ratio (aHR) with 95% confidence interval (CI). Results: The all-cause mortality rate during TB treatment was lower (9.5% vs. 12.4%, p < 0.01) in the metformin user group. The hazard of death due to all causes after double propensity score adjustment was also lower in the metformin user group (aHR 0.76, 95% CI 0.67-0.86, p < 0.01). There was no significant difference in mortality between metformin users and non-users for TB-related deaths (p = 0.22); however, there was a significant difference in the non-TB-related deaths (p < 0.01). Conclusions: Metformin use in patients with TB-DM co-prevalence is associated with reduced all-cause mortality, suggesting the potential for metformin adjuvant therapy in these patients.

Keywords

Acknowledgement

This work was supported by the National Evidence-Based Healthcare Collaborating Agency, funded by the Ministry of Health and Welfare (NC19-002, NC20-003, and NC21-001) and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea (HI19C1235).

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