Metformin is associated with a lower risk of active tuberculosis in patients with type 2 diabetes
Shang-Yi Lin
Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
School of Medicine, Graduate Institute of Medicine, Sepsis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorHung-Pin Tu
Department of Public Health and Environmental Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorPo-Liang Lu
Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
School of Medicine, Graduate Institute of Medicine, Sepsis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorTun-Chieh Chen
Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorWen-Hung Wang
Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorInn-Wen Chong
Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorCorresponding Author
Yen-Hsu Chen
Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
School of Medicine, Graduate Institute of Medicine, Sepsis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, Hsin Chu, Taiwan
Correspondence: Yen-Hsu Chen, Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 100 Tzyou 1st Road, Kaohsiung City, Taiwan. Email: [email protected]Search for more papers by this authorShang-Yi Lin
Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
School of Medicine, Graduate Institute of Medicine, Sepsis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorHung-Pin Tu
Department of Public Health and Environmental Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorPo-Liang Lu
Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
School of Medicine, Graduate Institute of Medicine, Sepsis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorTun-Chieh Chen
Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorWen-Hung Wang
Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorInn-Wen Chong
Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorCorresponding Author
Yen-Hsu Chen
Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
School of Medicine, Graduate Institute of Medicine, Sepsis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, Hsin Chu, Taiwan
Correspondence: Yen-Hsu Chen, Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 100 Tzyou 1st Road, Kaohsiung City, Taiwan. Email: [email protected]Search for more papers by this authorABSTRACT
Background and objective
Metformin is an oral anti-diabetic therapy (ADT) to manage type 2 diabetes mellitus (T2DM), and has been reported to have potential anti-tuberculosis (TB) effects. This study investigates the risk of active TB among persons with T2DM who were treated with various ADT and insulin therapies.
Methods
We conducted a nationwide population-based cohort study using the Taiwan Longitudinal Health Insurance Database, including 49 028 T2DM patients who were metformin users (n = 44 002) or non-users (n = 5026). A total of 5026 propensity score-matched pairs of metformin users and non-users with T2DM were evaluated from 1998 to 2010. The data were analysed using Cox proportional hazard models.
Results
Patients with T2DM had a significantly higher rate of incident TB than did the control subjects (adjusted hazard ratio: 2.01; 95% confidence interval (95% CI): 1.80–2.25). After adjusting for comorbidities, diabetes complications, ADT type and statin use, metformin use was an independent factor for predicting a reduced risk of active TB (adjusted relative risk (aRR): 0.24; 95% CI: 0.18–0.32). The association between metformin use and active TB risk was also consistent in most subgroup analyses, except for patients with metabolic disorders (aRR: 0.46; 95% CI: 0.11–1.87). This protective effect of metformin was dose-dependent but diminished gradually in the elderly population.
Conclusion
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.
Supporting Information
| Filename | Description |
|---|---|
| resp13338-sup-0001-suppinfo.docxWord 2007 document , 49.7 KB |
Figure S1 Cumulative incidence rate of active TB in patients with and without type 2 diabetes. Table S1 Diabetes complications developed from ICD-9-CM codes. Table S2 Characteristics of the patients with type 2 diabetes and non-type 2 diabetes matched controls. Table S3 Type 2 diabetes was associated with a higher risk of active TB. Table S4 Dose–response relationship between metformin use and TB risk. Table S5 (A) The association between metformin cDDD and age in type 2 diabetes patients with metformin. (B) The association between renal disease and age in type 2 diabetes patients with metformin. Table S6 Characteristics of the metformin users and non-users among type 2 diabetes patients with metabolic disorders. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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