Prospective, Open Labelled, Randomised, Parallel Group Study To Evaluate The Efficacy And Safety Of Metformin Add- On Therapy To Standard ATT In Newly Diagnosed Pulmonary Tuberculosis Patients
Authors/Creators
- 1. Associate Professor, Department of Pulmonary Medicine, Katihar Medical College and Hospital, Katihar, Bihar, India
- 2. Assistant Professor, Department of Pharmacology, Darbhanga Medical College and Hospital, Laheriasarai,Darbhanga, Bihar, India
Description
Aim: Clinical Evaluation of Efficacy and Safety of Metformin add- on Therapy to Standard ATT in Newly Diagnosed Pulmonary Tuberculosis Patients. Methods: This was a prospective, open labelled, randomised, parallel group study conducted in KMCH,Katihar, Bihar in Department of Pulmonary Medicine for 1 year. involving 100 tuberculosis patients. Patients were screened and those who fulfilled the selection criteria were included in the study. Patients were randomly allocated to either of the two groups – Control group and Metformin group with 50 patients in each group. In control group, patients received only standard ATT and in Metformin group, patients received Metformin 250 mg twice daily along with standard ATT. Results: The mean age of the patients in control group was 44 (±11.8) years and in Metformin group, it was 40.3 (±11.1) years. In control group, there were 35 males and 15 females and in Metformin group, 33 males and 17 females. There was no significant difference seen in age and gender distribution of the patients between two groups, as evidenced by the p value more than in unpaired t test for age and chi square test for gender. The average time taken for sputum smear conversion was significantly lower in the Metformin group in comparison with the control group (p = 0.011, unpaired t-test). It was about 3.5 (±1.64) weeks in Metformin group while it was 4.8 (±2.21) weeks in the control group. All the subjects enrolled in the study were non-diabetics. At the time of enrollment, their fasting and post prandial blood sugar and HbA1c values were measured and only those who were having normal values were selected for the study. The mean fasting blood sugar was 96.5±8.8mg/dl and 92.2±11.4mg/dl and the mean sugar values at post prandial state was 127.22±24.15 mg/dl and 125.98±30.11 mg/dl in control and Metformin groups respectively at the time of enrollment. In control group, the baseline HbA1c was 4.82±0.41 % and it was 4.95±0.63 % in Metformin group. Adverse events were seen in 5 patients (10%) in control group and 7 patients (14%) in Metformin group. The difference was not statistically significant (p value = 0.81, chi square test). All of the adverse events were only minor in nature and gastrointestinal related problems like nausea, vomiting and gastritis. Conclusion: It was observed that the average time taken for sputum smear conversion was 3.5 weeks in Metformin group and 4.8 weeks in control group. There were no serious adverse events and most of the adverse events were gastrointestinal related and minor in nature.
Abstract (English)
Aim: Clinical Evaluation of Efficacy and Safety of Metformin add- on Therapy to Standard ATT in Newly Diagnosed Pulmonary Tuberculosis Patients. Methods: This was a prospective, open labelled, randomised, parallel group study conducted in KMCH,Katihar, Bihar in Department of Pulmonary Medicine for 1 year. involving 100 tuberculosis patients. Patients were screened and those who fulfilled the selection criteria were included in the study. Patients were randomly allocated to either of the two groups – Control group and Metformin group with 50 patients in each group. In control group, patients received only standard ATT and in Metformin group, patients received Metformin 250 mg twice daily along with standard ATT. Results: The mean age of the patients in control group was 44 (±11.8) years and in Metformin group, it was 40.3 (±11.1) years. In control group, there were 35 males and 15 females and in Metformin group, 33 males and 17 females. There was no significant difference seen in age and gender distribution of the patients between two groups, as evidenced by the p value more than in unpaired t test for age and chi square test for gender. The average time taken for sputum smear conversion was significantly lower in the Metformin group in comparison with the control group (p = 0.011, unpaired t-test). It was about 3.5 (±1.64) weeks in Metformin group while it was 4.8 (±2.21) weeks in the control group. All the subjects enrolled in the study were non-diabetics. At the time of enrollment, their fasting and post prandial blood sugar and HbA1c values were measured and only those who were having normal values were selected for the study. The mean fasting blood sugar was 96.5±8.8mg/dl and 92.2±11.4mg/dl and the mean sugar values at post prandial state was 127.22±24.15 mg/dl and 125.98±30.11 mg/dl in control and Metformin groups respectively at the time of enrollment. In control group, the baseline HbA1c was 4.82±0.41 % and it was 4.95±0.63 % in Metformin group. Adverse events were seen in 5 patients (10%) in control group and 7 patients (14%) in Metformin group. The difference was not statistically significant (p value = 0.81, chi square test). All of the adverse events were only minor in nature and gastrointestinal related problems like nausea, vomiting and gastritis. Conclusion: It was observed that the average time taken for sputum smear conversion was 3.5 weeks in Metformin group and 4.8 weeks in control group. There were no serious adverse events and most of the adverse events were gastrointestinal related and minor in nature.
Files
IJTPR,Vol12,Issue1,Article1.pdf
Files
(177.0 kB)
| Name | Size | Download all |
|---|---|---|
|
md5:17358e9c733b76604208fb9ef2298610
|
177.0 kB | Preview Download |
Additional details
Dates
- Accepted
-
2021-12-22
Software
References
- 1. World Health Organization: Global Tuberculosis Programme. A Framework for Effective Tuberculosis Control. WHO/TB/94.179. Geneva, Switzerland: WHO; 1994. 2. World Health Organization: global tuberculosis report 2020. 2020. 3. Abouzeid MS, Al RF, Memish ZA. Mortality among tuberculosis patients in Saudi Arabia (2001–2010). Ann Saudi Med. 2013;33 (3):247-52. 4. Zheng Z, Lin J, Lu Z, et al. Mortality risk in the population of HIV-positive individuals in Southern China: a cohort study. PLoS One. 2019;14(2):e0210856– e0210856. 5. Henegar C, Behets F, Vanden Driessche K, et al. Mortality among tuberculosis patients in the Democratic Republic of Congo. Int J Tuberc Lung Dis. 2012;16(9):1199-1204. 6. Aljadani R, Ahmed AE, Al-Jahdali H. Tuberculosis mortality and associated factors at King Abdulaziz Medical City Hospital. BMC Infect Dis. 2019;19(1):427. 7. Karthika M, Philip S, Prathibha MT, Varghese A, Rakesh PS. Why are people dying due to tuberculosis? A study from Alappuzha District, Kerala, India. Indian J Tuberc. 2019;66(4):443-47. 8. Lin CH, Lin CJ, Kuo YW, et al. Tuberculosis mortality: patient characteristics and causes. BMC Infect Dis. 2014;14(1):5. 9. Romanowski K, Baumann B, Basham CA, Ahmad Khan F, Fox GJ, Johnston JC. Long-term all-cause mortality in people treated for tuberculosis: a systematic review and meta-analysis. Lancet Infect Dis. 2019;19(10):1129-37. 10. Pedrazzoli D, Kranzer K, Thomas HL, Lalor MK. Trends and risk factors for death and excess all-cause mortality among notified tuberculosis patients in the UK: an analysis of surveillance data. ERJ Open Res. 2019;5(4):4. 11. Bris tol Myers Squibb Company. GLUCOPHAGE®(metformin hydrochloride) tablets and GLUCOPHAGE® XR (metformin hydrochloride) extended-release tablets prescribing information. 12. Singla R, Bharty SK, Gupta UA, Khayyam KU, Vohra V, Singla N, Myneedu VP, Behera D. Sputum smear positivity at two months in previously untreated pulmonary tuberculosis patients. International journal of mycobacteriology. 2013; 2(4):199-205. 13. Kim J, Kwak N, Lee HY, Kim TS, Kim CK, Han SK, Yim JJ. Effect of drug resistance on negative conversion of sputum culture in patients with pulmonary tuberculosis. International Journal of Infectious Diseases. 2016; 42:64-8 14. Ekinci GH, Karakaya E, Ongel EA, Haciomeroglu O, Yilmaz A. Patient and doctor delays in smear-negative and smear-positive pulmonary tuberculosis patients attending a referral hospital in Istanbul, Turkey. The Scientific World Journal. (2014). 15. Parikh R, Nataraj G, Kanade S, Khatri V, Mehta P. Time to sputum conversion in smear positive pulmonary TB patients on category I DOTS and factors delaying it. J Assoc Physicians India. 2012; 60(22):6 16. Singhal A, Jie L, Kumar P, Hong GS, Leow MK, Paleja B, Tsenova L, Kurepina N, Chen J, Zolezzi F, Kreiswirth B. Metformin as adjunct antituberculosis therapy. Science translational medicine. 2014; 6(263):263ra159- . 17. Lee YJ, Han SK, Park JH, Lee JK, Kim DK, Chung HS, Heo EY. The effect of metformin on culture conversion in tuberculosis patients with diabetes mellitus. The Korean journal of internal medicine. 2018; 33(5):933 . 18. Ma Y, Pang Y, Shu W, Liu YH, Ge QP, Du J, Li L, Gao WW. Metformin reduces the relapse rate of tuberculosis patients with diabetes mellitus: experiences from 3-year follow-up. European Journal of Clinical Microbiology & Infectious Diseases. 2018;37(7):1259-63 . 19. Zhang Y, Yew WW, Barer MR. Targeting persisters for tuberculosis control. Antimicrobial agents and chemotherapy. 2012; 56(5):2223-30. 20. Bento CF, Empadinhas N, Mendes V. Autophagy in the fight against tuberculosis. DNA and cell biology. 2015; 34(4):228-42 21. Singh A, Prasad R, Balasubramanian V, Gupta N, Gupta P. Prevalence of adverse drug reaction with first-line drugs among patients treated for pulmonary tuberculosis. Clinical Epidemiology and Global Health. 2015; 3: S80-90 . 22. Diabetes Prevention Program Research Group. Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study. Diabetes care. 2012; 35(4):731-7.