Evidence map›Metformin × all-cause mortality›PMID 31623569›Full record

SynthesisBMC infectious diseases2019

Impact of metformin on the risk and treatment outcomes of tuberculosis in diabetics: a systematic review.

Xinyu Yu, Ling Li, Liangtao Xia, Xin Feng, Fan Chen, Shiyi Cao, Xiang Wei

Registry-linked trialOpen access · goldFull text readMeta-AnalysisSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in BMC infectious diseases, 2019. The graph read 10 numbers from its abstract, feeding 7 cells of the map: it supports the treatment in 2, finds no clear difference in 1. It also reports 2 associations that do not count as treatment evidence, such as OR 0.47 (0.27 to 0.83) for all-cause mortality. It is linked to trial NCT05215990 (Efficacy of Metformin for Sputum Conversion in Patients With Active Pulmonary Tuberculosis), which is not on this map. Cited by 35 papers, 1 of them a synthesis that pooled it.

10numbers the graph read from it
6cells of the map it votes in
35citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

Ratios

← favours the treatmentfavours the comparator →
0.250.51 · no effect
All-cause mortalityfavours the treatment · against placebo · t2dfeeds one cell of the map
OR 0.470.27 to 0.83
Abbreviations: TB, tuberculosis; LTBI, latent tuberculosis infection; n, number of cases; N, number of participants; CI, confidence interval; OR, odds ratio; SD, standard deviation The impact of metformin on treatment outcomes of TB disease According to the combined analyses (see Fig. 3 ), the TB mortality could be limited by metformin usage (OR, 0.47; 95%CI, 0.27 to 0.83), and the sputum culture conversion at 2 months of TB disease was significantly promoted in metformin users compared to non-users (OR, 2.72; 95%CI, 1.11 to 6.69).
FeedsMetformin×all-cause mortality
All-cause mortalityfavours the treatment · against placebo · t2dfeeds one cell of the map
OR 0.470.27 to 0.83
Abbreviations: TB, tuberculosis; LTBI, latent tuberculosis infection; n, number of cases; N, number of participants; CI, confidence interval; OR, odds ratio; SD, standard deviation The impact of metformin on treatment outcomes of TB disease According to the combined analyses (see Fig. 3 ), the TB mortality could be limited by metformin usage (OR, 0.47; 95%CI, 0.27 to 0.83), and the sputum culture conversion at 2 months of TB disease was significantly promoted in metformin users compared to non-users (OR, 2.72; 95%CI, 1.11 to 6.69).
FeedsMetformin×all-cause mortality
Glycemic controlfavours the treatment · head-to-head · t2dfeeds 2 cells of the map
RR 0.240.18 to 0.32
Participants without metformin usage 329 Adjusted RR: 0.24 (95%CI, 0.18 to 0.32) Unadjusted RR: 0.37 (95%CI, 0.29 to 0.47) The duration of DM diagnosis, comorbidities (chronic pulmonary disease/ renal disease), oral anti-diabetic therapy, and insulin injection therapy Ma et al. 2018 [ 21 ] (China) Retrospective cohort study Culture-positive retreatment pulmonary TB patients with type 2 DM Multidrug-resistant TB, extensively drug-resistant TB, and extra-pulmonary TB were excluded.( n  = 58) Metformin treatment in regimens for diabetes (1) Success treatment of TB (2) Sputum culture conversion by the end of 2 months (3) Relapse rates of patients Patients without metformin medication 58 There were a higher proportion of treatment success (OR, 6.00; 95%CI, 0.71 to 50.59) and sputum culture conversions by the end of 2 months (OR, 2.80; 95%CI, 0.55 to 14.23) among metformin group.
FeedsMetformin×glycemic controlOther glucose-lowering×glycemic control
Blood pressurefavours the treatment · head-to-head · t2dfeeds 2 cells of the map
RR 0.340.17 to 0.67
Patients aged < 20 years or had a diagnosis of TB were excluded.( n  = 9475) Participants received ≥60 cumulative defined daily dose of metformin and < 15 cumulative defined daily dose of sulfonylurea TB occurrence (ICD-9, 010-018) Participants received ≥60 cumulative defined daily dose of sulfonylurea and < 15 cumulative defined daily dose of metformin 263 Adjusted RR: 0.337 (95%CI, 0.169 to 0.673) Unadjusted RR: 0.477 (95%CI, 0.268 to 0.850) Age, sex, adapted diabetes complication severity index score, index year, income level, and comorbidities Tseng et al. 2018 [ 7 ] (Taiwan) Retrospective cohort study Newly diagnosed diabetes patients (ICD-9) who had been followed up in the outpatient clinics with a prescription of antidiabetic drugs for two or more times ( n  = 164,267) Patients had been prescribed metformin as the first antidiabetic drug Incidence density of TB infection Patients without metformin prescriptions 2336 Adjusted HR: 0.552 (95%CI, 0.493-0.617) Unadjusted HR: NA Age, diabetes duration, sex, occupation, living region, hypertension, dyslipidemia, obesity, diabetes-related complications, antidiabetic drugs and so on Abbreviations: TB Tuberculosis, LTBI Latent tu
FeedsMetformin×blood pressureOther glucose-lowering×blood pressure

Differences

← favours the treatmentfavours the comparator →
-3.706.400 · no effect
Adverse events & safetyno clear difference · against placebo · t2dfeeds one cell of the map
Δ 1.40-3.70 to 6.40
Fig. 1 Study screening flowchart Table 1 Characteristics of included studies in the systematic review Study Authors and Published Year (location) Study Design Participants Exposure Outcomes Controls Case Result Adjustment of covariates Magee et al. 2018 [ 8 ] (U.S.A.) Cross-sectional study Patients with diabetes identified by self-report and glycated hemoglobin ( n  = 4958) Metformin medication identified by self-report A diagnosis of LTBI infection identified by QuantiFERON-TB Gold In-tube Patients without metformin medication 575 Latent TB infection prevalence was non-significantly higher in those without metformin use (prevalence difference, 1.4, 95%CI, -3.7 -6.4%) compared to those self-reporting any metformin use (OR, 1.1, 95%CI, 0.7 to 1.9).
FeedsMetformin×adverse events & safety

Read, but not usablea number the graph found but could not read as for or against

All-cause mortalityan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
OR 0.470.27 to 0.83
Metformin medication during the anti-tuberculosis treatment is significantly associated with a smaller TB mortality (OR, 0.47; 95%CI, 0.27 to 0.83), and a higher probability of sputum culture conversion at 2 months of TB disease (OR, 2.72; 95%CI, 1.11 to 6.69) among patients with diabetes.
FeedsMetformin×all-cause mortality
All-cause mortalitycomparator not stated · t2dfeeds one cell of the map
OR 0.290.14 to 0.95
The Mortality was 3% among patients who received metformin compared to 10% among patients in the non-metformin group (OR, 0.29; 95%CI, 0.14 to 0.95).
FeedsMetformin×all-cause mortality
Pharmacokinetics & dosingdirection of benefit for this outcome is not defined · head-to-head · t2dfeeds one cell of the map
HR 0.840.74 to 0.96
Diabetics do not satisfy the exposure criteria 1514 Adjusted HR: 0.84 (95%CI, 0.74 to 0.96) TB risk was lower in high-dose metformin users than in low-dose users (HR, 0.83; 95%CI, 0.72 to 0.97) Sex, type 1 diabetes mellitus, age, low income, chronic obstructive pulmonary disease, liver cirrhosis, pulmonary cancer, extra-pulmonary cancer, bronchiectasis, and so on Lin et al. 2018 [ 10 ] (Tai Wan) Retrospective cohort study Patients who were 20-100 years old and who were newly diagnosed with type 2 DM (ICD-9-CM, 250.X0 and 250.X2) ( n  = 10,052) Metformin usage A diagnosis of active TB (ICD-9-CM, 010-018) during the follow-up period and the prescription of more than two anti-TB medications for more than 90 days.
FeedsMetformin×pharmacokinetics & dosing
All-cause mortalitydirection of benefit for this outcome is not defined · head-to-head · t2dfeeds one cell of the map
OR 10.81.22 to 95.6
Metformin improved the sputum culture conversion rate in patients with cavitary pulmonary TB (OR, 10.8; 95%CI, 1.22 to 95.63) Sex, statin use, insulin, cancer, AFB smear grade, and drug resistance Lin et al. 2017 [ 20 ] (Tai Wan) Retrospective cohort study Patients aged 20 and older newly diagnosed with diabetes (ICD-9250.XX and A-code A181) and without a past history of pulmonary TB ( n  = 22,256) Metformin treatment Incidence of pulmonary TB identified in follow-up Patients without metformin treatment 682 Unadjusted crude HR: 0.42 (95%CI, 0.35 to 0.50) Adjusted HR: 0.52 (95%CI, 0.43 to 0.62) Sex, age, alcoholism, chronic obstructive pulmonary disease, cirrhosis, alcoholic liver damage, hepatitis C, chronic kidney diseases, and malignancies Degner et al. 2018 [ 12 ] (Tai Wan) Retrospective cohort study Patients aged ≥13 years with culture-confirmed, drug-susceptible pulmonary TB undergoing treatment and diabetes ( n  = 634) Metformin medication within 30 days of starting TB treatment Effect on mortality among patients with DM undergoing TB treatment Patients without metformin prescriptions 634 Adjusted HR: 0.56 (95%CI, 0.39 to 0.82) Unadjusted HR: 0.50 (95%CI, 0.35 to 0.72) Age
FeedsMetformin×all-cause mortality
All-cause mortalityan association or prognostic statement, not a treatment comparison · t2dfeeds one cell of the map
OR 2.721.11 to 6.69
Metformin medication during the anti-tuberculosis treatment is significantly associated with a smaller TB mortality (OR, 0.47; 95%CI, 0.27 to 0.83), and a higher probability of sputum culture conversion at 2 months of TB disease (OR, 2.72; 95%CI, 1.11 to 6.69) among patients with diabetes.
FeedsMetformin×all-cause mortality

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

Metformin×all-cause mortality

SupportsOpen on the map →What to test next →

1 readable study in this cell: 0 favour the treatment, 1 find no difference, 0 favour the comparator.

Belief with this paper
0.25no deciding trial · 0 families support, 0 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect
NCT000387272,779 enrolled · 1996
HR 0.990.79 to 1.25

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

Metformin×adverse events & safety

InconclusiveOpen on the map →What to test next →

22 readable studies in this cell: 9 favour the treatment, 8 find no difference, 5 favour the comparator.

Belief with this paper
0.27contested · 4 families support, 11 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT017190031,413 enrolled · 2012
Adjusted mean -0.72-0.95 to -0.48
NCT018093271,186 enrolled · 2013
Δ -0.40-0.59 to -0.21
NCT022730501,136 enrolled · 2014
Δ -8.90-13.3 to -4.50
NCT01126580807 enrolled · 2010
Δ -0.22-0.36 to -0.08
NCT01023581784 enrolled · 2009
Δ -0.67-0.96 to -0.37
NCT00386100688 enrolled · 2006
Δ 1.47-14.8 to 20.8
NCT01217073685 enrolled · 2010
Δ 1.00-9.80 to 13.1
NCT01890122647 enrolled · 2013
Δ -0.68-0.89 to -0.47
NCT00727857600 enrolled · 2007
Δ 0.860.51 to 1.22
NCT01958671461 enrolled · 2013
Δ -2.60-13.1 to 8.10
NCT00328172302 enrolled · 2006
Δ -0.85-1.10 to -0.59
NCT01485614200 enrolled · 2012
Δ 2.40-10.0 to 14.9

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

Metformin×glycemic control

No readable resultOpen on the map →What to test next →

40 readable studies in this cell: 42 favour the treatment, 12 find no difference, 7 favour the comparator.

Belief with this paper
0.84replicated · 32 families support, 6 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT017190031,413 enrolled · 2012
Adjusted mean -0.72-0.95 to -0.48
NCT018093271,186 enrolled · 2013
Δ -0.40-0.59 to -0.21
NCT022730501,136 enrolled · 2014
Δ -0.89-1.08 to -0.69
NCT008598981,093 enrolled · 2009
Δ -0.53-0.74 to -0.32
The study to understand the genetics of the acute response to metformi…PMID 25812009 · 1,033 enrolled · 2008
Δ -0.85-43.8 to 26.7
NCT00643851994 enrolled · 2008
Δ -0.86-1.11 to -0.62
NCT01708902876 enrolled · 2012
Δ -1.00-1.23 to -0.78
NCT00676338820 enrolled · 2008
Δ -0.05-0.26 to 0.17
NCT01126580807 enrolled · 2010
Δ -0.22-0.36 to -0.08
NCT01023581784 enrolled · 2009
Δ -0.67-0.96 to -0.37
NCT01076088744 enrolled · 2010
Δ -0.84-1.15 to -0.52
NCT00386100688 enrolled · 2006
Δ -0.49-0.67 to -0.30

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

Metformin×blood pressure

No readable resultOpen on the map →What to test next →

6 readable studies in this cell: 2 favour the treatment, 3 find no difference, 1 favour the comparator.

Belief with this paper
0.40contested · 1 family supports, 1 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT00676338820 enrolled · 2008
Δ 0.36-1.02 to 1.73
Metformin may adversely affect orthostatic blood pressure recovery in …PMID 32979921 · 2020
increase 1.300.30 to 2.60
Metformin reduces arterial stiffness and improves endothelial function…PMID 19996308 · 2010
Δ -3.50
Does metformin decrease blood pressure in patients with Type 2 diabete…PMID 15975107 · 2005
Δ 1.50
Bexagliflozin as an adjunct to metformin for the treatment of type 2 d…PMID 37409573 · 2023
Δ -7.07-9.83 to -4.32

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

Other glucose-lowering×glycemic control

No readable resultOpen on the map →What to test next →

8 readable studies in this cell: 5 favour the treatment, 0 find no difference, 3 favour the comparator.

Belief with this paper
0.50contested · 3 families support, 1 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT017093055,570 enrolled · 2012
Δ 0.190.02 to 0.36
NCT050350821,018 enrolled · 2021
Δ -0.24-0.44 to -0.04
The efficacy and safety of imeglimin as add-on therapy in patients wit…PMID 23160726 · 2013
placebo-subtracted decrease -0.44
A prospective, parallel group, open-labeled, comparative, multi-centri…PMID 21510461 · 2010
decrease -19.4
One-year acarbose treatment raises fasting serum acetate in diabetic p…PMID 7743764 · 1995
increase -1.00
Dorzagliatin add-on therapy to metformin in patients with type 2 diabe…PMID 35551292 · 2022
Δ -0.66-0.79 to -0.53
Miglitol combined with metformin improves glycaemic control in type 2 …PMID 11703422 · 2001
treatment effect 0.22
Baseline glucagon impacts glucose-lowering effects of acarbose but not…PMID 40319921 · 2025
Δ -1.32

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

Other glucose-lowering×blood pressure

SupportsOpen on the map →What to test next →

No other readable study in this cell yet. This paper is the evidence.

Belief with this paperNo claim has been compiled for this cell yet.

Metformin×pharmacokinetics & dosing

No readable resultOpen on the map →What to test next →

2 readable studies in this cell: 0 favour the treatment, 2 find no difference, 0 favour the comparator.

Belief with this paper
0.25no deciding trial · 0 families support, 0 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT00631488146 enrolled · 2008
Δ 22.6-0.60 to 45.8
NCT0200488674 enrolled · 2006
Δ -6.60-34.0 to 20.8

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

4 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05215990 phase1 / phase2unknown statusnot on this mapstarted 2022, after this paper: background citation

Efficacy of Metformin for Sputum Conversion in Patients With Active Pulmonary Tuberculosis: A Randomized Controlled Trial

TypeinterventionalSponsorMahidol UniversityRan2022 to 2023Enrolled80ConditionsTuberculosis, PulmonaryArmsMetFORMIN 500 Mg Oral Tablet, Placebo
5 · Its place in the literature

Who cites it

35 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.

  1. Pooled it
  2. Impact of Diabetes Mellitus in Tuberculosis (TB) Patients on TB Transmission.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Anti-TB Drugs for Drug-Sensitive and Drug-ResistantCurrent issues in molecular biology · 2025
    Review
  9. Article
  10. Article
  11. Article
  12. Host-directed therapy for tuberculosis.European journal of medical research · 2025
    Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article
6 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

7 · Who and what money

Authors and funding

7 authors at 4 institutions in 2 countries.

Xinyu YuDivision of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, China.
Ling LiDepartment of Infectious Diseases, Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Liangtao XiaDivision of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, China.
Xin FengDivision of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, China.
Fan ChenSchool of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No. 13 Hangkong Road, Wuhan, 430030, China.
Shiyi CaoSchool of Public Health, Tongji Medical College, Huazhong University of Science and Technology, No. 13 Hangkong Road, Wuhan, 430030, China. caoshiyi@hust.edu.cn.ORCID http://orcid.org/0000-0002-6338-9696
Xiang WeiDivision of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, China. xiangwei@tjh.tjmu.edu.cn.
Tongji Hospital · CNHuazhong University of Science and Technology · CNMinistry of Education of the People's Republic of China · CNUnion Hospital · CN

Funding

National Natural Science Foundation of China 71603091
8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

backgroundTuberculosis (TB) remains one of the infectious diseases with a leading cause of death among adults worldwide. Metformin, a first-line medication for the treatment of type 2 diabetes, may have potential for treating TB. The aims of the present systematic review were to evaluate the impact of metformin prescription on the risk of tuberculosis diseases, the risk of latent TB infection (LTBI) and treatment outcomes of tuberculosis among patients with diabetic mellitus.

methodsDatabases were searched through March 2019. Observational studies reporting the effect of metformin prescription on the risk and treatment outcomes of TB were included in the systematic review. We qualitatively analyzed results of included studies, and then pooled estimate effects with 95% confidence intervals (CIs) of different outcome using random-effect meta-analyses.

resultsThis systematic review included 6980 cases from 12 observational studies. The meta-analysis suggested that metformin prescription could decrease the risk of TB among diabetics (pooled odds ratio [OR], 0.38; 95%CI, 0.21 to 0.66). Metformin prescription was not related to a lower risk of LTBI (OR, 0.73; 95%CI, 0.30 to 1.79) in patients with diabetes. Metformin medication during the anti-tuberculosis treatment is significantly associated with a smaller TB mortality (OR, 0.47; 95%CI, 0.27 to 0.83), and a higher probability of sputum culture conversion at 2 months of TB disease (OR, 2.72; 95%CI, 1.11 to 6.69) among patients with diabetes. The relapse of TB was not statistically reduced by metformin prescription (OR, 0.55; 95%CI, 0.04 to 8.25) in diabetics.

conclusionsAccording to current observational evidence, metformin prescription significantly reduced the risk of TB in patients with diabetes mellitus. Treatment outcomes of TB disease could also be improved by the metformin medication among diabetics.

Indexed as

Antitubercular AgentsDiabetes Mellitus, Type 2HumansHypoglycemic AgentsMetforminOdds RatioRisk FactorsSputumTreatment OutcomeTuberculosisAntitubercular AgentsHypoglycemic AgentsMetforminMeta-analysisMetforminTuberculosis

Identifiers

PMID31623569
PMCPMC6796338
OpenAlexW2980829712

What OpenQuestion holds

Textfull text, public
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.