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39 metformin COVID-19 controlled studies, 1 RCTs
27% improvement
for early treatment, RR
0.73
[0.28-1.94]
https://c19early.com/mfmeta.html
0
0.5
1
1.5+
All studies
27%
39
118,536
Improvement, Studies, Patients
Relative Risk
Mortality
33%
31
74,262
Ventilation
37%
5
1,371
ICU admission
10%
3
29,616
Hospitalization
20%
8
24,275
Progression
28%
5
3,719
Recovery
38%
2
4,008
Cases
4%
5
27,298
Viral clearance
1%
1
418
RCTs
27%
1
418
Peer-reviewed
26%
37
96,337
Prophylaxis
26%
37
117,930
Early
27%
1
418
Late
97%
1
188
Metformin for COVID-19
c19early.com/mf May 2022
Favors metformin
Favors control
after exclusions
• Statistically significant improvements are seen for
mortality ,
ventilation , and
hospitalization . 23 studies from 22 independent teams in 8 different countries show statistically significant
improvements in isolation (20 for the most serious outcome).
• Results are robust — in exclusion sensitivity analysis 27 of 39
studies must be excluded to avoid finding statistically significant efficacy
in pooled analysis.
0
0.5
1
1.5+
All studies
27%
39
118,536
Improvement, Studies, Patients
Relative Risk
Mortality
33%
31
74,262
Ventilation
37%
5
1,371
ICU admission
10%
3
29,616
Hospitalization
20%
8
24,275
Progression
28%
5
3,719
Recovery
38%
2
4,008
Cases
4%
5
27,298
Viral clearance
1%
1
418
RCTs
27%
1
418
Peer-reviewed
26%
37
96,337
Prophylaxis
26%
37
117,930
Early
27%
1
418
Late
97%
1
188
Metformin for COVID-19
c19early.com/mf May 2022
Favors metformin
Favors control
after exclusions
• Most studies analyze existing use with diabetic patients. Many
results are subject to confounding by indication — metformin is
typically used early in the progression of type 2 diabetes. Prophylaxis
results typically include continuing use after infection and
hospitalization, and greater benefit is seen for more serious outcomes.
The beneficial effect of metformin may be more related to later stages of
COVID-19. The
TOGETHER RCT shows
27% lower mortality. While not statistically significant,
p = 0.53, this
is consistent with the mortality results from
all studies ,
33%
[25‑40%] .
• While many treatments have some level
of efficacy, they do not replace vaccines and other measures to avoid
infection.
None of the metformin studies show zero events in the treatment arm.
Multiple treatments are typically used
in combination, and
other treatments
are more effective.
• No treatment, vaccine, or intervention is 100%
available and effective for all variants. All practical, effective, and safe
means should be used.
Denying the efficacy of treatments increases mortality, morbidity, collateral
damage, and endemic risk.
• All data to reproduce this paper and
sources are in the
appendix .
Other meta analyses for metformin can be found in
[Hariyanto , Kow , Lukito , Yang ] , showing significant improvements for mortality and progression.
Highlights
We show traditional outcome specific analyses and combined
evidence from all studies, incorporating treatment delay, a primary
confounding factor in COVID-19 studies.
A
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Reis (DB RCT)
27%
0.73 [0.28-1.94]
death
7/215
9/203
Improvement, RR [CI]
Treatment
Control
Tau2 = 0.00, I2 = 0.0%, p = 0.54
Early treatment
27%
0.73 [0.28-1.94]
7/215
9/203
27% improvement
Tamura
97%
0.03 [0.00-0.58]
death
115 (n)
73 (n)
Improvement, RR [CI]
Treatment
Control
Tau2 = 0.00, I2 = 0.0%, p = 0.019
Late treatment
97%
0.03 [0.00-0.58]
0/115
0/73
97% improvement
Luo
75%
0.25 [0.07-0.84]
death
3/104
22/179
Improvement, RR [CI]
Treatment
Control
Wang
58%
0.42 [0.01-1.98]
death
1/9
13/49
Chen
33%
0.67 [0.20-1.78]
death
4/43
15/77
Kim
64%
0.36 [0.10-1.23]
death
113 (n)
122 (n)
Li
78%
0.22 [0.09-0.54]
death
2/37
21/94
Goodall
3%
0.97 [0.75-1.25]
death
74/210
280/771
Gao
-225%
3.25 [1.03-7.41]
progression
16/56
4/54
Pérez-Belm.. (PSM)
-10%
1.10 [0.84-1.40]
death
79/249
79/249
Bramante
7%
0.93 [0.81-1.06]
death
394/2,333
791/3,923
Lalau (PSM)
22%
0.78 [0.55-1.10]
death
671 (n)
419 (n)
Huh
-1%
1.01 [0.75-1.37]
progression
104/272
774/2,533
Crouse
61%
0.39 [0.16-0.87]
death
8/76
34/144
Lally
52%
0.48 [0.28-0.84]
death
16/127
144/648
Oh
-26%
1.26 [0.81-1.95]
death
5,946 (n)
5,946 (n)
Wargny
28%
0.72 [0.53-0.95]
death
247/1,553
330/1,241
Holt
-27%
1.27 [0.72-2.22]
cases
12/429
434/14,798
Khunti
23%
0.77 [0.73-0.81]
death
population-based cohort
Jiang (PSM)
46%
0.54 [0.13-2.26]
death
3/74
10/74
Ghany
66%
0.34 [0.19-0.59]
death
392 (n)
747 (n)
Alamgir
27%
0.73 [0.63-0.84]
death
11,062 (n)
11,062 (n)
Ravindra
30%
0.70 [0.28-1.56]
death
5/53
57/313
Blanc
79%
0.21 [0.03-1.46]
death
1/14
25/75
Boye
10%
0.90 [0.86-0.94]
hosp.
2,067/4,250
3,196/5,281
Cheng (PSM)
-65%
1.65 [0.71-3.86]
death
678 (n)
535 (n)
Wang
12%
0.88 [0.81-0.97]
ICU
6,504 (n)
10,000 (n)
Ando
39%
0.61 [0.38-0.99]
hosp.
Wander
15%
0.85 [0.80-0.90]
death
Saygili (PSM)
42%
0.58 [0.37-0.92]
death
120 (n)
120 (n)
Ong
47%
0.53 [0.31-0.87]
death
33/186
57/169
Bliden
60%
0.40 [0.12-1.37]
death
3/34
9/41
Al-Salameh
55%
0.45 [0.17-0.94]
death/ICU
9/47
22/50
Wallace (PSW)
72%
0.28 [0.21-0.37]
death
103/1,203
1,536/6,970
Ojeda-Ferná.. (PSM)
16%
0.84 [0.79-0.89]
death
1,476/6,556
1,787/6,556
Usman
60%
0.40 [0.12-1.37]
death
3/34
9/41
Wong
51%
0.49 [0.43-0.57]
death
Wong (PSW)
59%
0.41 [0.22-0.80]
death
786 (n)
428 (n)
MacFadden
1%
0.99 [0.96-1.01]
cases
n/a
n/a
Tau2 = 0.03, I2 = 92.0%, p < 0.0001
Prophylaxis
26%
0.74 [0.68-0.80]
4,663/44,221
9,649/73,709
26% improvement
All studies
27%
0.73 [0.67-0.80]
4,670/44,551
9,658/73,985
27% improvement
39 metformin COVID-19 studies
c19early.com/mf May 2022
Tau2 = 0.03, I2 = 91.6%, p < 0.0001
Effect extraction pre-specified (most serious outcome, see appendix)
Favors metformin
Favors control
B
C
Figure 1. A. Random effects
meta-analysis. This plot shows pooled effects, discussion can be found in the heterogeneity section,
and results for specific outcomes can be found in the individual outcome analyses.
Effect extraction is pre-specified, using the most serious outcome reported.
For details of effect extraction see the
appendix .
B. Scatter plot showing the
distribution of effects reported in studies.
C. History of all reported
effects (chronological within treatment stages).
Introduction
We analyze all significant studies
concerning the use of
metformin
for COVID-19.
Search methods, inclusion criteria, effect
extraction criteria (more serious outcomes have priority), all individual
study data, PRISMA answers, and statistical methods are detailed in
Appendix 1 . We present random effects meta-analysis results for all
studies, for studies within each treatment stage, for individual outcomes, for
peer-reviewed studies, for Randomized Controlled Trials (RCTs), and after
exclusions.
Figure 2 shows stages of possible treatment for
COVID-19.
Prophylaxis refers to regularly taking medication before
becoming sick, in order to prevent or minimize infection.
Early
Treatment refers to treatment immediately or soon after symptoms appear,
while
Late Treatment refers to more delayed treatment.
Preclinical Research
An
In Vitro study supports the efficacy of metformin
[Parthasarathy ] .
Preclinical research is an important part of the development of
treatments, however results may be very different in clinical trials.
Preclinical results are not used in this paper.
Results
Figure 3 shows a visual overview of the results, with details in
Table 1 and
Table 2 .
Figure
4 ,
5 ,
6 ,
7 ,
8 ,
9 ,
10 ,
11 ,
12 , and
13
show forest plots for a random effects meta-analysis of
all studies with pooled effects, mortality results, ventilation, ICU admission, hospitalization, progression, recovery, cases, viral clearance, and peer reviewed studies.
0
0.5
1
1.5+
ALL STUDIES
MORTALITY
VENTILATION
ICU ADMISSION
HOSPITALIZATION
PROGRESSION
RECOVERY
CASES
VIRAL CLEARANCE
RANDOMIZED CONTROLLED TRIALS
PEER-REVIEWED
After Exclusions
ALL STUDIES
All
Prophylaxis
Early
Late
Metformin for COVID-19
C19EARLY.COM/MF MAY 2022
Treatment time Number of studies reporting positive effects
Total number of studies Percentage of studies reporting positive effects
Random effects meta-analysis results
Early treatment
1
1
100%
27% improvement
RR 0.73 [0.28‑1.94]
p = 0.54
Late treatment
1
1
100%
97% improvement
RR 0.03 [0.00‑0.58]
p = 0.019
Prophylaxis
31
37
83.8%
26% improvement
RR 0.74 [0.68‑0.80]
p < 0.0001
All studies
33
39
84.6%
27% improvement
RR 0.73 [0.67‑0.80]
p < 0.0001
Table 1. Results by treatment stage.
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Reis (DB RCT)
27%
0.73 [0.28-1.94]
death
7/215
9/203
Improvement, RR [CI]
Treatment
Control
Tau2 = 0.00, I2 = 0.0%, p = 0.54
Early treatment
27%
0.73 [0.28-1.94]
7/215
9/203
27% improvement
Tamura
97%
0.03 [0.00-0.58]
death
115 (n)
73 (n)
Improvement, RR [CI]
Treatment
Control
Tau2 = 0.00, I2 = 0.0%, p = 0.019
Late treatment
97%
0.03 [0.00-0.58]
0/115
0/73
97% improvement
Luo
75%
0.25 [0.07-0.84]
death
3/104
22/179
Improvement, RR [CI]
Treatment
Control
Wang
58%
0.42 [0.01-1.98]
death
1/9
13/49
Chen
33%
0.67 [0.20-1.78]
death
4/43
15/77
Kim
64%
0.36 [0.10-1.23]
death
113 (n)
122 (n)
Li
78%
0.22 [0.09-0.54]
death
2/37
21/94
Goodall
3%
0.97 [0.75-1.25]
death
74/210
280/771
Gao
-225%
3.25 [1.03-7.41]
progression
16/56
4/54
Pérez-Belm.. (PSM)
-10%
1.10 [0.84-1.40]
death
79/249
79/249
Bramante
7%
0.93 [0.81-1.06]
death
394/2,333
791/3,923
Lalau (PSM)
22%
0.78 [0.55-1.10]
death
671 (n)
419 (n)
Huh
-1%
1.01 [0.75-1.37]
progression
104/272
774/2,533
Crouse
61%
0.39 [0.16-0.87]
death
8/76
34/144
Lally
52%
0.48 [0.28-0.84]
death
16/127
144/648
Oh
-26%
1.26 [0.81-1.95]
death
5,946 (n)
5,946 (n)
Wargny
28%
0.72 [0.53-0.95]
death
247/1,553
330/1,241
Holt
-27%
1.27 [0.72-2.22]
cases
12/429
434/14,798
Khunti
23%
0.77 [0.73-0.81]
death
population-based cohort
Jiang (PSM)
46%
0.54 [0.13-2.26]
death
3/74
10/74
Ghany
66%
0.34 [0.19-0.59]
death
392 (n)
747 (n)
Alamgir
27%
0.73 [0.63-0.84]
death
11,062 (n)
11,062 (n)
Ravindra
30%
0.70 [0.28-1.56]
death
5/53
57/313
Blanc
79%
0.21 [0.03-1.46]
death
1/14
25/75
Boye
10%
0.90 [0.86-0.94]
hosp.
2,067/4,250
3,196/5,281
Cheng (PSM)
-65%
1.65 [0.71-3.86]
death
678 (n)
535 (n)
Wang
12%
0.88 [0.81-0.97]
ICU
6,504 (n)
10,000 (n)
Ando
39%
0.61 [0.38-0.99]
hosp.
Wander
15%
0.85 [0.80-0.90]
death
Saygili (PSM)
42%
0.58 [0.37-0.92]
death
120 (n)
120 (n)
Ong
47%
0.53 [0.31-0.87]
death
33/186
57/169
Bliden
60%
0.40 [0.12-1.37]
death
3/34
9/41
Al-Salameh
55%
0.45 [0.17-0.94]
death/ICU
9/47
22/50
Wallace (PSW)
72%
0.28 [0.21-0.37]
death
103/1,203
1,536/6,970
Ojeda-Ferná.. (PSM)
16%
0.84 [0.79-0.89]
death
1,476/6,556
1,787/6,556
Usman
60%
0.40 [0.12-1.37]
death
3/34
9/41
Wong
51%
0.49 [0.43-0.57]
death
Wong (PSW)
59%
0.41 [0.22-0.80]
death
786 (n)
428 (n)
MacFadden
1%
0.99 [0.96-1.01]
cases
n/a
n/a
Tau2 = 0.03, I2 = 92.0%, p < 0.0001
Prophylaxis
26%
0.74 [0.68-0.80]
4,663/44,221
9,649/73,709
26% improvement
All studies
27%
0.73 [0.67-0.80]
4,670/44,551
9,658/73,985
27% improvement
39 metformin COVID-19 studies
c19early.com/mf May 2022
Tau2 = 0.03, I2 = 91.6%, p < 0.0001
Effect extraction pre-specified (most serious outcome, see appendix)
Favors metformin
Favors control
Figure 4. Random effects meta-analysis for all studies with pooled effects.
This plot shows pooled effects, discussion can be found in the heterogeneity section,
and results for specific outcomes can be found in the individual outcome analyses.
Effect extraction is pre-specified, using the most serious outcome reported.
For details of effect extraction see the
appendix .
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Reis (DB RCT)
27%
0.73 [0.28-1.94]
7/215
9/203
Improvement, RR [CI]
Treatment
Control
Tau2 = 0.00, I2 = 0.0%, p = 0.54
Early treatment
27%
0.73 [0.28-1.94]
7/215
9/203
27% improvement
Tamura
97%
0.03 [0.00-0.58]
115 (n)
73 (n)
Improvement, RR [CI]
Treatment
Control
Tau2 = 0.00, I2 = 0.0%, p = 0.019
Late treatment
97%
0.03 [0.00-0.58]
0/115
0/73
97% improvement
Luo
75%
0.25 [0.07-0.84]
3/104
22/179
Improvement, RR [CI]
Treatment
Control
Wang
58%
0.42 [0.01-1.98]
1/9
13/49
Chen
33%
0.67 [0.20-1.78]
4/43
15/77
Kim
64%
0.36 [0.10-1.23]
113 (n)
122 (n)
Li
78%
0.22 [0.09-0.54]
2/37
21/94
Goodall
3%
0.97 [0.75-1.25]
74/210
280/771
Pérez-Belm.. (PSM)
-10%
1.10 [0.84-1.40]
79/249
79/249
Bramante
7%
0.93 [0.81-1.06]
394/2,333
791/3,923
Lalau (PSM)
22%
0.78 [0.55-1.10]
671 (n)
419 (n)
Crouse
61%
0.39 [0.16-0.87]
8/76
34/144
Lally
52%
0.48 [0.28-0.84]
16/127
144/648
Oh
-26%
1.26 [0.81-1.95]
5,946 (n)
5,946 (n)
Wargny
28%
0.72 [0.53-0.95]
247/1,553
330/1,241
Khunti
23%
0.77 [0.73-0.81]
population-based cohort
Jiang (PSM)
46%
0.54 [0.13-2.26]
3/74
10/74
Ghany
66%
0.34 [0.19-0.59]
392 (n)
747 (n)
Alamgir
27%
0.73 [0.63-0.84]
11,062 (n)
11,062 (n)
Ravindra
30%
0.70 [0.28-1.56]
5/53
57/313
Blanc
79%
0.21 [0.03-1.46]
1/14
25/75
Cheng (PSM)
-65%
1.65 [0.71-3.86]
678 (n)
535 (n)
Wander
15%
0.85 [0.80-0.90]
Saygili (PSM)
42%
0.58 [0.37-0.92]
120 (n)
120 (n)
Ong
47%
0.53 [0.31-0.87]
33/186
57/169
Bliden
60%
0.40 [0.12-1.37]
3/34
9/41
Wallace (PSW)
72%
0.28 [0.21-0.37]
103/1,203
1,536/6,970
Ojeda-Ferná.. (PSM)
16%
0.84 [0.79-0.89]
1,476/6,556
1,787/6,556
Usman
60%
0.40 [0.12-1.37]
3/34
9/41
Wong
51%
0.49 [0.43-0.57]
Wong (PSW)
59%
0.41 [0.22-0.80]
786 (n)
428 (n)
Tau2 = 0.04, I2 = 88.2%, p < 0.0001
Prophylaxis
33%
0.67 [0.60-0.75]
2,455/32,663
5,219/40,993
33% improvement
All studies
33%
0.67 [0.60-0.75]
2,462/32,993
5,228/41,269
33% improvement
31 metformin COVID-19 mortality results
c19early.com/mf May 2022
Tau2 = 0.04, I2 = 87.6%, p < 0.0001
Favors metformin
Favors control
Figure 5. Random effects meta-analysis for mortality results.
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Li
-27%
1.27 [0.12-13.6]
1/37
2/94
Improvement, RR [CI]
Treatment
Control
Lalau (PSM)
7%
0.93 [0.64-1.35]
671 (n)
419 (n)
Bliden
76%
0.24 [0.06-1.03]
2/34
10/41
Usman
76%
0.24 [0.06-1.03]
2/34
10/41
Wong
41%
0.59 [0.52-0.66]
Tau2 = 0.08, I2 = 54.7%, p = 0.023
Prophylaxis
37%
0.63 [0.42-0.94]
5/776
22/595
37% improvement
All studies
37%
0.63 [0.42-0.94]
5/776
22/595
37% improvement
5 metformin COVID-19 mechanical ventilation results
c19early.com/mf May 2022
Tau2 = 0.08, I2 = 54.7%, p = 0.023
Favors metformin
Favors control
Figure 6. Random effects meta-analysis for ventilation.
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Wang
12%
0.88 [0.81-0.97]
6,504 (n)
10,000 (n)
Improvement, RR [CI]
Treatment
Control
Wander
2%
0.98 [0.92-1.06]
Ojeda-Ferná.. (PSM)
22%
0.78 [0.64-0.95]
166/6,556
212/6,556
Tau2 = 0.01, I2 = 70.4%, p = 0.065
Prophylaxis
10%
0.90 [0.80-1.01]
166/13,060
212/16,556
10% improvement
All studies
10%
0.90 [0.80-1.01]
166/13,060
212/16,556
10% improvement
3 metformin COVID-19 ICU results
c19early.com/mf May 2022
Tau2 = 0.01, I2 = 70.4%, p = 0.065
Favors metformin
Favors control
Figure 7. Random effects meta-analysis for ICU admission.
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Reis (DB RCT)
6%
0.94 [0.55-1.61]
hosp.
24/215
24/203
Improvement, RR [CI]
Treatment
Control
Tau2 = 0.00, I2 = 0.0%, p = 0.84
Early treatment
6%
0.94 [0.55-1.61]
24/215
24/203
6% improvement
Ghany
29%
0.71 [0.52-0.86]
hosp.
392 (n)
747 (n)
Improvement, RR [CI]
Treatment
Control
Boye
10%
0.90 [0.86-0.94]
hosp.
2,067/4,250
3,196/5,281
Ando
39%
0.61 [0.38-0.99]
hosp.
Wander
3%
0.97 [0.94-1.01]
hosp.
Ojeda-Ferná.. (PSM)
3%
0.97 [0.94-1.00]
hosp.
3,551/6,556
3,670/6,556
Usman
34%
0.66 [0.39-1.13]
hosp. time
34 (n)
41 (n)
Wong
40%
0.60 [0.57-0.63]
hosp.
Tau2 = 0.04, I2 = 98.0%, p = 0.005
Prophylaxis
21%
0.79 [0.68-0.93]
5,618/11,232
6,866/12,625
21% improvement
All studies
20%
0.80 [0.69-0.94]
5,642/11,447
6,890/12,828
20% improvement
8 metformin COVID-19 hospitalization results
c19early.com/mf May 2022
Tau2 = 0.04, I2 = 97.6%, p = 0.0055
Favors metformin
Favors control
Figure 8. Random effects meta-analysis for hospitalization.
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Reis (DB RCT)
31%
0.69 [0.28-1.68]
8/216
11/205
Improvement, RR [CI]
Treatment
Control
Tau2 = 0.00, I2 = 0.0%, p = 0.42
Early treatment
31%
0.69 [0.28-1.68]
8/216
11/205
31% improvement
Kim
52%
0.48 [0.19-1.24]
113 (n)
122 (n)
Improvement, RR [CI]
Treatment
Control
Gao
-225%
3.25 [1.03-7.41]
16/56
4/54
Huh
-1%
1.01 [0.75-1.37]
104/272
774/2,533
Jiang (PSM)
80%
0.20 [0.05-0.77]
8/74
17/74
Tau2 = 0.77, I2 = 87.3%, p = 0.53
Prophylaxis
27%
0.73 [0.29-1.89]
128/515
795/2,783
27% improvement
All studies
28%
0.72 [0.34-1.53]
136/731
806/2,988
28% improvement
5 metformin COVID-19 progression results
c19early.com/mf May 2022
Tau2 = 0.57, I2 = 83.4%, p = 0.41
Favors metformin
Favors control
Figure 9. Random effects meta-analysis for progression.
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Wargny
15%
0.85 [0.74-0.97]
no disch.
690/1,553
702/1,241
Improvement, RR [CI]
Treatment
Control
Wong (PSW)
61%
0.39 [0.21-0.75]
no recov.
786 (n)
428 (n)
Tau2 = 0.24, I2 = 81.3%, p = 0.21
Prophylaxis
38%
0.62 [0.30-1.31]
690/2,339
702/1,669
38% improvement
All studies
38%
0.62 [0.30-1.31]
690/2,339
702/1,669
38% improvement
2 metformin COVID-19 recovery results
c19early.com/mf May 2022
Tau2 = 0.24, I2 = 81.3%, p = 0.21
Favors metformin
Favors control
Figure 10. Random effects meta-analysis for recovery.
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Huh
4%
0.96 [0.82-1.12]
cases
population-based cohort
Improvement, RR [CI]
Treatment
Control
Oh (PSM)
28%
0.72 [0.63-0.81]
cases
390/5,946
541/5,946
Holt
-27%
1.27 [0.72-2.22]
cases
12/429
434/14,798
Blanc
-44%
1.44 [1.00-2.07]
cases
11/16
78/163
MacFadden
1%
0.99 [0.96-1.01]
cases
n/a
n/a
Tau2 = 0.02, I2 = 86.3%, p = 0.6
Prophylaxis
4%
0.96 [0.82-1.12]
413/6,391
1,053/20,907
4% improvement
All studies
4%
0.96 [0.82-1.12]
413/6,391
1,053/20,907
4% improvement
5 metformin COVID-19 case results
c19early.com/mf May 2022
Tau2 = 0.02, I2 = 86.3%, p = 0.6
Favors metformin
Favors control
Figure 11. Random effects meta-analysis for cases.
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Reis (DB RCT)
1%
0.99 [0.88-1.11]
viral+
215 (n)
203 (n)
Improvement, RR [CI]
Treatment
Control
Tau2 = 0.00, I2 = 0.0%, p = 0.85
Early treatment
1%
0.99 [0.88-1.11]
0/215
0/203
1% improvement
All studies
1%
0.99 [0.90-1.09]
0/215
0/203
1% improvement
1 metformin COVID-19 viral clearance result
c19early.com/mf May 2022
Tau2 = 0.00, I2 = 0.0%, p = 0.85
Favors metformin
Favors control
Figure 12. Random effects meta-analysis for viral clearance.
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Reis (DB RCT)
27%
0.73 [0.28-1.94]
death
7/215
9/203
Improvement, RR [CI]
Treatment
Control
Tau2 = 0.00, I2 = 0.0%, p = 0.54
Early treatment
27%
0.73 [0.28-1.94]
7/215
9/203
27% improvement
Tamura
97%
0.03 [0.00-0.58]
death
115 (n)
73 (n)
Improvement, RR [CI]
Treatment
Control
Tau2 = 0.00, I2 = 0.0%, p = 0.019
Late treatment
97%
0.03 [0.00-0.58]
0/115
0/73
97% improvement
Luo
75%
0.25 [0.07-0.84]
death
3/104
22/179
Improvement, RR [CI]
Treatment
Control
Wang
58%
0.42 [0.01-1.98]
death
1/9
13/49
Chen
33%
0.67 [0.20-1.78]
death
4/43
15/77
Kim
64%
0.36 [0.10-1.23]
death
113 (n)
122 (n)
Li
78%
0.22 [0.09-0.54]
death
2/37
21/94
Goodall
3%
0.97 [0.75-1.25]
death
74/210
280/771
Gao
-225%
3.25 [1.03-7.41]