. 2020 Jun 10;165:108268. doi: 10.1016/j.diabres.2020.108268

Table 1.

Effect of metformin on lung diseases and mortality in experimental studies and patients with diabetes with or without COVID-19.

Metformin	Outcomes
Studies in patients with diabetes and COPD or sepsis [18], [19], [20], [21]	• Meta-analysis of 5 observational studies found metformin users had a significantly less mortality compared to the non-users, during the sepsis (OR 0.59; 95% CI, 0.43–0.79, p = 0.001). • Meta-analysis of 17 observational studies found metformin users had a significantly lesser incidence of active tuberculosis (RR 0.51; 95% CI, 0.38–0.69, p < 0.001) and mortality, compared to the non-users (RR 0.34; 95% CI, 0.20–0.57, p < 0.001). • After the adjustment for multiple confounding factors, metformin users had a significantly decreased risk of mortality in patients with COPD compared to the non-users, in a median 6.2 years of follow up (HR 0.30; 95% CI, 0.10–0.93). • Patients with COPD had a significantly lower risk of death in metformin users compared to the non-users, in a 2-year follow up study (HR 0.46; 95% CI, 0.23–0.92).
Studies in patients with diabetes and COVID-19 [22], [23], [24], [25]	• Well-controlled cohorts with diabetes (receiving metformin in 39%) had a significant reduction in all-cause mortality, compared to the poorly-controlled cohorts (receiving metformin in 26%) after a 1:1 propensity matching (adjusted HR 0.13; 95% CI, 0.04–0.44, p < 0.001). • Metformin users had a significantly higher albumin level (38.6 vs. 36.7 g/L, p = 0.04) and lower IL-6 level (4.1 vs. 11.1 pg/mL, p = 0.02) compared to the non-users. A trend of decreased in-hospital deaths was observed in metformin users, compared to the non-users (9.3 vs. 19.5%, p = 0.19). • In an unadjusted analysis, metformin users had a lower rate of death, compared to the non-users (OR 0.59; 95% CI, 0.42–0.84, p = nr). A trend of lower rate of death was also observed in metformin users compared to non-users, even after the full adjustment (OR 0.80; 95% CI, 0.45–1.43; p = 0.45). • Metformin users had a significantly less in-hospital mortality compared to the non-users (2.9 vs. 12.3%, p = 0.01). Four-fold decrease in-hospital death in metformin users compared to the non-users, in a multi-variate analysis (OR 4.36; 95% CI, 1.22–15.59, p = 0.02).

Metformin

Outcomes

Studies in patients with diabetes and COPD or sepsis [18], [19], [20], [21]

•
Meta-analysis of 5 observational studies found metformin users had a significantly less mortality compared to the non-users, during the sepsis (OR 0.59; 95% CI, 0.43–0.79, p = 0.001).
•
Meta-analysis of 17 observational studies found metformin users had a significantly lesser incidence of active tuberculosis (RR 0.51; 95% CI, 0.38–0.69, p < 0.001) and mortality, compared to the non-users (RR 0.34; 95% CI, 0.20–0.57, p < 0.001).
•
After the adjustment for multiple confounding factors, metformin users had a significantly decreased risk of mortality in patients with COPD compared to the non-users, in a median 6.2 years of follow up (HR 0.30; 95% CI, 0.10–0.93).
•
Patients with COPD had a significantly lower risk of death in metformin users compared to the non-users, in a 2-year follow up study (HR 0.46; 95% CI, 0.23–0.92).

Studies in patients with diabetes and COVID-19 [22], [23], [24], [25]

•
Well-controlled cohorts with diabetes (receiving metformin in 39%) had a significant reduction in all-cause mortality, compared to the poorly-controlled cohorts (receiving metformin in 26%) after a 1:1 propensity matching (adjusted HR 0.13; 95% CI, 0.04–0.44, p < 0.001).
•
Metformin users had a significantly higher albumin level (38.6 vs. 36.7 g/L, p = 0.04) and lower IL-6 level (4.1 vs. 11.1 pg/mL, p = 0.02) compared to the non-users. A trend of decreased in-hospital deaths was observed in metformin users, compared to the non-users (9.3 vs. 19.5%, p = 0.19).
•
In an unadjusted analysis, metformin users had a lower rate of death, compared to the non-users (OR 0.59; 95% CI, 0.42–0.84, p = nr). A trend of lower rate of death was also observed in metformin users compared to non-users, even after the full adjustment (OR 0.80; 95% CI, 0.45–1.43; p = 0.45).
•
Metformin users had a significantly less in-hospital mortality compared to the non-users (2.9 vs. 12.3%, p = 0.01). Four-fold decrease in-hospital death in metformin users compared to the non-users, in a multi-variate analysis (OR 4.36; 95% CI, 1.22–15.59, p = 0.02).

OR: odds ratio, RR; risk ratio, HR: hazard ratio, COPD: chronic obstructive pulmonary diseases, IL-6: interlukin-6, nr: not reported, COVID-19: coronavirus disease-19.