Metformin reduces mortality in diabetic patients with COVID-19

Treatment with metformin appears to lower the risk of mortality for COVID-19 patients with diabetes, according to a meta-analysis presented at the virtual conference of the Endocrine Society (ENDO 2021). However, only one study examined the in-hospital use of metformin.

Chenyu Sun from the AMITA Health Saint Joseph Hospital Chicago, Chicago, IL, US, led the team of researchers. They conducted a comprehensive literature search on PubMed and Web of Science to identify all relevant studies published prior to October 2020 according to the established inclusion criteria. The meta-analysis was reported in accordance with the Preferred Reporting Project declared by the Systematic Review and Meta-Analysis (PRISMA).

The Newcastle-Ottawa Scale (NOS) was used to perform the quality assessment. To examine the association between metformin use and mortality for COVID-19 patients, pooled odds ratio (OR) and 95 percent confidence intervals (CIs) were calculated. A random-effect or fixed-effect model was used based on heterogeneity significance.

Then, the researchers carried out a subgroup analysis based on in-hospital use or home use, and different sample sizes, as well as sensitivity analysis and publication bias. RevMan software (version 5.3; Cochrane Library) and STATA 12.0 statistical software were used to perform all statistical analyses. In addition, all p values were two-tailed, and the test level was 0.05.

Overall, 97 articles were identified from the database search and five from other sources. Only eight articles including a total of 11,169 participants were eligible for meta-analysis, most of which were of moderate quality. [ENDO 2021, abstract P22-8]

Use of metformin showed a statistically significant association with reduced mortality among patients with COVID-19 (OR, 0.53, 95 percent CI, 0.34–0.83; p=0.005; I², 77 percent). Subgroup analyses also revealed that home-use of metformin correlated with a lower mortality risk (OR, 0.54, 95 percent CI, 0.35–0.84; p=0.006; I², 66 percent). However, one study on in-hospital use did not find any survival benefits of using metformin (OR, 1.65, 95 percent CI, 0.71–3.86; p=0.247).

No statistically significant reduced risk of mortality (OR, 0.84, 95 percent CI, 0.57–1.26; p=0.41; I², 73 percent) was observed for sample size >1,000, but for those ≤1,000, the risk of mortality substantially decreased (OR, 0.29, 95 percent CI, 0.19–0.44; p<0.00001; I², 0 percent).

The relative stability of the result was confirmed in sensitivity analysis by changing fixed-effect models to random-effect models and by omitting each study at a time. No significant risk of publication bias was detected in Begg’s test (z, 0.37; p=0.711) and Egger’s test (t, –1.98; p=0.096).

One of the earliest studies on metformin use in diabetic patients with COVID-19 also found a decreased mortality in those who received treatment as opposed to diabetics not receiving metformin. However, in-hospital mortality was significantly lower in the metformin group (2.9 percent vs 12.3 percent; p=0.01). [Am J Trop Med Hyg 2020;103:69-72]

“More high-quality original studies are needed to further explore the association between metformin use and mortality risk of COVID-19,” the researchers said.