Mitochondria and the Repurposing of Diabetes Drugs for Off-Label Health Benefits

Abstract

This review describes our current understanding of the role of the mitochondria in the repurposing of the anti-diabetes drugs metformin, gliclazide, GLP-1 receptor agonists, and SGLT2 inhibitors for additional clinical benefits regarding unhealthy aging, long COVID, mental neurogenerative disorders, and obesity. Metformin, the most prominent of these diabetes drugs, has been called the "Drug of Miracles and Wonders," as clinical trials have found it to be beneficial for human patients suffering from these maladies. To promote viral replication in all infected human cells, SARS-CoV-2 stimulates the infected liver cells to produce glucose and to export it into the blood stream, which can cause diabetes in long COVID patients, and metformin, which reduces the levels of glucose in the blood, was shown to cut the incidence rate of long COVID in half for all patients recovering from SARS-CoV-2. Metformin leads to the phosphorylation of the AMP-activated protein kinase AMPK, which accelerates the import of glucose into cells via the glucose transporter GLUT4 and switches the cells to the starvation mode, counteracting the virus. Diabetes drugs also stimulate the unfolded protein response and thus mitophagy, which is beneficial for healthy aging and mental health. Diabetes drugs were also found to mimic exercise and help to reduce body weight.

Keywords: GLP-1 receptor agonists; SGLT2 inhibitors; gliclazide; long COVID; mental neurogenerative disorders; metformin; obesity; unhealthy aging.

Figure 1

Diabetic medications and the mitochondria.

Figure 2

Mode of action of existing drugs that have potential to reverse viral-induced metabolic changes in the mitochondria and hence are candidates targeting treatment of mitochondrial dysfunction in long COVID.

Figure 3

How anti-diabetic drugs improve mental health by modulating mitochondrial dynamics and function.

Figure 4

Diagram summarizing how metformin, gliclazide, GLP-1 receptor agonists, and SGLT-2 inhibitors could be used in combination to produce synergistic effects, resulting in more consistent weight loss outcomes.