Researchers say that the promising COVID-19 medications hydroxychloroquine and chloroquine may be toxic when combined with the diabetes medication metformin.
The researchers’ study found that 30 to 40 percent of mice given a combination of metformin and either hydroxychloroquine or chloroquine died. No effect on survival rate occurred when mice were given the same dose of either medication alone.
The study was undertaken before the current coronavirus outbreak and the results are unexpectedly timely and serendipitous. The researchers said they decided to study the two drugs together because both drugs have demonstrated efficacy against pancreatic cancer. Some of the mice in the study had pancreatic cancer. However, the drug combination was similarly fatal for mice without pancreatic cancer.
The researchers said the drug combination may be toxic because hydrochloroquine, chloroquine and metformin all affect a process known as autophagy. Autophagy is the process by which cells recycle aging proteins which lets them synthesize new proteins. Hydrochloroquine and chloroquine are autophagy inhibitors whereas metformin can induce autophagy.
Some drugs behave differently in humans than they do in mice, so the results of this study do not necessarily mean the drug combination will be toxic in humans. The study has also not been peer-reviewed.
Hydroxychloroquine and chloroquine are malaria medications which have shown promise in treating COVID-19, the disease caused by the novel coronavirus SARS-CoV-2. A French study found a 100% success rate in treating COVID-19 with a combination of hydroxychloroquine and azithromycin and a follow-up study found that COVID-19 patients treated with the drug combination had significantly lower levels of the SARS-CoV-2 virus in their bodies than the then-existing literature suggested the average COVID-19 patients would have. French researchers say that they’ve treated 2,179 COVID-19 patients with the drug combination as of today and only nine of them have died, representing a mortality rate of 0.4%. Johns Hopkins University statistics say that as of today there have been 1,414,738 confirmed cases of COVID-19 worldwide and 81,259 deaths, representing a mortality rate of 5.7%.
Metformin has recently been in the news because the probable carcinogen N-nitrosodimethylamine (NDMA) has been detected in the medication. The Health Sciences Authority of Singapore discovered NDMA in three medications containing metformin and testing lab Valisure found NDMA in 16 of 38 batches of the drug. This prompted Valisure to petition the U.S. Food and Drug Administration to recall the tainted batches of metformin.