Treating obese mice with disulfiram — a drug that doctors usually prescribe for alcohol use disorder — led to significant weight loss and improved metabolic health, a new study reports.
Obesity is a major health problem facing societies across the globe. Rates of obesity have almost tripled since 1975, with at least 650 million adults worldwide now living with this condition.
This high prevalence has made obesity a public health priority, as the consequences of this condition include cardiovascular disease, type 2 diabetes, and a higher risk of some cancers.
The current SARS-CoV-2 pandemic has focused attention on the issue again, as data seem to suggest that obesity also puts people at a higher risk of severe symptoms and complications of COVID-19.
The causes of obesity are complex, and achieving a moderate weight can be difficult. Limited treatment options are available outside of lifestyle changes, and for many, these simply do not lead to significant or sustainable weight loss.
Now, scientists from the National Institute on Aging have led research that may have discovered a new treatment for the condition, in the form of an existing drug that doctors have conventionally used to treat chronic alcohol use disorder.
In the journal Cell Metabolism, the researchers describe data suggesting that it might be possible to repurpose disulfiram to treat people with obesity.
Disulfiram, which is available under the brand name Antabuse, is an established drug for the treatment of chronic alcohol use disorder. It is FDA-approved and has been in use for more than 70 years.
The medical community describes it as an aversive therapy because it causes people to feel unpleasant effects similar to those of a hangover — for example, nausea, headaches, and vomiting — almost immediately after they consume any alcohol.
The researchers behind this study note that disulfiram became of interest to them thanks to recent research in rats that described its anti-inflammatory properties and its benefits, in particular, for people with type 2 diabetes.
To find out whether disulfiram could also be beneficial for obesity, the researchers gave the drug to some young mice that had eaten a high fat diet for 12 weeks.
In this model of obesity, the mice also developed signs of prediabetes, including insulin resistance and higher levels of glucose in their blood after fasting.
The researchers divided the obese mice into four groups, each of which ate a different diet for the next 12 weeks: a standard diet, a high fat diet, a high fat diet plus a low dose of disulfiram, or a high fat diet plus a higher dose of disulfiram.
The mice that received disulfiram, either at a low dose of 0.3 milligrams (mg) each day or a high dose of 0.6 mg each day, showed dramatic weight loss, despite continuing to eat a high fat diet.
As the team expected, the mice who stayed on the high fat diet without any treatment continued to gain weight, whereas those that switched back to a normal diet gradually lost weight.
“When we first went down this path, we did not know what to expect, but once we started to see data showing dramatic weight loss and leaner body mass in the mice, we turned to each other and couldn’t quite believe our eyes.”
– Lead author Dr. Michel Bernier, Ph.D.
The researchers certainly had a reason to be excited, as the mice on the high dose of disulfiram lost up to 40% of their body weight in just 4 weeks.
Metabolic outcomes improved, too. Mice receiving either dose of the drug had significant improvements in their blood glucose levels, reaching a level similar to that of the mice who returned to a normal diet.
The treatment also seemed to protect the pancreas and the liver, both of which can sustain damage due to the metabolic changes associated with obesity.
The researchers believe that this effect stems from disulfiram’s anti-inflammatory properties, which may have helped regulate blood glucose levels in the mice and protect against organ damage.
However, the researchers say more work is necessary to understand the mechanisms underlying the drug’s actions. The team is also planning clinical trials to test whether disulfiram could be beneficial in people with severe obesity.
Importantly, they say that the mechanism by which disulfiram improves metabolic outcomes is separate from its effects on alcohol metabolism. This means that it would be possible to treat people with the drug (or a derivative) without causing adverse reactions to alcohol consumption.
As a final note, the findings of this study are based only on research in animals, and the researchers are not recommending that people use disulfiram for weight loss. It is important that people do not use disulfiram for off-label purposes without FDA approval and robust clinical evidence to support its effectiveness and safety.