MINNEAPOLIS -- Could GLP-1 medications curb problem drinking in the same way that they cut eating in people who are overweight or obese?

The Minneapolis VA Health Care System and 18 other federal hospitals are recruiting more than 600 veterans with alcohol use disorder to answer the question and try to add another needed medication to the menu of substance-abuse treatments.

“There hasn’t been a new medication treatment [for alcohol abuse] that’s been approved in over two decades,” said Dr. Eric Dieperink, a Minneapolis VA staff psychiatrist leading the local arm of the study.

GLP-1s such as semaglutide have proven effective albeit expensive solutions for obesity, contributing to the first decline in Minnesota’s obesity rate since the late 1990s. The daily injectable and oral drugs work by mimicking a hormone in the gut that signals fullness and slows digestion.

How they might impact alcohol usage is unclear. The sense of fullness that curbs eating might also curb drinking, or perhaps the drug’s side effects such as nausea have an impact, said Joseph Schacht, a University of Colorado researcher. He just completed a smaller trial showing that heavy drinkers cut alcohol consumption when taking GLP-1 medications.

“A more intriguing possibility is that semaglutide affects ... parts of the brain associated with reward, and that this effect makes people less likely to pursue rewarding substances like alcohol,” he said.

Whatever their mechanism, GLP-1s could kickstart renewed interest in medications to treat alcohol use disorder. Other options exist, including naltrexone, which is commonly used to treat opioid-use disorder. But only about 3% of people with alcohol use disorder try medication-assisted treatment, according to recent federal surveys.

Treatment in the U.S. historically has been dominated by the group therapy approach, offered by Alcoholics Anonymous and others, that urges abstinence. Medications in some groups have been dismissed because they’re seen as a crutch rather than recovery, or they help reduce but not eliminate alcohol consumption.

The popularity of GLP-1s for weight loss, and the familiarity of brand names such as Wegovy and Ozempic, could make them appealing, Dieperink said. The Minneapolis researcher has published multiple studies on the effectiveness of medications and why primary care doctors have hesitated to prescribe them.

“Acceptance seems pretty high,” he said of GLP-1s. “My guess is that people probably know someone who has tried it or who is on one of these medications.”

Declining cost and improving insurance coverage could help. Manufacturer discounts have made GLP-1s more affordable for patients at Hazelden Betty Ford Foundation, said Dr. Alta DeRoo, chief medical officer of the addiction medicine provider based in Center City, Minnesota.

Prescribing GLP-1s to curb drinking is considered off-label, which often prevents insurance coverage, DeRoo said. But many of Hazelden’s patients also qualify for the drug’s on-label benefits because they struggle with their weight, she said, “primarily because of the amount of sugar and calories with alcohol.”

The first inklings that GLP-1s curbed drinking emerged on social media, DeRoo said, suggesting that people will embrace the drugs.

The stigma that its a character flaw to take medications for alcohol abuse is fading, she added. “That’s a more archaic way of thinking, that you have to white knuckle it and not use any of these medications.”

It is fitting that the VA would solve this question, Dieperink said. VA researchers in New York discovered the hormone in Gila monster venom that inspired the first GLP-1 medication to manage diabetes. Alcohol use disorder also is more common among veterans than the rest of the U.S. population.

Enrollees in the clinical trial will either receive daily injections over six months of semaglutide or a non-medicating placebo of saline for comparison. The study is recruiting veterans who consume heavy amounts of alcohol — about four or more drinks per day for men and three or more drinks per day for women.

Success will be measured by whether veterans on the medication reduce their drinking levels more than the placebo group, and whether they avoid days of heavy drinking. The U.S. Food and Drug Administration last year endorsed a reduction in drinking as an appropriate goal for studies of treatments for alcohol use disorder, rather than only abstinence.

Researchers in Pennsylvania are leading the VA study, known by the acronym CRAVE (Cessation or Reduction of Alcohol Consumption in Veterans). It is considered a Phase 3 study, often the final step before the FDA approves a new drug or expand an old drug’s usage.

Smaller studies offer reasons for optimism. Schacht’s study in Colorado suggested GLP-1 usage to curb drinking was safe, and was one of the first to show heavy drinkers cut alcohol consumption while on the medication.

The 50 participants didn’t lose weight during the eight-week study, nor did they reduce the days on which they drank any alcohol, the study showed. But days of heavy drinking declined, which made sense to Schacht.

“In people who take it for weight reduction, it doesn’t cause them to stop eating, just to eat less,” he said. “I think that GLP-1 receptor agonists may fundamentally be ‘moderation molecules.’”

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