June 13, 2023 – Could the class of new weight loss drugs including semaglutide – approved as Ozempic to treat type 2 diabetes and Wegovy to treat obesity – also curb addictions and compulsive behaviors?
As demand for semaglutide for weight loss grew after Wegovy was approved by the FDA in June 2021, personal accounts of unexpected added benefits also began to surface for the class of medications known as GLP-1s, which mimic a natural hormone called glucagon-like peptide-1 that helps a person feel full.
Some patients taking these drugs for type 2 diabetes or weight loss also lost interest in addictive and compulsive behaviors such as drinking alcohol, smoking, shopping, nail biting, and skin picking, as reported in articles in The New York Timesand The Atlantic, among others. For now, the reports are merely anecdotal, so they’re subjective and not yet clinically verified. But there’s also some early research to support these observations.
Recent and Upcoming Studies
“I hope that GLP-1 analogs in the future can be used against [alcohol use disorder], but before that can happen, several GLP-1 trials [are needed to] prove an effect on alcohol intake,” said Anders Fink-Jensen, MD, the senior author of a recent randomized controlled trial of 127 patients with alcohol use disorder, or AUD.
His study involved patients receiving 26 weeks of the first-generation GLP-1 agonist exenatide approved for type 2 diabetes, but this did not reduce the number of heavy drinking days, compared to a placebo.
But in analyses done after the study ended, heavy drinking days and total alcohol intake were significantly reduced in the subgroup of patients with AUD and obesity as determined by a body mass index, or BMI, over 30.
The participants were also shown pictures of alcohol or neutral subjects while they had functional magnetic resonance imaging (MRI). Those who had received exenatide vs. a placebo had significantly less activation in their brains’ reward centers when shown the pictures of alcohol.
This shows that “something is happening in the brain and activation of the reward center is hampered by the GLP-1 compound,” said Fink-Jensen, a clinical psychologist at the Psychiatric Centre Copenhagen in Denmark.
“If patients with AUD already fulfill the criteria for semaglutide (or other GLP-1 analogs) by having type 2 diabetes and/or a BMI over 30, they can of course use the compound right now,” he said.
His team is also beginning a study, in patients with AUD and a BMI of 30 or above, to investigate the effects of semaglutide up to 2.4 milligrams weekly on alcohol intake. This is the maximum dose of semaglutide approved for obesity in the U.S.
“Based on the potency of exenatide and semaglutide,” Fink-Jensen said, “we expect that semaglutide will cause a stronger reduction in alcohol intake” than exenatide.
Animal studies have also shown that GLP-1 agonists suppress alcohol-induced reward, alcohol intake, motivation to consume alcohol, alcohol seeking, and relapse drinking of alcohol, according to researcher Elisabet Jerlhag Holm, PhD.
These agents also suppress the reward, intake, and motivation to consume other addictive drugs like cocaine, amphetamine, nicotine, and some opioids, said Jerlhag Holm, a professor in the Department of Pharmacology at the University of Gothenburg in Sweden.
Her group recently published results of a study done in rats that provides evidence to help explain the anecdotal reports from patients with obesity treated with semaglutide who claimed they also reduced their alcohol intake. In the study, semaglutide both reduced alcohol intake (and relapse-like drinking) and decreased body weight of rats of both sexes.
“Future research should explore the possibility of semaglutide decreasing alcohol intake in patients with AUD, particularly those who are overweight,” Jerlhag Holm said.
“AUD is a … disorder [involving various components], and one medication is most likely not helpful for all AUD patients,” she said, “and therefore an arsenal of different medications is beneficial when treating AUD patients.”
Janice J. Hwang, MD, MHS, echoed these thoughts.
“Anecdotally, there are a lot of reports from patients (and in the news) that this class of medication impacts cravings and could impact addictive behaviors,” she said.
Still, “I think it is much too early to tell” whether these drugs might be approved for treating patients for addictions without more solid clinical trial data, said Hwang, an associate professor of medicine and chief of the Division of Endocrinology and Metabolism at the University of North Carolina at Chapel Hill.
Meanwhile, another research group at the University of North Carolina at Chapel Hill, led by psychiatrist Christian Hendershot, PhD, is conducting a clinical trial in 48 people with AUD who are also smokers.
They aim to determine if patients who receive semaglutide shots at increasingly higher doses over 9 weeks will drink less alcohol and smoke less than those who receive a placebo shot. Results are expected in October.
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