Could Semaglutide Treat Addiction as Well as Obesity?
Could glucagon-like peptide-1 (GLP-1) receptor agonists such as semaglutide — approved as Ozempic to treat type 2 diabetes and as Wegovy to treat obesity, both from Novo Nordisk — also curb addictions and compulsive behaviors?
As demand for semaglutide for weight loss grew following approval of Wegovy by the US Food and Drug Administration in 2021, anecdotal reports of unexpected potential added benefits also began to surface.
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 Times and The Atlantic among others.
There is also some preliminary research to support these observations.
Recent and Upcoming Studies
The senior author of a recent randomized controlled trial of 127 patients with alcohol use disorder (AUD), Anders Fink-Jensen, MD, told Medscape Medical News: "I hope that GLP-1 analogs in the future can be used against AUD, but before that can happen, several GLP-1 trials [are needed to] prove an effect on alcohol intake."
His study involved patients who received exenatide (Byetta, Bydureon, AstraZeneca) over 26 weeks, the first-generation GLP-1 agonist approved for type 2 diabetes, but treatment did not reduce the number of heavy drinking days (the primary outcome) compared with placebo.
However, in post-hoc, exploratory analyses, heavy drinking days and total alcohol intake were significantly reduced in the subgroup of patients with AUD and obesity (body mass index [BMI] > 30 kg/m2).
The participants were also shown pictures of alcohol or neutral subjects while they underwent functional magnetic resonance imaging. Compared with placebo, those who had received exenatide had significantly less activation of brain reward centers when shown the pictures of alcohol.
"Something is happening in the brain and activation of the reward center is hampered by the GLP-1 compound," Fink-Jensen, a clinical psychologist at the Psychiatric Centre Copenhagen, Denmark, remarked in an email.
"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 kg/m2, they can of course use the compound right now," he noted.
His team is also beginning a study in patients with AUD and a BMI ≥ 30 kg/m2 to investigate the effects on alcohol intake of semaglutide up to 2.4 mg weekly, the maximum dose currently approved for obesity in the United States.
"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, Elisabet Jerlhag Holm, PhD, noted.
