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.
Medscape Medical News invited three experts to weigh in.
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.
Interestingly, these agents also suppress the reward, intake, and motivation to consume other addictive drugs like cocaine, amphetamine, nicotine, and some opioids, Jerlhag Holm, professor, Department of Pharmacology, University of Gothenburg, Sweden, noted in an email.
In a recently published preclinical study, her group provides evidence to help explain anecdotal reports from patients with obesity treated with semaglutide who claim 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,” said Jerlhag Holm.
“AUD is a heterogenous disorder, and one medication is most likely not helpful for all AUD patients,” she added. “Therefore, an arsenal of different medications is beneficial when treating AUD.”
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 [GLP-1 agonists] impacts cravings and could impact addictive behaviors.”
“I would say, overall, the jury is still out,” as to whether anecdotal reports of GLP-1 agonists curbing addictions will be borne out in randomized controlled trials.
“I think it is much too early to tell” whether these drugs might be approved for treating addictions without more solid clinical trial data, noted Hwang, who is an associate professor of medicine and chief, Division of Endocrinology and Metabolism, at the University of North Carolina, 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 participants with AUD who are also smokers.
They aim to determine if patients who receive semaglutide at escalating doses (0.25 mg to 1.0 mg per week via subcutaneous injection) over 9 weeks will consume less alcohol (the primary outcome) and smoke less (a secondary outcome) than those who receive a sham placebo injection. Results are expected in October 2023.
Fink-Jensen has received an unrestricted research grant from Novo Nordisk to investigate the effects of GLP-1 receptor stimulation on weight gain and metabolic disturbances in patients with schizophrenia treated with an antipsychotic.
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