Loading ...

LOS ANGELES — Treating nicotine addiction with glucagon-like peptide 1 receptor agonists (GLP-1 RAs) was associated with less weight gain compared with other smoking cessation treatments such as nicotine patches and varenicline, results of a new review suggested.

“GLP-1 RAs may serve as a safe adjunctive therapy for smoking cessation, especially in patients who are more prone to relapsing due to weight gain, such as women and obese patients,” study author Débora Xavier, MD, Universidade Federal do Pará and Fundação Oswaldo Cruz in Brazil, told Medscape Medical News.

The findings, presented on May 17 at the American Psychiatric Association (APA) 2025 Annual Meeting, add to the growing body of evidence supporting the use of GLP-1 RAs to manage various types of addiction.

Weight Gain Common

Cigarette smoking is the leading cause of preventable disease, disability, and death in the United States. Although smoking cessation aids are widely available, long-term abstinence is still challenging, especially in vulnerable populations, due to intense cravings and post-cessation weight gain, said Xavier.

It’s not unusual for ex-smokers to gain 4 or 5 kg (8-11 lb) after quitting cigarettes, she explained. “That’s one of the most common reasons for relapsing.”

The role of GLP-1 RAs, approved to treat obesity or type 2 diabetes, in smoking cessation is unclear, although the drugs have shown promise in modulating reward pathways in the brain, said Xavier.

Beyond that, “nicotine has anorexigenic effects, reinforcing one more biologically plausible pathway for GLP-1 RAs’ benefits for smoking cessation,” she added.

The review included three randomized controlled trials that enrolled 410 smokers, 207 of whom received a GLP-1 RA. One study was from the United States (published in 2021), one from Denmark (2022), and one from Switzerland (2023). The study periods ranged from 6 to 26 weeks.

The US study compared exenatide (2 mg weekly) with placebo plus nicotine patch and counseling. The Danish study also investigated exenatide 2 mg weekly but compared the drug with a placebo plus cognitive-behavioral therapy. And the Swiss study compared dulaglutide (1.5 mg weekly) with placebo plus varenicline, a nicotinic receptor partial agonist.

The outcomes were post-cessation weight gain and abstinence rates obtained either through self-report or a carbon monoxide breath test.

Less Weight Gain

People taking GLP-1 RAs gained a mean of 2.59 kg (5.7 lb) less than those in the control group (95% CI, −3.70 to −1.48 kg; P < .00001), with moderate heterogeneity (35%).

“We can confidently identify these results as significant,” said Xavier. “We came to the conclusion that patients from the group receiving GLP-1 receptor agonists experienced less weight gain.”

The analysis was less conclusive regarding abstinence, with the odds ratio (OR) only slightly above zero (OR, 1.22; 95% CI, 0.71-2.10). The lack of statistical significance could have been due to the short study periods, Xavier said.

Still, she noted, the fact that participants in the study gained less weight when quitting smoking is important.

“The intervention is highly promising because, when you think about it, patients who stop smoking usually gain weight, and with that comes worrisome cardiovascular outcomes. That didn’t happen here; the patients gained less weight, and some even lost weight,” she said.

The quit rates observed in the studies were broadly comparable to those seen with standard therapy, said Xavier. In one study, for example, people using a GLP-1 RA and the nicotine patch had a 46% quit rate, “which is comparable to nicotine patch alone or even better.”

“So, GLP-1 drugs didn’t clearly make people more likely to quit, but they seem about as effective as standard treatments, especially when used together with something like a nicotine patch,” Xavier said.

Further research is needed to explore the potential benefits of GLP-1 RAs for smoking cessation across different subgroups, including patients with obesity, she said.

As this work is preliminary, clinicians considering off-label prescriptions of GLP-1 RAs for smoking cessation should use them as adjunct therapy and personalize treatment for each patient, said Xavier.

Asked if clinicians should be concerned about recently identified psychiatric side effects or suicidality possibly linked to GLP-1 RAs, Xavier noted these outcomes weren’t reported in the included trials.

And she stressed these drugs are US Food and Drug Administration–approved. “It’s not uncommon that if you use a drug widely, you’re going to see more widespread adverse effects, but overall, these drugs are considered safe.”

‘Good Starting Point’

Commenting for Medscape Medical News, Smita Das, MD, an addiction psychiatrist and clinical associate professor of psychiatry and behavioral sciences, Stanford School of Medicine, Stanford, California, said this review offers a good starting point, but more research is needed to understand the impact of GLP-1 RAs on both weight gain and nicotine cessation.

“I’m hopeful that more studies will be done and that over time, we’ll get enough data to tell us about how useful this can be for reducing that risk of weight gain, and hopefully, at some point, to reduce or to improve outcomes for addictions,” Das said.

The possibility of gaining weight deters many people from trying to quit smoking. “So if there’s a way for them to not have that weight gain, or as much of that weight gain, they would be very interested,” she added.

Currently available smoking cessation aids reduce the risk for weight gain but don’t eliminate that risk entirely, “so having more tools in our tool belt is important,” Das said.

Also commenting for Medscape Medical News, Howard Liu, MD, chair of the University of Nebraska Medical Center Department of Psychiatry, Omaha, Nebraska, who led the media briefing featuring the study, noted the importance of understanding the underlying factors — including smoking — that may contribute to earlier and higher mortality rates among people with a serious mental illness.

“Although we can’t conclude from this study that we should start patients on GLP-1s for smoking cessation, it’s a reminder that we should team up with primary care providers in models like collaborative care to co-manage physical and mental health issues,” Liu said. “From smoking cessation to obesity to diabetes, these illnesses often benefit from a team approach.”

The study received no outside funding. Xavier and Liu had no relevant conflicts of interest.