Weight-loss drug shows potential in smoking cessation

Health and Wellness 27. jun 2023 3 min Associate Professor Christoffer Clemmensen Written by Kristian Sjøgren

Weight-loss drugs based on glucagon-like peptide-1 (GLP-1) appear to reduce the urge to smoke tobacco. Conversely, new research in mice shows that administering nicotine and a weight-loss drug as a combination produces greater weight loss than their separate effects. A researcher says that the effect of nicotine and weight-loss drugs needs to be investigated by examining the results of major clinical trials that have already been carried out with weight-loss drugs.

All over the world, people have been using weight-loss drugs on an unprecedented scale. Some users are non-smokers, but some are addicted to tobacco products, including not only cigarettes but also snuff and other nicotine-containing products.

New research in mice shows that administering a combination weight-loss drug based on an GLP-1 receptor agonist and nicotine has unexpected effects.

GLP-1 receptor agonists may indeed reduce the urge to smoke and thus may promote smoking cessation. In addition, administering a combination weight-loss drug and nicotine produces greater weight loss than that achieved by using a weight-loss drug or nicotine alone or the two together but separately.

“This is a provocative conclusion that people who smoke or use another nicotine-containing product may derive greater benefit by being treated with a weight-loss product. Conversely, our study also indicates that using a weight-loss drug based on a GLP-1 receptor agonist reduces the craving for nicotine. GLP-1 receptor agonists thus have an interesting interaction with nicotine, which can perhaps be used to both lose more weight and promote smoking cessation,” explains a researcher involved in the study, Christoffer Clemmensen, Associate Professor, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen.

The research has been published in Cell Reports.

GLP-1 receptor agonists reduce nicotine craving

Not surprisingly, both weight-loss drugs and nicotine-containing products are associated with weight loss, something that many smokers who quit discover when they put on a few extra kilos.

The combination of nicotine and weight-loss drugs appears to interact directly in the brain. Researchers became aware of this in 2017, when a study showed that mice treated with a GLP-1 receptor agonist increased their sensitivity to nicotine, being satisfied with lower doses of nicotine and experiencing discomfort with a high intake.

“The interaction between nicotine and GLP-1 receptor agonists was already noticed then, and in our studies we built on these findings with the aim of investigating the interaction in relation to metabolism and weight loss,” says Christoffer Clemmensen.

Gave mice nicotine and liraglutide

The researchers investigated the effect of combined treatment with both nicotine and the GLP-1 receptor agonist liraglutide on the weight and brains of mice.

The researchers scanned various areas of the brain in real time and detected how administering nicotine changed the release of dopamine. Dopamine is a primary molecular explanation for why people and mice become addicted to tobacco products: an almost unstoppable urge to reward the brain with continual dopamine release.

The researchers also examined the effect of treatment with liraglutide and nicotine in amounts that correspond to those consumed by smokers or people taking a weight-loss drug.

Smoking cessation and increased weight loss

The results show that nicotine and GLP-1 receptor agonists interact to affect both the brain and weight in surprising ways.

The researchers found that obese mice lost more weight through combination treatment with liraglutide and nicotine than what would be expected from the two treatments separately.

According to Christoffer Clemmensen, this suggests that nicotine does not just augment weight loss by amplifying the effect of weight-loss drugs but that the combination has a synergistic effect driven by reduced appetite, a changed reward system and increased energy expenditure.

The results also confirmed that administering nicotine and liraglutide in combination affect the areas of the brain related to appetite regulation and reward, with the reward system producing interesting findings.

Administering only nicotine to the mice increased the levels of dopamine in the brain. However, giving both liraglutide and nicotine attenuated the effect of nicotine on the reward system, since liraglutide reduced the release of dopamine caused by nicotine intake.

“This suggests that GLP-1 receptor agonists can affect the brain in a way that reduces the likelihood of becoming addicted. This may have wider implications than just nicotine, perhaps also attenuating the craving for other addictive substances, including alcohol, which utilises the same reward system in the brain,” explains Christoffer Clemmensen.

Studies involving people required

According to Christoffer Clemmensen, the two interesting conclusions are that nicotine appears to boost the effect of GLP-1 receptor agonists as weight-loss agents and that GLP-1 receptor agonists appear to reduce cravings for nicotine.

He would like to see both aspects investigated in studies involving people, but before initiating new larger studies in which people are randomised to nicotine and weight-loss drugs, data clues might already be available.

Christoffer Clemmensen says that the studies that have already been done with weight-loss drugs can provide an idea of the association. The data will show whether participants in GLP-1-based weight-loss trials used tobacco, and post-hoc analysis may therefore determine whether smokers lost more weight than non-smokers by using a GLP-1 receptor agonist or whether more smokers taking a GLP-1 receptor agonist stopped smoking than people not taking it.

Christoffer Clemmensen adds that he would very much like to contribute to studies mapping how the combination of GLP-1 receptor agonists and nicotine affects people.

“It will be exciting to explore if we can replicate the results found with mice. In addition, this may indicate how drug therapy could achieve greater weight loss or whether GLP-1 receptor agonists should perhaps be used in smoking cessation,” concludes Christoffer Clemmensen.

GLP-1 and nicotine combination therapy engages hypothalamic and mesolimbic pathways to reverse obesity” has been published in Cell Reports. The Lundbeck Foundation and Novo Nordisk Foundation funded the research. Several co-authors of the article are affiliated with the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen.

The Clemmensen Group studies the biological regulation of body weight and aims at transforming molecular and physiological insights into innovative th...

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