Could semaglutide reduce the likelihood of nicotine use?

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GLP1 receptor agonists have health benefits that continue to evolve, from blood sugar improvement, to weight loss, reduction in cardiovascular risk, benefits to the heart, liver, and other obesity-related health conditions. Some GLP1 receptor agonists may have a benefit not only to reduce appetite, but also the reward of food, and possibly even alcohol. Semaglutide (Ozempic/Wegovy) has an effect on the reward system of eating, with reduction in cravings and reduced desire for some types of highly palatable food.

So, the question was asked: could semaglutide (Ozempic) use reduce the likelihood of nicotine use?

This question was examined with two recent studies.

The first study was a retrospective cohort study using the TriNetX database of over 100 million people in USA. They looked at people with type 2 diabetes prescribed semaglutide, and propensity score-matched with people receiving other diabetes medications – specifically sitagliptin (Januvia), empagliflozin (Jardiance), and glipizide (Glucotrol, a sulfonylurea).

The study found that people prescribed semaglutide had a lower risk of nicotine use compared to people prescribed empagliflozin (matched cohort of 22,584, 23% lower risk) or glipizide (matched cohort 19,206, 28% lower risk), but not sitagliptin (matched cohort of 23,386 people, 18% lower risk – not statistically significant after adjustment for multiple comparisons). The reduction in likelihood of nicotine use was similar when they looked at new smokers, or people who stopped smoking.

A second study also used TriNetX data to compare evidence of tobacco use (medical encouters for tobacco use, prescription of smoking cessation medication, or smoking cessation counseling) amongst people with type 2 diabetes prescribed semaglutide vs 7 other diabetes medications as their first diabetes treatment. Within a 1-year follow up, they found that semaglutide was associated with a lower risk for medical encounters for tobacco use compared with all other diabetes medications, including other GLP1 receptor agonists (note: tirzepatide (Mounjaro) was not included in the analysis). The differences occurred within 30 days of starting medication in most cases.

There are many possible reasons that could explain these results. Could semaglutide make a person less likely to use nicotine by affecting the reward pathway of nicotine in the brain? This is a possibility worth exploring with further research.

It is also possible that a person engaging in a new health journey with semaglutide, which improves not only sugars but also weight, may find new motivation to stop smoking alongside this health journey, or be less likely to start smoking while on a new positive health journey.

Many people who smoke fear the weight gain that often ensues with stopping smoking, so perhaps starting semaglutide gives people the confidence to stop smoking with the reduction in appetite that they may be enjoying with semaglutide.

It is also entirely possible that these findings may not actually represent a true reduction in nicotine use, inherent to limitations of database analyses. There may be something different about people prescribed semaglutide vs other diabetes medications that was not accounted for in the analyses. In the second study, it is possible that there simply wasn’t time to discuss tobacco use in people using semaglutide because other issues were being discussed at medical visits – especially given that most differences were seen in the first 30 days, when there may be the most need for discussion focused on semaglutide (understanding dose titration, managing potential GI side effects, etc).

We also want to keep in mind that naltrexone/bupropion (Contrave) is a weight management medication that contains a smoking cessation agent (bupropion, aka Zyban), though the dosing is different. Although Contrave hasn’t specifically been assessed for smoking cessation in clinical trials, a small, 24-week open label trial of nicotine-dependent people with elevated weight suggested that Contrave use was associated with decreased nicotine use without significant weight gain.

BOTTOM LINE: These studies suggest that people taking semaglutide may be less likely to use nicotine, but these database analyses are far from conclusive. These are fascinating and hypothesis-generating findings that need to be studied more rigorously in randomized, controlled, prospective clinical trials.

Thanks to neuroscientist Cayla Denney who first tuned me into this topic some time ago!

Disclaimer: I receive honoraria as a continuing medical education speaker and consultant from the maker of semaglutide (Novo Nordisk) and naltrexone/bupropion (Bausch). I am/have been an investigator in clinical trials of semaglutide.

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