GLP-1 Microdosing and Quitting Smoking: Nicotine Cravings, Post Quit Weight Gain, and What the Trials Show

Ask a smoker why they have not quit yet and a surprising number will mention their weight before they mention cravings.

The fear is not irrational. Quitters gain an average of 4 to 5 kg in the first year, and in surveys a large share of smokers, women especially, name weight gain as a reason to keep smoking or to relapse. GLP-1 medicines sit right on top of that problem. They act on appetite, and they also act on the same brain reward circuits that nicotine uses.

This article covers why quitting drives weight up, what two randomized trials found when a GLP-1 was added to standard quit aids, what the animal research says about GLP-1 signalling and nicotine reward, what the 2024 semaglutide real world data shows, and what a low dose protocol can and cannot be expected to do.

Why do people gain weight after they quit smoking?

Nicotine was doing two jobs

People gain weight after quitting because nicotine had been holding appetite down and energy expenditure up, and both effects reverse within days of the last cigarette. Nicotine acts on receptors in the hypothalamus that reduce hunger, and it raises resting energy expenditure by roughly 7 to 15 percent through its stimulant effect on the nervous system. On average, smokers weigh about 4 to 5 kg less than non smokers of the same age.

Behaviour adds to the physiology. A cigarette gives the hands and mouth something to do fifteen or twenty times a day, and food fills that gap easily. Taste and smell also recover after quitting, which makes food more rewarding just as appetite rises.

Aubin and colleagues pooled 62 studies in the BMJ in 2012 to measure the result. Untreated quitters gained 1.12 kg in the first month, 2.85 kg by three months, and 4.67 kg by twelve months. The average hides a wide range. About 16 percent of quitters lost weight, and about 13 percent gained more than 10 kg.

How long does increased hunger last after quitting?

Longer than the other withdrawal symptoms

Increased hunger after quitting usually lasts for months, well beyond the two to four weeks that most other nicotine withdrawal symptoms take to settle. John Hughes reviewed the time course of withdrawal in Nicotine and Tobacco Research in 2007. Irritability, restlessness, poor concentration, and low mood typically peak in the first week and fade over the next few. Appetite was the outlier, often staying elevated for ten weeks or more.

That mismatch matters for anyone thinking about a GLP-1 around a quit attempt. The part of withdrawal that GLP-1 medicines are best known for, appetite and food reward, is the part that lingers. It is also the part that drives the slow, steady weight gain that makes some ex smokers start again.

How could a GLP-1 affect nicotine cravings?

The evidence so far is mostly in animals

GLP-1 receptors sit in several brain areas that handle nicotine reward, and activating them in animals reduces both the dopamine response to nicotine and how much nicotine animals choose to take. Egecioglu and colleagues at the University of Gothenburg showed in 2013 that exendin-4, a GLP-1 receptor agonist, blocked nicotine induced dopamine release in the nucleus accumbens of mice and reduced the preference mice developed for places where they had received nicotine.

A 2017 study in Nature Neuroscience by Tuesta and colleagues went further. GLP-1 producing neurons feed a small circuit running from the medial habenula to the interpeduncular nucleus, a pathway that makes high doses of nicotine feel unpleasant. Switching on GLP-1 receptors there cut nicotine self administration in mice. Mice lacking those receptors took more nicotine. In that model, GLP-1 signalling works as a brake on intake.

The same reward pathways turn up in the research on GLP-1 medicines and alcohol, covered in the alcohol cravings article on this site. Animal findings of this kind often shrink or disappear in human trials, so they explain why researchers are interested rather than proving that the effect is real in people.

Do GLP-1 drugs raise quit rates in human trials?

One positive trial, one neutral one

Two randomized trials have tested a GLP-1 medicine as an add on to standard quit aids, and they disagree on quit rates. The first, led by Luba Yammine at UTHealth Houston and published in Nicotine and Tobacco Research in 2021, enrolled 84 adult smokers with prediabetes or overweight. Everyone used a nicotine patch. Half also received extended release exenatide 2 mg once weekly for six weeks.

At the end of six weeks, 46.3 percent of the exenatide group were abstinent by carbon monoxide testing, against 26.8 percent on placebo. The exenatide group also reported less craving and fewer withdrawal symptoms. Among those who quit, the exenatide group gained about 2.5 kg (5.6 lb) less than the placebo group.

The trial was small and short, with no long term follow up, so the abstinence result is a signal rather than an answer.

What did the dulaglutide and varenicline trial find?

No gain in quitting, a clear gain on weight

The larger trial found that dulaglutide did not improve quit rates on top of varenicline but did prevent the usual weight gain. Lüthi and colleagues at the University Hospital Basel randomized 255 smokers to dulaglutide 1.5 mg weekly or placebo for 12 weeks, and published the results in eClinicalMedicine in 2024. Everyone received varenicline and behavioural counselling.

Abstinence was similar in both arms at 12 weeks, around two thirds, and stayed similar at one year. Weight was different. The placebo group gained about 1.4 kg over 12 weeks, as expected after quitting, while the dulaglutide group lost about 1.0 kg. Nausea and other gut side effects were more common with dulaglutide.

One reading of the two trials is that varenicline already works so well on the nicotine side that a GLP-1 has little room to add, while the appetite side is left open. The exenatide trial used a nicotine patch, a weaker quit aid, which may be why a GLP-1 effect on abstinence was easier to see there.

How do GLP-1s compare with approved quit smoking medicines?

Varenicline is still the benchmark

GLP-1 medicines are not approved for smoking cessation, and the approved options have far more evidence behind them. The EAGLES trial, published by Anthenelli and colleagues in the Lancet in 2016, randomized more than 8,000 smokers across 16 countries. In the cohort without psychiatric illness, continuous abstinence in weeks 9 to 12 was 38.0 percent on varenicline, 26.4 percent on the nicotine patch, 26.1 percent on bupropion, and 13.7 percent on placebo.

EAGLES also settled an older worry. Serious neuropsychiatric side effects were no more common with varenicline or bupropion than with placebo. For anyone planning a quit attempt, one of these approved aids plus counselling is the evidence based starting point, and any role for a GLP-1 is as an add on under a prescriber, most plausibly aimed at weight.

What does real world data show for semaglutide and smoking?

Encouraging, but observational

Real world data suggests people on semaglutide have fewer medical encounters for tobacco use than people on other diabetes drugs. Wang and colleagues at Case Western Reserve University analysed electronic health records of adults with type 2 diabetes and a tobacco use disorder diagnosis, and published the results in the Annals of Internal Medicine in 2024.

People newly prescribed semaglutide had lower rates of medical encounters for tobacco use disorder than those starting any of seven other diabetes medicines, with hazard ratios ranging from about 0.68 against insulin to about 0.88 against other GLP-1 drugs. They also received fewer smoking cessation prescriptions and counselling sessions, which fits with less need for them.

Health record studies cannot measure whether anyone actually stopped smoking, and people prescribed semaglutide may differ in ways the analysis could not capture. Randomized trials of semaglutide in smokers without diabetes were registered from 2022 onward, and their results will say far more than any database study.

Is the weight gained after quitting worse than continuing to smoke?

Not even close

The weight gained after quitting does not come close to cancelling the heart benefit of stopping. Clair and colleagues followed 3,251 adults in the Framingham Offspring Study and published the analysis in JAMA in 2013. Among adults without diabetes, those who had quit within the past four years had a cardiovascular event rate 53 percent lower than current smokers, despite a median weight gain of 2.7 kg. Long term quitters had a 54 percent lower rate.

Adjusting for the weight gain barely changed those results. That is the context for any GLP-1 conversation here. The aim of managing post quit weight is to remove a reason people give for not quitting or for relapsing, not to suggest the weight is the bigger health problem. The cardiovascular article on this site covers GLP-1 heart outcome trials separately.

Where does a low dose GLP-1 protocol fit into a quit attempt?

A reasonable question, not a tested answer

No trial has tested a microdose or low dose GLP-1 protocol for smoking cessation or post quit weight, so any role is a hypothesis for a prescriber to weigh. Both published trials used standard doses: exenatide 2 mg weekly and dulaglutide 1.5 mg weekly. Whether a smaller dose would still blunt post quit weight gain is unknown.

The logic that makes people ask is easy to follow. Post quit weight gain comes mostly from appetite, and it builds over a few months. A gentler dose may cause less nausea, which matters because varenicline also causes nausea in roughly 25 to 30 percent of users. These practical points are worth raising with a healthcare provider, not acting on alone.

What is still unknown about GLP-1 medicines and smoking?

Gaps worth naming

The biggest open question is whether any GLP-1 medicine raises long term quit rates in people who are not already on a strong quit aid. The exenatide trial was positive but small and short. The dulaglutide trial was larger and neutral. Semaglutide and tirzepatide, which act more strongly on appetite and cross into the brain in different ways, have not yet reported randomized smoking results.

Vaping and other nicotine products are another gap. Almost all of the evidence comes from cigarette smokers, and nobody has studied whether GLP-1 medicines change nicotine use from e-cigarettes or pouches. Dose is the third. Every result in this article comes from standard doses, and a microdose may behave differently on both cravings and weight.

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