Tirzepatide and Smoking: What the Research Says About Nicotine Cravings and Weight Gain After Quitting

Many people who smoke say that the fear of gaining weight is one of the reasons they have not quit, and that fear has a basis in data, because most people who stop smoking gain some weight during the first year. Researchers have also noticed that GLP-1 based medications appear to act on the same brain reward circuits that drive nicotine craving, an observation that has prompted a series of clinical trials, including a new multisite study of tirzepatide that began in 2026.

This article explains what is known about tirzepatide, nicotine and weight after quitting, where the evidence is still thin, and how people taking tirzepatide can approach quitting with their clinician. It is educational information rather than medical advice. Tirzepatide is not FDA approved as a smoking cessation treatment, and no published randomized trial has yet shown that tirzepatide helps people quit.

Why do people gain weight after they quit smoking?

People gain weight after quitting smoking mainly because nicotine suppresses appetite and slightly raises the number of calories the body burns, and both effects fade once nicotine is gone. Published research suggests that nicotine raises resting energy expenditure by several percent in regular smokers while dampening hunger signals, so after quitting, food tends to taste better, meals get larger and snacking often replaces the hand to mouth habit of smoking.

The Aubin meta analysis in the BMJ pooled 62 studies and estimated an average weight gain of about 1.1 kg at one month, 2.9 kg at three months and 4.7 kg at twelve months among people who quit without medication.

Averages hide a wide spread of outcomes, because in the same analysis about 16 percent of quitters lost weight while about 13 percent gained more than 10 kg.

Is the weight gain worth the health benefit of quitting?

Large cohort studies suggest that the health benefit of quitting smoking far outweighs the risk from typical weight gain after quitting. A 2013 analysis of the Framingham Offspring Study in JAMA by Clair and colleagues found that recent quitters had roughly half the risk of cardiovascular events seen in people who kept smoking, and adjusting for weight gain did not meaningfully change that result.

Weight gain still matters, especially for people with type 2 diabetes or obesity, because a temporary rise in blood sugar has been reported in the first few years after quitting. For that reason, some clinicians see value in approaches that address smoking and weight at the same time.

How might GLP-1 medications affect nicotine cravings?

GLP-1 receptors are present in brain areas involved in reward and motivation, including the ventral tegmental area and the nucleus accumbens, and animal studies suggest that activating these receptors blunts the dopamine surge that nicotine produces. In rodent experiments, GLP-1 receptor agonists reduced nicotine self administration and nicotine induced dopamine release, which is the reward signal that reinforces smoking.

Tirzepatide activates GIP receptors in addition to GLP-1 receptors. Whether the added GIP activity changes its effect on cravings is unknown, and no completed human trial has yet examined tirzepatide and nicotine.

What have GLP-1 smoking cessation trials shown so far?

Human trials of GLP-1 medications for smoking cessation have produced mixed results, with one positive exenatide trial, one dulaglutide trial that showed no difference in quit rates and several supportive observational studies.

Exenatide. In the 2021 trial by Yammine and colleagues in JAMA Network Open, 84 adults with prediabetes or overweight received weekly exenatide or placebo alongside nicotine patches for six weeks. Seven day abstinence at six weeks was about 46 percent with exenatide and about 27 percent with placebo, and the exenatide group reported fewer cravings and gained roughly 5 pounds less weight.

Dulaglutide. A 2023 trial by Lengsfeld and colleagues in eClinicalMedicine randomized 255 adults to dulaglutide or placebo on top of varenicline and counseling. Quit rates were nearly identical at 12 weeks, about 64 percent in each group, although participants taking dulaglutide gained less weight than those on placebo.

Semaglutide. A 2024 study in the Annals of Internal Medicine, based on health records from people with type 2 diabetes, found that semaglutide was associated with fewer medical encounters for tobacco use disorder than other diabetes medications, and a 2025 randomized trial of semaglutide in alcohol use disorder reported fewer cigarettes per day among participants who smoked. Neither study was designed to test smoking cessation directly.

What is the tirzepatide smoking cessation trial testing?

A randomized trial of tirzepatide for smoking cessation, registered as NCT07602699, began recruiting in June 2026 at four academic centers: the University of Southern California, Yale University, the University of Chicago and the University of Colorado Anschutz. The trial plans to enroll 300 adults with overweight or obesity who want to quit and will assign them to tirzepatide or placebo, both with nicotine patches, for 16 weeks within a 24 week study.

Tirzepatide in the trial starts at 2.5 mg weekly and rises to 10 mg, and researchers will measure abstinence, cigarettes per day, weight gain after quitting and cardiovascular risk factors, with primary completion expected in March 2028. A case report in the Primary Care Companion for CNS Disorders also described a patient who stopped smoking abruptly after starting tirzepatide because cigarettes began to taste and smell unpleasant, although a single case cannot establish cause and effect.

Can someone take tirzepatide while they are still smoking?

People can take tirzepatide while they still smoke, because no direct drug interaction between tirzepatide and nicotine or tobacco smoke is known. Tirzepatide is a peptide broken down by ordinary protein processing rather than by the liver enzyme CYP1A2, which tobacco smoke speeds up, so smoking is not expected to change tirzepatide blood levels.

Smoking does add risks that overlap with some tirzepatide side effects. Nicotine relaxes the lower esophageal sphincter and can worsen reflux, which tirzepatide can also aggravate by slowing stomach emptying, and smoking is an independent risk factor for pancreatitis, which appears among the warnings for tirzepatide. Smoking also raises cardiovascular risk in ways that weight loss alone cannot offset.

How should people on tirzepatide combine it with quit smoking medications?

Tirzepatide can generally be used alongside standard smoking cessation treatments, but a few combinations call for closer attention from a prescriber.

Varenicline. Nausea is the most common side effect of varenicline, reported by about 30 percent of users in trials, and in SURMOUNT-1 nausea affected roughly 25 to 33 percent of tirzepatide users depending on dose. Starting both medications at once, or starting varenicline during a tirzepatide dose increase, may make nausea harder to tolerate, so some clinicians stagger the start dates.

Nicotine replacement. Patches, gum, lozenges and sprays have no known interaction with tirzepatide, although nicotine gum and lozenges can themselves cause hiccups, heartburn and mild nausea.

Bupropion. Bupropion also reduces appetite and lowers the seizure threshold, so severe vomiting or signs of electrolyte loss should be reported promptly, and prescribers usually review the whole medication list before combining drugs that affect appetite.

What practical steps help people quit smoking while on tirzepatide?

People who plan to quit smoking while taking tirzepatide tend to fare better when they coordinate the timing with their clinician, use a proven cessation aid and keep protein and fluid intake steady. Choosing a quit date during a period when the tirzepatide dose is stable, rather than during a dose increase, makes it easier to tell which medication is causing any new side effect.

Cochrane reviews suggest that behavioral support combined with medication improves the chance of staying quit compared with medication alone, and free state quitlines and text based programs offer that support. Adequate protein and regular activity help protect lean mass while appetite changes, and a weekly weight check gives a clearer picture than daily fluctuations.

The bottom line

GLP-1 research suggests a plausible link between these medications and nicotine reward, and an early exenatide trial showed encouraging results, but the overall evidence is mixed and tirzepatide has not yet been tested in a completed smoking cessation trial. People taking tirzepatide who want to quit should rely on proven cessation treatments and plan the timing with their clinician.