Cigarette smoking is the leading preventable cause of premature death worldwide. However smoking is a very difficult addiction to break whereby main reasons for not quitting or relapsing after cessation are the nicotine withdrawal syndrome and post-cessational weight gain. GLP-1 analogues are well known to stimulate insulin secretion and to reduce energy intake and therefore body weight. Recent findings from animal and human studies suggest a role of GLP-1 in the pathophysiology of addiction. The putative role of GLP-1 analogues in nicotine reward regulation combined with its weight reducing effects might be of major interest in view of novel pharmacotherapeutic options for smoking cessation.

• Substudy "fMRI": This substudy is to evaluate effects of Dulaglutide treatment on functional neuronal changes in smokers who want to quit smoking.
• Substudy "Energy": This substudy is to investigate the effect of Dulaglutide (Trulicity®) on REE and further parameters associated with energy metabolism (bodycomposition, haemodynamic parameters and catecholamine action) in a subset of patients recruited for the main trial.

Cigarette smoking is the leading preventable cause of premature death worldwide. However smoking is a very difficult addiction to break and despite established smoking cessation programs quit rates are low, especially in the real-life setting. The main reasons for not quitting or relapsing after cessation are the nicotine withdrawal syndrome and post-cessational weight gain. GLP-1 analogues are well known to stimulate insulin secretion and to reduce energy intake and therefore body weight. Recent findings from animal and human studies suggest a role of GLP-1 in the pathophysiology of addiction. The putative role of GLP-1 analogues in nicotine reward regulation combined with its weight reducing effects might be of major interest in view of novel pharmacotherapeutic options for smoking cessation.

• Substudy "fMRI" (60 patients): Supposing that GLP-1 and analogues modulates nicotine induces reward system this substudy is to analyze if treatment with Dulaglutide (Trulicity®) attenuates craving and therefore functional brain activation. It is to evaluate effects of Dulaglutide treatment on functional neuronal changes in smokers who want to quit smoking.
• Substudy "Energy" (60 patients): The aim of the substudy "Energy" is to investigate the effect of Dulaglutide (Trulicity®) on REE and further parameters associated with energy metabolism (bodycomposition, haemodynamic parameters and catecholamine action) in a subset of patients recruited for the main trial.

Inclusion Criteria for the main study:

• Age 18 to 75 years
• Daily smokers who are willing to quit and exhibit one of the following criteria: ≥10 cigarettes per day or
• At least moderate nicotine dependence defined by a Fagerstroem Score of ≥5 Points or
• Tobacco associated disease
• Treatment with varenicline (Champix®)

Additional Inclusion Criteria for the "substudy fMRI":

• Only patients aged 18-50 years are eligible

Additional Inclusion Criteria for the "substudy Energy":

• BMI of 18-30 kg/m2

Exclusion Criteria for the main study:

• Pregnancy (incl. wish to become pregnant within next 3 months) or breast feeding
• Pre-existing Treatment with GLP-1 agonists
• History of pancreatitis
• Severe renal insufficiency (estimated glomerular Filtration rate smaller than 30 ml/min/1.73 m2)
• Instable psychiatric conditions
• Anorexia nervosa

Additional Exclusion Criteria for the "substudy fMRI":

• Medical conditions that affect brain function (e.g. stroke, epilepsy, space occupying lesions, multiple sclerosis, Parkinson's disease, dementia, transient ischemic attack),
• Current use of medications that alter brain function
• Current illicit drug abuse including marijuana (alcohol ≤ 1 drink per day allowed)
• Claustrophobia, cardiac pacemaker, electronic device or ferromagnetic metal foreign bodies