Glucagon-like peptide-1 analogues: a new way to quit smoking? (SKIP)—a structured summary of a study protocol for a randomized controlled study

Background Cigarette smoking is the leading preventable cause of premature death. Despite dedicated programmes, quit rates remain low due to barriers such as nicotine withdrawal syndrome or post-cessation weight gain. Glucagon-like peptide-1 (GLP-1) analogues reduce energy intake and body weight and seem to modulate addictive behaviour. These GLP-1 properties are of major interest in the context of smoking cessation. The aim of this study is to evaluate the GLP-1 analogue dulaglutide as a new therapy for smoking cessation. Methods This is a placebo-controlled, double-blind, parallel group, superiority, single-centre randomized study including 255 patients. The intervention consists of a 12-week dulaglutide treatment phase with 1.5 mg once weekly or placebo subcutaneously, in addition to standard of care (behavioural counselling and pharmacotherapy with varenicline). A 40-week non-treatment phase follows. The primary outcome is the point prevalence abstinence rate at week 12. Smoking status is self-reported and biochemically confirmed by end-expiratory exhaled carbon monoxide measurement. Further endpoints include post-cessational weight gain, nicotine craving analysis, glucose homeostasis and long-term nicotine abstinence. Two separate substudies assess behavioural, functional and structural changes by functional magnetic resonance imaging and measures of energy metabolism (i.e. resting energy expenditure, body composition). Discussion Combining behavioural counselling and medical therapy, e.g. with varenicline, improves abstinence rates and is considered the standard of care. We expect a further increase in quit rates by adding a second component of medical therapy and assume a dual effect of dulaglutide treatment (blunting nicotine withdrawal symptoms and reducing post-cessational weight gain). This project is of high relevance as it explores novel treatment options aimed at preventing the disastrous consequences of nicotine consumption and obesity. Trial registration ClinicalTrials.gov NCT03204396 . Registered on June 26, 2017.