Weight loss therapy and addiction: increased risk after bariatric surgery but reduced risk with GLP-1 receptor agonists.

Abstract

Background: Obesity is an increasing public health problem because of its high prevalence and associated morbidity and mortality. Two weight-loss strategies are currently used, either bariatric surgery or pharmacological therapy with glucagon-like peptide-1 receptor agonists (GLP-1RAs). Preclinical studies in rodents suggested an increased risk of additive disorders after bariatric surgery contrasting with a reduced risk with GLP-1RAs.

Methods: An extensive literature search to detect clinical studies that investigated the prevalence of addictive disorders (food addiction, alcohol abuse, smoking, cannabis, cocaine, opioid use) following bariatric surgery or GLP-1RA therapy in obese patients.

Results: In observational cohort studies, the prevalence of alcohol use disorder was twofold higher after > 2 years following surgery (eleven studies, mainly with gastric bypass) whereas it was reduced roughly by half with GLP-1RA therapy (five studies, mainly with semaglutide). Similar findings were reported with other addictive disorders. An addiction transfer from food addiction to other addictive disorders is hypothesized to explain the increased risk after bariatric surgery. Several mechanisms are proposed to explain the favorable findings reported with GLP-1RAs, i.e. effects on the dopamine reward pathway, central GABA (gamma-aminobutyric acid) release, negative emotional stress associated with food/drug restriction and/or neuronal inflammation.

Conclusion: Available data from observational cohort studies confirm an increased risk of addictive disorders following bariatric surgery, contrasting with a reduced risk with GLP-1RA therapy. Both physicians and patients should be informed of the higher risk post-surgery whereas available promising results with GLP-1RAs should be confirmed in ongoing dedicated randomized controlled trials before any official indication.