Mental health outcomes in obesity interventions with GLP-1 receptor agonists: is it similar to other obesity interventions? A narrative review with systematic evidence synthesis

Obesity is a chronic condition with multifaceted biological, psychosocial, and behavioral factors. While its cardiometabolic implications are well-documented, the bidirectional relationship between obesity and mental health disorders—such as anxiety, depression, and eating disorders—remains underexplored in obesity intervention research. This narrative review aims to synthesize the psychological effects of lifestyle, pharmacological, and surgical interventions in obesity treatment, emphasizing the role of glucagon-like peptide-1 (GLP-1) receptor agonists due to their increasing prevalence and mental health safety concerns.

A comprehensive literature review was conducted utilizing MEDLINE, Embase, and Cochrane databases, focusing on meta-analyses, systematic reviews, and clinical trials published up to June 2025. The review included studies assessing psychological outcomes in individuals undergoing lifestyle modifications, pharmacotherapy, or bariatric surgery, addressing mental health domains such as quality of life, anxiety, depression, and suicidality.

Behavioral interventions consistently reported no adverse effects on mental health, with modest improvements observed in depression and mental health-related quality of life. Bariatric surgery was linked to short-to-medium-term reductions in depressive and anxiety symptoms; however, long-term benefits appeared diminished, with some studies indicating increased suicidality after five years. Pharmacotherapies, including orlistat, bupropion/naltrexone, and phentermine/topiramate, exhibited mixed psychiatric effects. Notably, GLP-1 receptor agonists (Semaglutide, liraglutide, Tirzepatide) demonstrated improvements in self-reported mental wellbeing across several trials. Initial pharmacovigilance data suggested a potential association with suicidality, yet subsequent robust cohort studies and meta-analyses have discredited this link.

The evidence indicates that mental health is a critical, yet often overlooked, component of obesity management. Most weight loss interventions appear to be psychologically safe or beneficial; however, long-term data, particularly regarding GLP-1 receptor agonists, remain scarce. Future randomized trials should prioritize mental health outcomes, and individualized treatment strategies must incorporate psychological support to enhance long-term results. This review provides a comparative summary of the mental health outcomes associated with various obesity interventions.

Year: 2026

Reference: Osborne, D., & Abdelgadir, E. (2026). Mental health outcomes in obesity interventions with GLP-1 receptor agonists: Is it similar to other obesity interventions? A narrative review with systematic evidence synthesis. International Journal of Obesity, 1-9. https://doi.org/10.1038/s41366-025-02002-1

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