Glucagon-like peptide 1 receptor agonists and mental health: A systematic review and meta-analysis

TY - JOUR

T1 - Glucagon-like peptide 1 receptor agonists and mental health: A systematic review and meta-analysis

AU - Pierret, Aureliane

AU - Mizuno, Yuya

AU - Saunders, Pippa

AU - Lim, Eshaya

AU - De Giorgi, Riccardo

AU - Howes, Oliver

AU - McCutcheon, Robert

AU - McGowan, Barbara

AU - Sen Gupta, Piya

AU - Smith, Daniel

AU - Ismail, Khalida

AU - Pillinger, Toby

PY - 2025/2/25

Y1 - 2025/2/25

N2 - ImportancePeople with obesity and diabetes mellitus have poorer psychiatric and cognitive outcomes and lower quality of life (QoL) compared to those without. Glucagon-like peptide 1 receptor agonists (GLP1-RAs) are treatments for diabetes and obesity which may also influence psychiatric outcomes.Objective To conduct a meta-analysis of randomised placebo-controlled trials to evaluate psychiatric, cognitive, and QoL outcomes with GLP1-RA treatment.Data sourcesWe searched MEDLINE, Embase, PsycINFO, and CENTRAL databases until 24/06/2024.Study selection Double-blind placebo-controlled trials comparing GLP1-RA to placebo in adults with overweight/obesity and/or diabetes, reporting on psychiatric, cognition, or quality of life outcomes, were included. Data extraction and synthesis Data extraction was performed in parallel by two reviewers. Random-effects meta-analysis was performed. Effect size measures were log risk ratios (log(RR)) and standardised mean differences (Hedges’ g). Quality of studies was appraised using the Cochrane risk-of-bias tool (RoB2). Certainty of evidence was assessed via GRADEpro.Main outcomes and measuresMain outcomes were risk of psychiatric adverse events (serious and non-serious); and change in mental health symptom severity, health-related quality of life, and cognition. FindingsWe included 80 randomised controlled trials in the meta-analysis, including 107,860 patients. GLP1-RA treatment was not associated with a significant difference in risk of serious (log(RR)=-0.02 [95%CI -0.20–0.17], p=0.87) and non-serious (log(RR)=-0.03 [95%CI -0.21 – 0.16], p=0.76) psychiatric adverse events, or depressive symptom change (g=0.02 [95%CI -0.51–0.55], p=0.94), compared to placebo. GLP1-RA treatment was associated with improvements in restrained eating (g=0.35 [95%CI 0.13–0.57], p=0.002) and emotional eating behaviour (g=0.32 [95%CI 0.11–0.54], p=0.003), and in mental health QoL (g=0.15 [95%CI 0.07 – 0.22], p<0.001), physical health QoL (g=0.20 [95%CI 0.14–0.26], p<0.001), diabetes-related QoL (g=0.23 [95%CI 0.15–0.32], p<0.001) and weight-related QoL (g=0.27 [95%CI 0.18–0.35], p<0.001) compared to placebo. Conclusions and relevance In patients with overweight/obesity and/or diabetes mellitus, GLP1-RA treatment is not associated with increased risk of psychiatric adverse events or worsening depressive symptoms relative to placebo, and is associated with improvements in QoL, restrained eating and emotional eating behaviour. These findings provide reassurance regarding the psychiatric safety profile of GLP1-RAs and suggest that GLP1-RA treatment contributes to both physical and emotional well-being.

AB - ImportancePeople with obesity and diabetes mellitus have poorer psychiatric and cognitive outcomes and lower quality of life (QoL) compared to those without. Glucagon-like peptide 1 receptor agonists (GLP1-RAs) are treatments for diabetes and obesity which may also influence psychiatric outcomes.Objective To conduct a meta-analysis of randomised placebo-controlled trials to evaluate psychiatric, cognitive, and QoL outcomes with GLP1-RA treatment.Data sourcesWe searched MEDLINE, Embase, PsycINFO, and CENTRAL databases until 24/06/2024.Study selection Double-blind placebo-controlled trials comparing GLP1-RA to placebo in adults with overweight/obesity and/or diabetes, reporting on psychiatric, cognition, or quality of life outcomes, were included. Data extraction and synthesis Data extraction was performed in parallel by two reviewers. Random-effects meta-analysis was performed. Effect size measures were log risk ratios (log(RR)) and standardised mean differences (Hedges’ g). Quality of studies was appraised using the Cochrane risk-of-bias tool (RoB2). Certainty of evidence was assessed via GRADEpro.Main outcomes and measuresMain outcomes were risk of psychiatric adverse events (serious and non-serious); and change in mental health symptom severity, health-related quality of life, and cognition. FindingsWe included 80 randomised controlled trials in the meta-analysis, including 107,860 patients. GLP1-RA treatment was not associated with a significant difference in risk of serious (log(RR)=-0.02 [95%CI -0.20–0.17], p=0.87) and non-serious (log(RR)=-0.03 [95%CI -0.21 – 0.16], p=0.76) psychiatric adverse events, or depressive symptom change (g=0.02 [95%CI -0.51–0.55], p=0.94), compared to placebo. GLP1-RA treatment was associated with improvements in restrained eating (g=0.35 [95%CI 0.13–0.57], p=0.002) and emotional eating behaviour (g=0.32 [95%CI 0.11–0.54], p=0.003), and in mental health QoL (g=0.15 [95%CI 0.07 – 0.22], p<0.001), physical health QoL (g=0.20 [95%CI 0.14–0.26], p<0.001), diabetes-related QoL (g=0.23 [95%CI 0.15–0.32], p<0.001) and weight-related QoL (g=0.27 [95%CI 0.18–0.35], p<0.001) compared to placebo. Conclusions and relevance In patients with overweight/obesity and/or diabetes mellitus, GLP1-RA treatment is not associated with increased risk of psychiatric adverse events or worsening depressive symptoms relative to placebo, and is associated with improvements in QoL, restrained eating and emotional eating behaviour. These findings provide reassurance regarding the psychiatric safety profile of GLP1-RAs and suggest that GLP1-RA treatment contributes to both physical and emotional well-being.

M3 - Article

SN - 2168-622X

JO - JAMA Psychiatry

JF - JAMA Psychiatry

ER -