Semaglutide and Liraglutide Significantly Cut Weight in Mental Illness Patients with Obesity; Semaglutide Shows Largest Effect.

Obesity is highly prevalent in individuals with mental illness, particularly those with schizophrenia spectrum disorders, often exacerbated by antipsychotic medications. This comorbidity significantly increases the risk of metabolic complications like type 2 diabetes and cardiovascular disease, leading to poorer quality of life and reduced life expectancy. Current weight management strategies often fall short in this vulnerable population, highlighting an urgent need for effective and safe pharmacological interventions. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are potent metabolic regulators, but their comparative efficacy and safety specifically for weight management in mental illness patients remained unclear.

This network meta-analysis synthesized data from nine randomized controlled trials, involving 595 participants (average age 37.8 years, 55.3% female, 83.9% with schizophrenia spectrum disorders). The study evaluated the comparative risk-benefit profiles of GLP-1RAs for obesity comorbid with mental illness. Treatment arms included subcutaneous exenatide (BID/QW), subcutaneous liraglutide (QD), and subcutaneous semaglutide (QW), compared against a control group (placebo, k=8; non-placebo, k=1). The primary endpoint was body weight, with secondary outcomes including BMI, waist circumference, various blood-based metabolic markers, blood pressure, and adverse events.

Subcutaneous semaglutide (QW) demonstrated the largest estimated effect, significantly reducing body weight compared to control with a standardized mean difference of -2.101 (95% CI: -2.978 to -1.224). Subcutaneous liraglutide (QD) also significantly reduced body weight, showing a standardized mean difference of -0.945 (95% CI: -1.784 to -0.106) versus control. Beyond weight, S-LIR(QD) was associated with reductions in waist circumference and HbA1c levels. While S-LIR(QD) led to lower incidences of serious adverse events (SAEs), it was linked to higher incidences of nausea, vomiting, and constipation compared to control. Similarly, S-SEM(QW) significantly reduced BMI, waist circumference, fasting plasma glucose (FPG), and HbA1c levels, but also resulted in higher incidences of nausea, vomiting, and constipation. Notably, neither drug significantly differed from control regarding other measured outcomes, including psychiatric hospitalization or changes in overall schizophrenia symptoms.