Effect of liraglutide on depressive symptoms in overweight or obese patients with type 2 diabetes: protocol for a pilot randomized controlled trial

Abstract

Introduction: Patients with concurrent obesity, type 2 diabetes, and depression experience high disease severity and prevalence. This triad of conditions compromises quality of life and treatment adherence, further exacerbating disease progression. Therapeutic strategies for such patients must address both glycemic control and psychological well-being. Liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), offers benefits beyond glucose-lowering and weight reduction, with emerging evidence suggesting it may also alleviate depressive symptoms. Therefore, liraglutide represents a promising intervention for managing depression in patients with obesity and diabetes. Objectives: This study aims to assess the therapeutic efficacy of liraglutide in overweight or obese patients with type 2 diabetes and comorbid depression, with a specific focus on its antidepressant effects. Methods: This is a randomized, double-blind, placebo-controlled pilot trial. Sixty eligible participants will be randomly assigned (1:1) to receive either liraglutide (initiated at 0.6 mg/day, titrated weekly to a maximum of 1.8 mg/day) or a matched placebo, as an adjunct to standard care for 12 weeks. The primary endpoints include blood glucose levels, glycated hemoglobin, body mass index, Hamilton Depression Rating Scale score, and metrics derived from resting-state functional magnetic resonance imaging (resting-state fMRI). Secondary endpoints will assess changes in inflammatory biomarkers (tumor necrosis factor-α, interleukin-6), oxidative stress indicators (superoxide dismutase, malondialdehyde), homeostasis model assessment of insulin resistance, insulin sensitivity index, and homeostasis model assessment of β-cell function. Conclusions: This trial will provide preliminary data on the effects of liraglutide on depressive symptoms in overweight/obese patients with type 2 diabetes. The findings are expected to provide a basis and reference for subsequent large-scale clinical research.