DefinePK

Abstract

Background: Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is widely prescribed for obesity and type 2 diabetes mellitus due to its glucose-lowering and weight-reducing properties. Recent evidence suggests that GLP-1 analogs may influence thyroid function and mood regulation through their effects on the hypothalamic-pituitary-thyroid (HPT) axis and central neurotransmitter pathways. Objective: The study aimed to evaluate the effects of Liraglutide on thyroid-stimulating hormone (TSH) levels and depressive symptoms, exploring the interactions between the hypothalamic-pituitary-thyroid (HPT) axis, metabolic factors, and mental health. Study Design: Randomized controlled trial. Settings: Department of Dermatology, Isra University Hospital, Hyderabad, Pakistan. Duration: June 2024 to January 2025. Methods: 60 participants divided into three groups (n=20 each), randomized via the envelope method. Participants received Liraglutide in varying doses (0.6mg, 1.2mg, and 1.8mg), with or without exercise, over six months. TSH levels and depressive symptoms (PHQ-9) were assessed at baseline, three and six months. Results: TSH levels decreased significantly (p<0.05) with higher Liraglutide doses (1.8 mg) and exercise, showing a dose-dependent response. At baseline, group A subgroup (i) had a mean TSH level of 5.4±1.5mIU/L, decreasing to 4.8±3.2mIU/L, while subgroup (ii) saw a reduction from 5.5±1.98mIU/L to 4.5±2.04mIU/L. Comparable reductions were observed across other groups, with exercises enhancing the effects. Depression severity showed significant increases in some subgroups, but exercise mitigated these effects, highlighting its role in managing depressive symptoms. Conclusion: Liraglutide demonstrated a dose-dependent effect on TSH levels and variable impacts on depression. Combining Liraglutide with exercise yielded better outcomes, supporting its use as an adjunctive therapy in managing metabolic and mental health conditions.