PHARMACOLOGICAL MECHANISMS AND CLINICAL EFFICACY OF GLP-1 RECEPTOR AGONISTS IN APPETITE REGULATION AND GLYCEMIC CONTROL: A SYSTEMATIC REVIEW IN OBESE PATIENTS WITH INSULIN RESISTANCE

Abstract

Background: Obesity and insulin resistance represent global health challenges with limited effective pharmacological options. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a promising therapy due to their effects on satiety, weight loss, and glycemic regulation.

Objective: To systematically evaluate the pharmacological mechanisms and clinical efficacy of GLP-1 RAs in appetite regulation and glycemic control among obese patients with insulin resistance.

Methods: This systematic review was conducted in accordance with PRISMA 2020 guidelines. Searches across PubMed, Scopus, Embase, Web of Science, and Google Scholar identified randomized controlled trials, crossover trials, and relevant mechanistic studies published between 2010 and 2024. Eleven eligible studies were included, encompassing pediatric, adolescent, and adult populations.

Results: GLP-1 RAs demonstrated significant reductions in BMI and body weight, with semaglutide achieving up to 16% reductions in adolescents and liraglutide reducing BMI in children as young as 7 years. HbA1c improvements were robust, particularly with dulaglutide and liraglutide in type 2 diabetes. Beyond metabolic effects, GLP-1 RAs improved eating behavior, reduced caloric intake, and delayed gastric emptying. Gastrointestinal side effects were the most common adverse events but were generally mild and transient.

Conclusion: GLP-1  receptor agonists represent an effective and well-tolerated therapy for obesity and insulin resistance, offering dual benefits in appetite regulation and glycemic control. Their role in pediatric and adult care highlights their potential to transform obesity management, though further research on long-term outcomes, cost-effectiveness, and personalized applications is warranted.