Molecular Pharmacology of Glucagon-Like Peptide 1-Based Therapies in the Management of Type Two Diabetes Mellitus and Obesity

Abdullah M Alzahrani,1– 3 Ghada A Alshobragi,1 Abdullah M Alshehri,1 Majed S Alzahrani,1 Hasan A Alshehri,1 Rami M Alzhrani,4 Samah Basudan,5 Ayed A Alkatheeri,6 Salman A Almutairi,7 Yahya A Alzahrani2,6 1Pharmaceutical Care Department, Ministry of National Guard—Health Affairs, Jeddah, 22384, Saudi Arabia; 2King Abdullah International Medical Research Center, Jeddah, 21423, Saudi Arabia; 3College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, 22384, Saudi Arabia; 4Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Taif University, Taif, 21944, Saudi Arabia; 5Department of Pharmacy, King Abdullah Medical Complex, Ministry of Health, Jeddah, Saudi Arabia; 6Drug Information Center, Department of Pharmacy, East Jeddah Hospital, Ministry of Health, Jeddah, 23816, Saudi Arabia; 7General Administration of Medical Services, Jeddah Medical Center, Jeddah, Saudi ArabiaCorrespondence: Yahya A Alzahrani, Drug Information Center, Department of Pharmacy, East Jeddah hospital, Ministry of health, Jeddah, 23816, Saudi Arabia, Tel +966557700178, Email [email protected]: The global increase in type 2 diabetes mellitus (DM2) and obesity presents a significant public health challenge, as these interconnected conditions contribute to severe complications, including cardiovascular disease, stroke, and certain cancers. The incretin system, particularly glucagon-like peptide-1 (GLP-1), has emerged as a promising therapeutic target due to its role in glycemic control and weight management.Objective: This review explores the molecular pharmacology of GLP-1 and its receptor agonists, evaluating their therapeutic efficacy in managing DM2 and obesity.Methods: A comprehensive literature review was conducted, analyzing recent advancements in GLP-1-based therapies, their mechanisms of action, and their clinical applications. The review also highlights the pharmacokinetic modifications developed to enhance the stability and efficacy of GLP-1 receptor agonists.Results: GLP-1 receptor agonists have demonstrated significant benefits in improving glycemic control, reducing body weight, and addressing metabolic complications. Novel therapeutic approaches, including dual and triple incretin receptor agonists, are showing enhanced efficacy in both diabetes and obesity management. However, challenges remain in optimizing treatment outcomes, addressing patient variability, and improving long-term adherence.Conclusion: GLP-1-based therapies have revolutionized the management of DM2 and obesity. Continued research is essential to refine these treatments, overcome existing limitations, and develop personalized approaches to maximize patient outcomes.Keywords: GLP-1 receptor agonists, type 2 diabetes mellitus, obesity management, incretin hormones, molecular pharmacology