GLP-1-based therapies for type 2 diabetes: from single, dual and triple agonists to endogenous GLP-1 production and L-cell differentiation

• Published in: Diabetology and metabolic syndrome Vol. 17; no. 1; pp. 60 - 27
• Main Authors: Movahednasab, Maedeh, Dianat-Moghadam, Hassan, Khodadad, Sana, Nedaeinia, Reza, Safabakhsh, Saeid, Ferns, Gordon, Salehi, Rasoul
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 17.02.2025; BioMed Central; BMC
• Subjects: Agonists; Apoptosis; Beta cells; Cardiovascular disease; Cell differentiation; Cell growth; Cell proliferation; Central nervous system; Cholecystokinin; Clinical trials; Dextrose; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes therapy; Dipeptidyl peptidase-4 inhibitors; Enteroendocrine L-cells; Food intake; Gastric emptying; GLP-1 receptor agonists; Glucagon; Glucagon-like peptide; Glucagon-like peptide 1; Glucose; Growth factors; Health aspects; Homeostasis; Hormones; Hyperglycemia; Hypoglycemic agents; Insulin resistance; Insulin secretion; Intestine; Kinases; Metabolism; Proteins; Review; Stem cells; Transcription factors; Type 2 diabetes; Type 2 diabetes mellitus; United Kingdom; Dipeptidyl peptidase-4 inhibitors; Enteroendocrine L-cells; Type 2 diabetes mellitus; GLP-1 receptor agonists; Glucagon-like peptide
• ISSN: 1758-5996; 1758-5996
• DOI: 10.1186/s13098-025-01623-w

Glucagon-like peptide-1 (GLP-1) is an incretin peptide hormone mainly secreted by enteroendocrine intestinal L-cells. GLP-1 is also secreted by α-cells of the pancreas and the central nervous system (CNS). GLP-1 secretion is stimulated by nutrient intake and exerts its effects on glucose homeostasis by stimulating insulin secretion, gastric emptying confiding the food intake, and β-cell proliferation. The insulinotropic effects of GLP-1, and the reduction of its effects in type 2 diabetes mellitus (T2DM), have made GLP-1 an attractive option for the treatment of T2DM. Furthermore, GLP-1-based medications such as GLP-1 receptor agonists and dipeptidyl peptidase-4 inhibitors, have been shown to improve diabetes control in preclinical and clinical trials with human subjects. Importantly, increasing the endogenous production of GLP-1 by different mechanisms or by increasing the number of intestinal L-cells that tend to produce this hormone may be another effective therapeutic approach to managing T2DM. Herein, we briefly describe therapeutic agents/compounds that enhance GLP-1 function. Then, we will discuss the approaches that can increase the endogenous production of GLP-1 through various stimuli. Finally, we introduce the potential of L-cell differentiation as an attractive future therapeutic approach to increase GLP-1 production as an attractive therapeutic alternative for T2DM.