2020/03/16 by Ricardo J. Samms, Matthew P. Coghlan, Kyle W. Sloop · 5 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Diabetes Treatment and Management #Metabolism, Diabetes, and Cancer #Pharmacology and Obesity Treatment
paper · pdf · doi:10.1016/j.tem.2020.02.006
openalex publication_date 2020/03/16 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
Glucagon-like peptide-1 (GLP-1) receptor agonists improve glucose homeostasis, reduce bodyweight, and over time benefit cardiovascular health in type 2 diabetes mellitus (T2DM). However, dose-related gastrointestinal effects limit efficacy, and therefore agents possessing GLP-1 pharmacology that can also target alternative pathways may expand the therapeutic index. One approach is to engineer GLP-1 activity into the sequence of glucose-dependent insulinotropic polypeptide (GIP). Although the therapeutic implications of the lipogenic actions of GIP are debated, its ability to improve lipid and glucose metabolism is especially evident when paired with the anorexigenic mechanism of GLP-1. We review the complexity of GIP in regulating adipose tissue function and energy balance in the context of recent findings in T2DM showing that dual GIP/GLP-1 receptor agonist therapy produces profound weight loss, glycemic control, and lipid lowering.