Jimmy Wen, BA
Medical Student
California Northstate University College of Medicine
Elk Grove, California, United States
Denise Nadora, BS
Medical Student
California Northstate University College of Medicine
Elk Grove, California, United States
Alina Truong, BS
Medical Student
California Northstate University College of Medicine
Elk Grove, California, United States
Ethan Bernstein, BS
Medical Student
California Northstate University College of Medicine
Elk Grove, California, United States
Christiane How-Volkman, MS
Medical Student
California Northstate University College of Medicine
Elk Grove, California, United States
Adam Razick, n/a
Student
University of California, Los Angeles
Los Angeles, California, United States
Daniel Razick, BS
Medical Student
California Northstate University College of Medicine
Elk Grove, California, United States
Muhammad Karabala, MS
Medical Student
California Northstate University College of Medicine
Elk Grove, California, United States
Eldo Frezza, MD
Assistant Dean of Research Professor of Surgery Surgery Clerkship Director
California Northstate University College of Medicine
Elk Grove, California, United States
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are currently at the forefront of type 2 diabetes mellitus (T2DM) and obesity treatment development and usage. However, recent focus on targeting more than one receptor such as glucose-dependent insulinotropic polypeptide (GIP) and glucagon (Gcg) receptors has been investigated to assess for improved glycemic control, weight loss, and safety profile.
Design:
A PubMed search was conducted to find relevant articles over the last 10 years regarding GLP-1 RA, dual agonist GLP-1/GIP, dual agonist GLP-1/Gcg, and triple agonist clinical trials and recent developments. A narrative review was conducted to examine the GLP-1/GIP/Gcg receptors and the current literature on the associated dual and triple agonists.
Results:
Several dual GLP-1/GIP RAs are currently in development, with the GIP receptor assisting GLP-1 in modulating central and peripheral pathways to prompt weight loss by increasing lipolysis and fat oxidation. Tirzepatide is at the forefront of this class, producing superior glycemic control and weight loss compared to GLP-1 RAs. Dual GLP-1/Gcg is another novel investigation by utilizing the Gcg receptor which increases energy expenditure by stimulating glucose production, fat oxidation, and mobilization of energy stores to promote weight loss. Triple agonism of GLP-1/GIP/Gcg is still mainly being investigated in clinical trials, but preliminary results show similar if not improved glycemic control and weight loss. However, despite the multi-agonist approach, gastrointestinal adverse events do not seem to be mitigated compared to traditional GLP-1 RAs.
Conclusions: The current literature shows promising results for the efficacy of dual and triple agonism of GLP-1/GIP/Gcg receptors. There are also several clinical trials being conducted across different dual and triple agonisms. Further research should focus on direct comparative studies between current GLP-1 RAs against these multi-receptor agonist agents.
