The Emerging Role of Dual GLP-1 and GIP Receptor Agonists in Glycemic Management and Cardiovascular Risk Reduction

Abstract

The incretin pathway is a self-regulating feedback system connecting the gut with the brain, pancreas, and liver. Its predominant action is on the postprandial glucose levels, with extraglycemic effects on fat metabolism and endovascular function. Of the two main incretin hormones released with food ingestion, the actions of glucagon-like peptide-1 (GLP-1) have been exploited for therapeutic benefit. However, little attention has been paid to glucose-dependent insulinotropic polypeptide (GIP) until the recent experimental introduction of dual agonists, or “twincretins”. Interestingly, simultaneous activation of both receptors is not only replicative of normal physiology, it seems to be an innovative way to enhance their mutual salubrious actions. In patients with type 2 diabetes, dual agonists can have powerful benefits for glucose control and weight reduction. Additionally, there is mounting evidence of their favorable cardiovascular impact, making them potentially appealing pharmacologic agents of choice in the future. Although we seem to be poised on the horizons of exciting new breakthroughs, much knowledge has yet to be gained before these novel agents are ready for prime time.

Keywords:

• type 2 diabetes
• incretins
• glucagon-like peptide-1
• glucose-dependent insulinotropic polypeptide

Disclosure

This article has been written independently and reflects solely the opinion of the authors without any potential conflict of interest. Prof. Ali A. Rizvi has nothing to disclose. Prof. Manfredi Rizzo is former Director, Clinical Medical & Regulatory Department, Novo Nordisk Europe East and South and has given lectures, received honoraria and research support, and participated in conferences, advisory boards and clinical trials sponsored by pharmaceutical industry including Amgen, AstraZeneca, Boehringer Ingelheim, Kowa, Eli Lilly, Meda, Mylan, Merck Sharp & Dohme, Novo Nordisk, Novartis, Roche Diagnostics, Sanofi and Servier. None of the above-mentioned companies had any role in the preparation of this paper, which has been written independently and without any financial or professional help.