ABSTRACT
Glucagon-like peptide-1 receptor agonists (GLP-1Ras) have been established as a treatment option for people with type 2 diabetes. Their use is also approved for chronic weight management of obesity and overweight. Ongoing evidence from bariatric surgical studies have suggested the important interplay between several gut hormones in ameliorating cardio-metabolic complications of obesity. This has led to the development of dual and triple agonists for the management of type 2 diabetes and obesity. These dual and triple agonists have been developed by using GLP-1RA as a backbone peptide because of its well-established mechanistic, pharmacodynamic, and safety profile. Most dual and triple peptide therapies are being investigated in phase 1 and phase 2 clinical trials with a few being in phase 3 clinical trials. Amongst them, tirzepatide, a GIPR (glucose-dependent insulinotropic polypeptide receptor)/GLP-1R dual peptide, exhibits an impressive efficacy in HbA1c and body weight reduction, raising its potential as a bridge between currently approved anti-obesity pharmacotherapy and bariatric surgery.
