The pharmaceutical industries are always on enthusiastic spirit while targeting GPCRs and it is the most sought biological target. Majority of the drugs that exist in market targets the GPCRs. Recently, there has been a huge interest to use it to   control Diabetes as an oral therapy. The availability of X-ray crystal structures has led to recent various attempts to design an oral therapy against diabetes.  

Glucagon-like peptide 1 (GLP-1) is a prime example, and has been exploited pharmacologically.  Even though the GLP-1 mimetics are available in injectables, the development of an oral formulation is    challenging to the drug designers. Computationally designing an antagonist to any   target   requires a meticulous straightforward approach. But designing an agonist to modulate any disease is very complicated and will undergo various failures.

Summary of the natural ligands, targets and actions of example GPCRs located in intestinal and pancreatic endocrine cells:

Recently FDA has approved the oral anti-diabetic drug semaglutide which act as an agonist against diabetes. It has paved the future way for the   drug designers and how the GPCRs are important. The GLP1 agonist Tirzepatide is in phase III clinical trials and the preliminary data support its efficacy to reduce sugar.

The hunt for an oral agonist that mimics the physiology has brought up high expectations as the most promising therapeutic approach to improve insulin sensitivity. The challenges of   designing drug that mimics GPCRs in pancrease will need to   cover the adverse reactions that occurs and the promiscuous nature of the selected drug candidates for further evaluation. The therapies targeting GLP-1 receptors are already having an impact on people with   Type-2 diabetes. We are witnessing tremendous progresses made recently in the understanding of the structure–function relationships that facilitated GPCRs drug development in diabetes.