GLP-1 has multiple effects, including enhancing insulin secretion from pancreatic beta cells in response to glucose, increasing insulin expression, preventing beta-cell apoptosis, promoting the formation of new beta cells, reducing glucagon secretion, slowing down stomach emptying, promoting satiety, and improving glucose disposal in peripheral tissues.

Due to these diverse effects, there has been significant interest in developing long-lasting agonists of the GLP-1 receptor (GLP-1R) for the treatment of type 2 diabetes (T2D).

[22] GLP1R neurons particularly and densely innervate stomach muscle and can communicate with additional organ systems changing breathing and heart rate due to activation.

[22] Upon binding to its ligand GLP-1, the GLP-1 receptor activates intracellular signaling pathways that regulate insulin secretion, glucose metabolism, and satiety.

The rise in cAMP activates protein kinase A (PKA), which promotes insulin exocytosis and enhances beta cell survival and proliferation.

Activation of the receptor delays the rate at which the stomach empties, leading to increased satiety and reduced food intake.

Activation of the GLP-1 receptor promotes feelings of satiety, leading to a reduction in food intake and improved weight management.

This delay in gastric emptying contributes to the feeling of fullness and aids in controlling postprandial blood glucose levels.

Some studies suggest that these agents may reduce the risk of cardiovascular events, such as heart attacks, strokes, and cardiovascular-related mortality.

They can be prescribed alongside other oral antidiabetic medications, such as metformin or sulfonylureas, to provide additional glycemic control and improve overall treatment outcomes.

One strategy used for overcoming this problem is by synthesising new GLP-1 receptor agonists with a prolonged circulating half-life that will display a reduced degradation by DPP-4 enzymes.

Commercially known as Ozempic (semaglutide), is a medication that belongs to a class of drugs called glucagon-like peptide-1 receptor agonists (GLP-1 RAs).

The starting dose is usually low and gradually increased over several weeks to help minimize potential gastrointestinal side effects, such as nausea.

The optimal dose for an individual is determined by their healthcare provider based on factors such as blood sugar levels, response to treatment, and tolerability.

The medication has shown significant reductions in HbA1c (a measure of long-term blood sugar control) as well as fasting and postprandial (after-meal) glucose levels.

Exendin-4, an FDA-approved antidiabetic glucagon-like peptide 1 (GLP-1) receptor agonist, has been tested in mice with the mutated human huntingtin protein showing neurodegenerative changes, motor dysfunction, poor energy metabolism, and high blood glucose levels.

Htt aggregation decreases beta cell mass and thus impairs insulin release and increases blood glucose levels.

It also increased insulin sensitivity by about 50%, improved insulin-stimulated glucose uptake, and protect pancreatic beta cell function.

In addition to its other effects on the Huntington's disease mouse model, daily treatment of Ex-4, the GLP-1R agonist, significantly delayed the onset of mortality and extended the lifespan by approximately one month.