The role of incretins in diabetes and obesity treatment

Incretin hormones are intestinally derived hormones stimulating glucose-dependent insulin secretion in response to food intake. Incretin hormones play an important role in glucose homeostasis.

The first incretin hormone identified was gastric inhibitory polypeptide (GIP), which is also referred to as glucose-dependent insulinotropic polypeptide. In the early 1980s, glucagon-like peptide (GLP1) was discovered as a proglucagon cleavage product produced in intestinal L cells.

GLP-1 is an incretin hormone with multiple glucoregulatory actions, including enhancement of glucose-dependent insulin secretion, suppression of inappropriately elevated glucagon secretion, slowing of gastric emptying, and reduction of food intake and body weight. Postprandial secretion of GLP-1 is reduced in patients with type 2 diabetes, suggesting that the GLP-1 signaling pathway is an attractive therapeutic target. However, GLP-1 is rapidly degraded by the enzyme dipeptidyl peptidase-IV and has a relatively short half-life.

The therapeutic potential of the GLP-1 pathway has led to the development of a class of compounds that share several glucoregulatory actions with GLP-1 but are resistant to dipeptidyl peptidase-IV degradation.

GLP-1 receptor agonists provide significant improvements in HbA1c, and this class of drugs also helps to decrease the risk of hypoglycemia and promote weight loss. Several drugs in the class have shown positive results in cardiovascular outcome trials in diabetes and most recently also in obesity. 

Incretin research at Profil

 Profil was involved into the development of numerous GLP-1 receptor agonists over the last 15 years and Profil services supported several new GLP-1 drug developments from the early phase clinical trials up to marketing authorization.
Based on this specific experience Profil is now involved in new drug developments exploring the synergistic metabolic benefits of simultaneous modulation of e.g. glucagon, GLP-1 and GIP receptors through a single-molecule. These novel dual-acting peptides have the potential to be an effective pharmacological approach targeting obesity and diabetes.

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Dr. Hans de Vries

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