What are incretins and secretagogues in endocrinology?

From the Guidelines

Incretins and secretagogues are crucial components in the management of glucose metabolism, with incretins being gut hormones that stimulate insulin secretion in a glucose-dependent manner, and secretagogues being agents that directly stimulate insulin secretion from pancreatic beta cells, regardless of blood glucose levels. Incretins, such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), enhance insulin release when blood glucose levels are elevated, and medications that mimic incretin action, like GLP-1 receptor agonists, offer advantages of weight loss and lower hypoglycemia risk 1. Secretagogues, including sulfonylureas like glipizide, glyburide, and glimepiride, provide cost-effective glucose lowering but with a greater risk of hypoglycemia 1.

Key Differences and Similarities

• Incretins stimulate insulin release in a glucose-dependent manner, reducing the risk of hypoglycemia, whereas secretagogues stimulate insulin release regardless of blood glucose levels, increasing the risk of hypoglycemia.
• Medications that mimic incretin action, such as GLP-1 receptor agonists, are typically administered as subcutaneous injections, while secretagogues are usually taken orally.
• Both incretins and secretagogues are used in the management of type 2 diabetes, with the choice of medication depending on individual patient needs and characteristics.

Clinical Implications

• The use of incretin mimetics, such as GLP-1 receptor agonists, has been associated with weight loss and improved glycemic control, making them a valuable option for patients with type 2 diabetes 1.
• Secretagogues, such as sulfonylureas, are effective in lowering blood glucose levels but require careful monitoring to minimize the risk of hypoglycemia 1.
• The choice of medication should be individualized, taking into account factors such as patient lifestyle, medical history, and concomitant medications.

Recommendations

• For patients with type 2 diabetes, incretin mimetics, such as GLP-1 receptor agonists, are a recommended option for those who require weight loss and improved glycemic control, while secretagogues, such as sulfonylureas, are suitable for patients who require cost-effective glucose lowering 1.
• Patients should be educated on the proper use of these medications, including dosing, administration, and potential side effects, to ensure optimal glucose control and minimize the risk of hypoglycemia.

From the FDA Drug Label

Incretins, such as glucagon-like peptide-1 (GLP-1), enhance glucose-dependent insulin secretion and exhibit other antihyperglycemic actions following their release into the circulation from the gut The term incretins refers to a group of metabolic hormones that stimulate the release of insulin in response to meals, enhancing glucose-dependent insulin secretion.

• GLP-1 is an example of an incretin hormone. There is no information in the provided drug label about secretagogues. 2

From the Research

Definition and Function of Incretins

• Incretins are hormones released by nutrients from the GI tract, amplifying glucose-induced insulin release 3, 4, 5, 6, 7
• The two most important incretin hormones are glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) 3, 4, 5, 6, 7
• Incretins have a crucial role in maintaining normal islet function and glucose homeostasis 6

Effects of Incretins on Glucose Homeostasis

• Incretins stimulate insulin secretion from pancreatic beta cells and reduce glucagon secretion from pancreatic alpha cells 4, 5, 7
• GLP-1 inhibits glucagon release, prolongs gastric emptying, and leads to decreases in body-weight 3, 4, 5, 7
• Incretins have a glucose-dependent effect on insulin secretion, making them unlikely to cause low blood sugars (hypoglycemia) 5

Incretins in Disease States

• In patients with type 2 diabetes, the incretin effect is decreased, mainly due to loss of the GIP-regulated second phase of insulin secretion, and because of a decreased secretion of GLP-1 3, 7
• GLP-1 is still insulinotropic in type 2 diabetes, and this has led to the development of compounds that activate the GLP-1 receptor to improve insulin secretion 5, 7
• Alterations in secretion and/or action of incretin hormones may contribute to the deterioration of glycemic control in diabetic patients 6

Therapeutic Potential of Incretins

• Incretin-based glucose-lowering medications, such as GLP-1 receptor agonists and inhibitors of dipeptidyl peptidase-4 (DPP-4), have been developed to treat type 2 diabetes 5, 7
• GLP-1 receptor agonists, such as liraglutide, have been shown to reduce cardiovascular events and prolong life in high-risk patients with type 2 diabetes 7
• Incretins may also have a role in the treatment of obesity, as they have been shown to reduce appetite and food intake, leading to weight loss 7