From the FDA Drug Label
Teduglutide is an analog of naturally occurring human glucagon-like peptide-2 (GLP-2), a peptide secreted by L-cells of the distal intestine. GLP-2 is known to increase intestinal and portal blood flow and inhibit gastric acid secretion Teduglutide binds to the glucagon-like peptide-2 receptors located in intestinal subpopulations of enteroendocrine cells, subepithelial myofibroblasts and enteric neurons of the submucosal and myenteric plexus. Activation of these receptors results in the local release of multiple mediators including insulin-like growth factor (IGF)-1, nitric oxide and keratinocyte growth factor (KGF).
The MOA of GLP-2 agonist, such as teduglutide, is to bind to GLP-2 receptors in the intestine, leading to the release of various mediators that promote intestinal growth and absorption. However, the provided drug label does not directly address how GLP-2 agonists treat diabetes. 1
From the Research
GLP-2 agonists are not used to treat diabetes, as they primarily work by promoting intestinal growth and improving nutrient absorption in the gut, without significantly affecting blood glucose regulation, insulin secretion, or glucagon suppression. The mechanism of action of GLP-2 agonists, such as teduglutide, involves binding to GLP-2 receptors in the gastrointestinal tract, stimulating intestinal epithelial proliferation and reducing apoptosis, which helps improve intestinal function in conditions like short bowel syndrome 2. Unlike GLP-1 agonists, which are effective in improving glycemic control, promoting weight loss, and potentially offering cardiovascular benefits, GLP-2 agonists do not provide the metabolic benefits needed for diabetes management 3.
Key Points
- GLP-2 agonists, such as teduglutide, are used to treat short bowel syndrome, not diabetes
- They work by promoting intestinal growth and improving nutrient absorption in the gut
- GLP-2 agonists do not significantly affect blood glucose regulation, insulin secretion, or glucagon suppression
- For diabetes treatment, physicians should consider GLP-1 receptor agonists, which have proven efficacy in improving glycemic control and promoting weight loss 4, 5, 6
Therapeutic Use
The main therapeutic use of GLP-2 agonists is for short bowel syndrome, where they increase intestinal villus height, crypt depth, and nutrient absorption, reducing the need for parenteral support 3. In this context, teduglutide has been shown to be effective in improving fluid absorption and reducing parenteral nutrition requirements 6. However, for diabetes management, GLP-1 receptor agonists are the preferred choice due to their metabolic benefits 2.