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Updated: Jun 13, 2026

An In Ovo Model for Testing Insulin-mimetic Compounds
Published on: April 23, 2018
[New hypoglycemic agents in type 2 diabetes]
1Université de Nancy I et service de diabétologie, maladies métaboliques et maladies de la nutrition, hôpital Jeanne-d'Arc, CHU de Nancy, 54201 Toul BP 90303. b.guerci@chu-nancy.fr
Abstract:
New treatments of type 2 diabetes have been developed, especially with the use of the properties of incretins, gastrointestinal hormones involved in glucose homeostasis. GLP-1 is responsible for most incretin effect with a rate that increases within minutes after meal intake, suggesting that its secretion is initially triggered by the combination of endocrine and nervous signals. The effects of GLP-1 on insulin secretion and glucagon are observed only at high glucose levels (glucose-dependent effects). In the type 2 diabetes, the incretin effect is altered due to reduced plasma concentrations of GLP-1, but its activity is intact. There are two innovative therapeutic approaches aimed to restore the incretin effect in patients with type 2 diabetes: the agonists of GLP-1 receptors administered subcutaneously that replace the deficiency of GLP-1; and the DPP-4 inhibitors that can prolong the life of endogenous GLP-1 by reducing activity of the enzyme DPP-4 that degrades GLP-1, molecules offering the advantage of oral administration. Their effectiveness on the glucose metabolism is around 0.5 to 1.1% and 0.8 to 1.5% in reduction in HbAlc for DPP-4 inhibitors and agonists of GLP-1 receptors, respectively. Moreover these latter have extra pancreatic effects, particularly by reducing gastric emptying and control of satiety, resulting in a weight loss of 1.6 to 3.8 kg. Their tolerance is generally good especially for the DPP-4 inhibitors, whereas agonists in GLP-1 receptor often cause nausea or vomiting at the initiation of the therapy. However their effectiveness and long-term safety need to be evaluated.
Insights
New type 2 diabetes treatments leverage incretins like GLP-1. Therapies include GLP-1 receptor agonists and DPP-4 inhibitors, offering improved glucose control and potential weight loss, though long-term safety requires further study.
Area of Science:
- Endocrinology
- Pharmacology
- Metabolic Diseases
Background:
- Type 2 diabetes involves altered incretin effect, with reduced glucagon-like peptide-1 (GLP-1) concentrations.
- GLP-1 plays a crucial role in glucose homeostasis, with glucose-dependent insulin secretion and glucagon regulation.
- Existing incretin-based therapies aim to restore the diminished incretin effect in type 2 diabetes patients.
Purpose of the Study:
- To review novel therapeutic strategies for type 2 diabetes targeting the incretin system.
- To compare the efficacy and side effect profiles of GLP-1 receptor agonists and DPP-4 inhibitors.
- To assess the impact of these treatments on glycemic control, weight, and overall patient tolerance.
Main Methods:
- Review of current literature on incretin-based therapies for type 2 diabetes.
- Comparative analysis of subcutaneous GLP-1 receptor agonists and oral DPP-4 inhibitors.
- Evaluation of reported HbA1c reductions, weight changes, and adverse events.
Main Results:
- GLP-1 receptor agonists showed HbA1c reductions of 0.8-1.5% and significant weight loss (1.6-3.8 kg) due to reduced gastric emptying and satiety control.
- DPP-4 inhibitors demonstrated HbA1c reductions of 0.5-1.1% with generally good tolerance.
- GLP-1 receptor agonists were associated with gastrointestinal side effects like nausea and vomiting, particularly upon initiation.
Conclusions:
- Both GLP-1 receptor agonists and DPP-4 inhibitors represent effective strategies for managing type 2 diabetes by enhancing the incretin system.
- GLP-1 receptor agonists offer additional benefits of weight loss, while DPP-4 inhibitors provide oral administration convenience and better initial tolerance.
- Further research is necessary to fully establish the long-term effectiveness and safety profiles of these innovative incretin-based treatments.
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