Glucagon-like peptide 1 (GLP1) is an incretin hormone crucial for glucose metabolism. In healthy individuals, GLP1 is secreted by L-cells in the intestine in response to food ingestion.
This hormone has several important effects:
- Increased Insulin Secretion: GLP1 stimulates insulin secretion by pancreatic beta cells in response to elevated blood glucose levels.
- Suppression of Glucagon Secretion: It inhibits glucagon release from pancreatic alpha cells, thereby reducing glucose production by the liver.
- Slowing Gastric Emptying: GLP1 slows gastric emptying, enabling a more gradual absorption of glucose into the bloodstream.
- Increased Satiety: It promotes a feeling of satiety, helping to reduce food intake.
In patients with type 2 diabetes (T2D), the response to GLP1 is impaired, contributing to deregulation of blood glucose levels.
Due to the short half-life of native GLP1, GLP1 receptor agonists (GLP1RAs) have been developed to mimic the effects of GLP1 with longer durations of action. These GLP1RAs vary in chemical structure, pharmacokinetics (absorption, distribution, metabolism and excretion) and size, leading to differences in their clinical effects.
CLINICAL EFFECTS OF GLP1RAs
GLP1RAs help manage blood glucose levels by increasing insulin secretion and suppressing glucagon release. They also promote weight loss by increasing satiety and slowing gastric emptying.
Clinical trials have shown that some GLP1RAs have positive effects on cardiovascular health and may reduce the risk of major cardiovascular events, such as heart attack and stroke, in patients with T2DM.
EMERGING USES OF GLP1RAs
GLP1RAs are also being studied to treat other lifestyle-induced conditions, such as:
- Obesity: Because of their ability to increase satiety and promote weight loss.
- Pre-diabetes: to potentially delay or prevent the onset of diabetes.
- Non-alcoholic fatty liver disease (NAFLD): where metabolic regulation is crucial.
Les GLP1RAs therefore represent a significant advance in the treatment of T2DM and other potential metabolic conditions. The variability of the clinical effects of different GLP1RAs underlines the importance of personalized medicine.
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Sources:
Glucagon-like peptide 1 in health and disease.
Andersen A, Lund A, Knop FK, Vilsbøll T.
Nat Rev Endocrinol. 2018 Jul;14(7):390-403.
doi: 10.1038/s41574-018-0016-2.