From the Guidelines
GLP-1 was discovered in the early 1980s through research on the proglucagon gene. The discovery of GLP-1 is attributed to the sequencing of mammalian proglucagon genes, which revealed that the proglucagon gene encodes multiple hormones, including GLP-1 1. Scientists were initially studying glucagon, a hormone that raises blood sugar, when they found that the proglucagon gene produced several distinct peptides through tissue-specific processing. In the pancreas, the gene produces glucagon, while in the intestine, it produces GLP-1. Further research revealed that GLP-1 is released from intestinal L-cells in response to food intake and has important effects on insulin secretion, gastric emptying, and appetite regulation.
Key Points
- The proglucagon gene was found to encode multiple hormones, including GLP-1 1
- GLP-1 is released from intestinal L-cells in response to food intake and has effects on insulin secretion, gastric emptying, and appetite regulation
- The discovery of GLP-1 led to the development of GLP-1 receptor agonists and DPP-4 inhibitors used to treat type 2 diabetes and obesity, as seen in recent studies such as the STEP trials which examined the efficacy of semaglutide 1
Discovery and Function
The breakthrough came when researchers sequenced mammalian proglucagon genes and identified that this single gene produced several distinct peptides through tissue-specific processing. This discovery was significant because it revealed a gut hormone that could stimulate insulin release in a glucose-dependent manner, meaning it only works when blood sugar is elevated. This property made GLP-1 particularly interesting for diabetes treatment, as it could lower blood glucose without causing dangerous hypoglycemia. Recent studies have continued to explore the effects of GLP-1, including its role in weight loss and cardiovascular risk reduction, with GLP-1 receptor agonists such as semaglutide and liraglutide showing promise in these areas 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Discovery of GLP-1
- The discovery of GLP-1 spans more than 30 years and includes contributions from multiple investigators 2
- GLP-1 is an incretin that plays important physiological roles in glucose homeostasis, produced from the intestine upon food intake, stimulating insulin secretion and keeping pancreatic β-cells healthy and proliferating 3
- The discovery that GLP-2 promotes mucosal growth in the intestine is described, and key findings from both preclinical studies and the GLP-2 clinical development program for short bowel syndrome (SBS) are reviewed 2
Key Findings and Developments
- Important attributes of GLP-1 action and enteroendocrine science are reviewed, with emphasis on mechanistic advances and clinical proof-of-concept studies 2
- GLP-1 analogs have demonstrated a potential in molecular imaging of pancreatic β-cells, which may be useful in early detection of the disease and evaluation of therapeutic interventions, including islet transplantation 3
- Novel therapeutic options for type 2 diabetes mellitus based on the action of the incretin hormone GLP-1 were introduced in 2005, with exenatide and liraglutide being available in many countries 4
Clinical Development and Applications
- GLP-1 receptor agonists have been developed, including exenatide, liraglutide, and other long-acting agents, which have demonstrated reductions in hemoglobin A1c, fasting blood glucose, and body weight 5, 4
- These agents have been shown to improve cardiovascular risk factors, including blood pressure, lipid parameters, and inflammatory markers 5
- GLP-1 receptor agonists are recommended as the preferred first injectable glucose-lowering therapy for type 2 diabetes, even before insulin treatment, due to their mechanism of action and safety profile 6