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GLP-1: Hormone, Function & Medical Importance
GLP-1 (Glucagon-like Peptide-1) is a natural hormone that regulates blood sugar and plays a key role in the treatment of type 2 diabetes and obesity.
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GLP-1 (Glucagon-like Peptide-1) is a natural hormone that regulates blood sugar and plays a key role in the treatment of type 2 diabetes and obesity.
What is GLP-1?
GLP-1 (Glucagon-like Peptide-1) is an incretin hormone produced and released by specialised cells (L-cells) in the small intestine in response to food intake. It belongs to the group of gastrointestinal hormones and plays a central role in regulating blood glucose levels and the feeling of fullness (satiety). In modern medicine, GLP-1 serves as the basis for an important class of drugs used in the treatment of type 2 diabetes and obesity.
Mechanism of Action
GLP-1 exerts its effects through specific GLP-1 receptors found in various organs, including the pancreas, brain, heart, and gastrointestinal tract. Its key actions include:
- Stimulation of insulin secretion: GLP-1 stimulates the beta cells of the pancreas to release insulin – but only when blood glucose is elevated (glucose-dependent mechanism), which minimises the risk of hypoglycaemia (low blood sugar).
- Suppression of glucagon: GLP-1 inhibits the release of glucagon, a hormone that raises blood sugar levels.
- Slowing of gastric emptying: Food remains in the stomach longer, leading to a slower rise in blood glucose after meals.
- Appetite reduction: GLP-1 acts on the brain (particularly the hypothalamus) to promote an early feeling of fullness, reducing overall food intake.
- Cardioprotective effects: Studies demonstrate beneficial effects on the cardiovascular system, including reduced risk of heart attack and stroke in high-risk patients.
Medical Use and Application
Because natural GLP-1 is rapidly broken down by the enzyme DPP-4 (dipeptidyl peptidase-4) with a half-life of only 1–2 minutes, it cannot be used therapeutically in its native form. The pharmaceutical industry has therefore developed two drug classes that exploit the GLP-1 signalling pathway:
GLP-1 Receptor Agonists
These agents mimic the action of natural GLP-1 and are protected from enzymatic degradation by DPP-4. Well-known examples include semaglutide, liraglutide, dulaglutide, and exenatide. They are used to treat type 2 diabetes and – at higher doses – for weight management in obesity. Administration is typically via subcutaneous injection; an oral form of semaglutide is also available.
DPP-4 Inhibitors (Gliptins)
These medications prevent the breakdown of endogenous GLP-1 by the DPP-4 enzyme, thereby extending its duration of action. Examples include sitagliptin and saxagliptin. They have a milder effect compared to GLP-1 receptor agonists but offer a favourable side-effect profile.
Clinical Relevance in Type 2 Diabetes
In people with type 2 diabetes, GLP-1 secretion after a meal is often reduced – a phenomenon known as the incretin defect. GLP-1-based therapies can compensate for this deficit. These medications effectively lower the HbA1c level (long-term blood glucose marker) with a low risk of hypoglycaemia, since their insulin-stimulating effect is glucose-dependent.
GLP-1 in Obesity and Weight Management
GLP-1 receptor agonists have proven to be an effective therapeutic option for obesity. Through central appetite suppression and delayed gastric emptying, they lead to significant reductions in body weight. Clinical trials with semaglutide (e.g., the STEP trials) demonstrated average body weight reductions of 10–15%.
Side Effects
GLP-1-based therapies are generally well tolerated. Common side effects primarily affect the gastrointestinal tract:
- Nausea and vomiting (especially at the start of therapy)
- Diarrhoea or constipation
- Reduced appetite
Less common but noteworthy side effects include:
- Pancreatitis (inflammation of the pancreas) – in rare cases
- Gallbladder disease
- Possible loss of muscle mass with rapid weight loss
Contraindications exist for certain thyroid conditions (medullary thyroid carcinoma) and a personal or family history of this disease.
Research and Future Perspectives
GLP-1 research is advancing rapidly. Novel dual and triple receptor agonists (e.g., tirzepatide, which simultaneously activates GLP-1 and GIP receptors) demonstrate even stronger effects on blood glucose and body weight. GLP-1-based approaches are also being investigated for non-alcoholic fatty liver disease (NAFLD), heart failure, and potentially neurodegenerative conditions such as Parkinson's disease.
References
- Drucker DJ. - The biology of incretin hormones. - Cell Metabolism, 2006.
- Davies MJ et al. - Management of Hyperglycemia in Type 2 Diabetes, 2022. - American Diabetes Association / European Association for the Study of Diabetes (ADA/EASD) Consensus Report, Diabetes Care, 2022.
- Wilding JPH et al. - Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1 Trial). - New England Journal of Medicine, 2021.
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