Glucagon-Like Peptide-1: Physiology and What Research Reports

What Glucagon-Like Peptide-1 Is

Glucagon-like peptide-1 (GLP-1) is an endogenous peptide hormone — that is, a signalling molecule the body makes itself, not a compound that had to be invented in a laboratory. It belongs to the group of gut hormones called incretins, which are released in response to nutrients arriving in the intestine. A 2024 primer in Current Biology described the GLP-1 receptor as a class B G protein-coupled receptor through which GLP-1 links nutrient intake to insulin secretion and to central signals affecting food intake (PMID 39626623).

Readers usually meet the term in one of two very different contexts. The first is physiology: GLP-1 as a hormone studied in humans and animals. The second is pharmacology: the GLP-1 receptor agonist medicines that were engineered to activate the same receptor for far longer than the native hormone does, a class summarised in a clinical pharmacology review (PMID 31855395). Confusing the hormone with the drug class is the most common source of misunderstanding.

Where GLP-1 Is Produced and What It Does

The published descriptions of GLP-1 biology centre on a few tissue-level actions:

• Gut origin. The Current Biology primer described GLP-1 as a product of intestinal enteroendocrine cells that is released in response to nutrient intake (PMID 39626623).
• Pancreatic islets. The same primer described receptor activation as enhancing glucose-dependent insulin secretion (PMID 39626623).
• Stomach. A 2024 editorial in the British Journal of Anaesthesia discussed delayed gastric emptying as a recognised pharmacological effect of long-acting GLP-1 receptor agonists (PMID 38290907).
• Brain and appetite pathways. Central receptor signalling affecting food intake was described in the receptor primer (PMID 39626623).
• Lipid handling. A 2024 review in Diabetes & Metabolism Journal argued that GLP-1 should also be considered a regulator of lipid metabolism, summarising reported effects across intestine, liver and adipose tissue (PMID 38650100).

Hormone versus medicine

How GLP-1 Is Measured and Studied

Because the native hormone circulates briefly and at low concentrations, most of the clinical evidence base concerns receptor pharmacology and long-acting agonists rather than direct hormone administration. Broadly, four research approaches appear in the cited literature:

1. Receptor and molecular pharmacology, describing how ligands engage the receptor (PMID 39626623).
2. Mechanistic and metabolic reviews, collating tissue-level findings such as those reported for lipid metabolism (PMID 38650100).
3. Clinical pharmacology summaries of the approved agonist class and its monitoring considerations (PMID 31855395).
4. Pharmacoepidemiology, in which large health-records cohorts are analysed for adverse event signals, as in a 2023 JAMA research letter that compared users of GLP-1 receptor agonists prescribed for weight loss with users of a non-incretin weight-loss agent (PMID 37796527).

Gastrointestinal and Other Adverse Events: What Studies Report

Adverse-event data in this field come almost entirely from the medicine class, not from the endogenous hormone.

Gastrointestinal events. In the 2023 JAMA analysis, researchers reported an increased risk of pancreatitis, gastroparesis, bowel obstruction and biliary disease among people dispensed GLP-1 receptor agonists for weight loss relative to the comparator group (PMID 37796527). The study was observational, so the authors framed the findings as risk signals to inform counselling rather than as causal proof.

Perioperative concerns. Delayed gastric emptying raised questions about residual gastric contents and pulmonary aspiration during anaesthesia, an issue set out in a 2024 British Journal of Anaesthesia discussion of long-acting agonists (PMID 38290907). A 2025 multidisciplinary consensus statement from the Society for Perioperative Assessment and Quality Improvement was published to give clinicians structured guidance on assessing and managing patients taking these medicines before procedures (PMID 40379536).

Skin and hair. A 2025 review in Skin Appendage Disorders catalogued dermatologic implications reported in association with GLP-1 receptor agonist use, including cutaneous and hair-related changes accompanying substantial weight reduction (PMID 41058954).

Cancer questions. A 2026 Nature Cancer article examined the relationship between GLP-1 medicines and cancer, describing both the mechanistic rationale for interest and the limits of current human data (PMID 41545715).

Discontinuation

A 2025 JAMA article addressed discontinuation of GLP-1 receptor agonists, discussing how often treatment stops and what clinicians should consider when it does (PMID 39535741). Discontinuation is a distinct research question from efficacy, and it is one reason the literature increasingly treats these agents as long-term rather than short-course therapies.

Where the Literature Is Still Developing

Several fields have begun publishing on GLP-1 biology outside diabetes and obesity medicine:

• Inflammatory bowel disease. A 2025 review in the Journal of Crohn's & Colitis examined proposed mechanisms, clinical implications and therapeutic potential of GLP-1 receptor agonists in IBD (PMID 40972535).
• Reproductive medicine. A 2024 Fertility and Sterility article discussed treating obesity and fertility in the era of GLP-1 receptor agonists (PMID 38810863).
• Dermatology. A 2025 JAMA Dermatology paper examined GLP-1 receptor agonists in hidradenitis suppurativa (PMID 40802272).

Why the Term Matters to Readers of Peptide Literature

GLP-1 is one of the clearest examples of a naturally occurring peptide hormone whose receptor became a major drug target. For readers working through peptide literature, three distinctions repeatedly matter: whether a paper studied the endogenous hormone or an engineered agonist; whether findings came from a randomised trial, an observational database or a mechanistic model; and whether a claimed effect was measured in humans at all. Reviews of the receptor and of the agonist class make those distinctions explicit (PMID 39626623, PMID 31855395).

This page is for educational purposes only and is not medical advice; consult a licensed physician about any medical condition, medication or treatment decision. PeptideU summarises published research and does not recommend or supply any compound.

References

• Glucagon-like peptide-1 receptor (Current Biology, 2024)
• Glucagon-Like Peptide-1: New Regulator in Lipid Metabolism (Diabetes & Metabolism Journal, 2024)
• Glucagon-Like Peptide-1 Receptor Agonists (2026)
• Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss (JAMA, 2023)
• Perioperative management of long-acting glucagon-like peptide-1 (GLP-1) receptor agonists: concerns for delayed gastric emptying and pulmonary aspiration (British Journal of Anaesthesia, 2024)
• Perioperative management of patients taking glucagon-like peptide 1 receptor agonists: SPAQI multidisciplinary consensus statement (British Journal of Anaesthesia, 2025)
• Dermatologic Implications of Glucagon-Like Peptide-1 Receptor Agonist Medications (Skin Appendage Disorders, 2025)
• Glucagon-like peptide-1 medicines and cancer (Nature Cancer, 2026)
• Discontinuation of Glucagon-Like Peptide-1 Receptor Agonists (JAMA, 2025)
• Glucagon-like peptide-1 (GLP-1) receptor agonists in inflammatory bowel disease: mechanisms, clinical implications, and therapeutic potential (Journal of Crohn's & Colitis, 2025)
• Treating obesity and fertility in the era of glucagon-like peptide 1 receptor agonists (Fertility and Sterility, 2024)
• Glucagon-Like Peptide-1 Receptor Agonists in Hidradenitis Suppurativa (JAMA Dermatology, 2025)