GLP-1 receptor agonist

From Retapedia, the free peptide encyclopedia

How do GLP-1 receptor agonists work?

GLP-1 receptor agonist — Peptide drugs that mimic glucagon-like peptide-1 to boost insulin secretion, slow gastric emptying, and cut appetite. Approved for type-2 diabetes and obesity.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of peptide drugs that mimic the endogenous incretin hormone glucagon-like peptide-1. Endogenous GLP-1 is secreted by intestinal L-cells in response to food intake and acts on pancreatic beta cells to enhance glucose-dependent insulin secretion. It also suppresses glucagon release, slows gastric emptying, and reduces appetite via central receptors in the hypothalamus and area postrema.

Therapeutic use

GLP-1 RAs are a mainstay of type-2 diabetes treatment and have become a leading drug therapy for obesity. They produce clinically meaningful weight loss (typically 10–20% of body weight on the highest-dose agents) and improvements in HbA1c, cardiovascular risk markers, and several non-diabetic conditions.

Pharmacology

Native GLP-1 has a half-life of approximately two minutes due to rapid cleavage by the enzyme dipeptidyl peptidase-4. Marketed GLP-1 RAs are engineered for resistance to DPP-4: exenatide is a synthetic exendin analogue, liraglutide adds a fatty-acid chain that promotes albumin binding, and semaglutide further modifies the sequence to extend its half-life to roughly one week.

Newer multi-agonists combine GLP-1 activity with agonism at the glucose-dependent insulinotropic polypeptide (GIP) and glucagon receptors. Tirzepatide is a dual GLP-1/GIP agonist; retatrutide is a triple GLP-1/GIP/glucagon agonist in late-stage trials.

“Natty” classification

Approved GLP-1 RAs such as semaglutide and tirzepatide are not on the 2026 WADA prohibited list, the edition in force until 31 December 2026, and WADA’s 2027 edition, published in September 2026 and in force from 1 January 2027, keeps them off. They are generally considered compatible with natural-bodybuilding standards when used under prescription for a recognised medical indication; federation rules on other uses vary, so check the sanctioning body’s own list.

An investigational agent is treated differently. Retatrutide has no regulatory approval anywhere, so it is prohibited at all times under WADA category S0 (non-approved substances).

Catalogued GLP-1 agonists on Retapedia

Ozempic Natty
Reduces appetite and slows digestion for 15-21% weight loss. Improves blood sugar control. Lowers heart attack and stroke risk by 20%.
Tirzepatide Natty
Dual GIP/GLP-1 agonist. Reduces appetite for up to 21% weight loss. Improves blood sugar and diabetes control. First drug approved for obstructive sleep apnea. GI side effects common.
Retatrutide Not natty
Triple agonist that curbs appetite and raises energy expenditure for 24% weight loss. Improves blood sugar, lowers blood pressure, and normalizes liver fat. Investigational; not FDA-approved.
5-Amino-1MQ Not natty
Oral small-molecule NNMT inhibitor that raises NAD+ and S-adenosyl methionine to boost fat-cell energy expenditure. Studied only in rodents for fat loss; no human trials exist.
MOTS-c Not natty
Mitochondrial-derived peptide that activates AMPK to improve insulin sensitivity and reproduce exercise-like metabolic adaptations in preclinical models. Investigational and WADA-banned; no approved human use.
NAD+ Natty
Boosts cellular energy production and DNA repair. Activates longevity enzymes. Improves metabolism and mitochondrial health. Cellular benefits proven, human longevity unproven.
Tesamorelin Not natty
Stimulates growth hormone release, lowering visceral abdominal fat and triglycerides. FDA-approved for HIV-associated lipodystrophy. Daily subcutaneous injection; fat reaccumulates when stopped.

See also

External links

Categories: Appetite | Weight Loss | Metabolism

This page was last updated on October 5, 2026, at 00:00 (UTC).

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