The incretin class
GLP-1, GIP, the pivotal trial numbers, and where research material sits against approved drugs.
Covered here: Semaglutide · Tirzepatide · Retatrutide · AOD-9604 · 5-amino-1MQ
GLP-1 is glucagon-like peptide-1, a hormone the gut releases after a meal. The incretin effect is the phenomenon it explains: glucose taken by mouth produces a larger insulin response than the same amount of glucose given by vein, because food in the intestine triggers hormone signalling that an infusion bypasses. GLP-1 and GIP are the two incretin hormones, and every drug in this class is built on their receptors.
A GLP-1 agonist is a molecule engineered to activate that receptor and to resist the enzyme that clears the natural hormone within minutes. Semaglutide acts at the GLP-1 receptor. Tirzepatide acts at both GLP-1 and GIP. Retatrutide adds glucagon to those two. That is the entire structural story of the class, and it is also why the question people actually ask, which one is best, has no clean answer: the trials were run in different populations, over different durations, against different comparators, and only the approved products were studied as products.
The published means from those trials are the most-quoted numbers in the field, and our incretin review carries each one with its trial, journal and year attached. The gap worth understanding is the one between a named trial of an approved product and a vial of research material carrying the same molecule name. The first has a dossier. The second has a certificate, at best, and a certificate speaks to what is in the vial, not to what was found in the trial.
Common questions
What is GLP-1?
GLP-1 is glucagon-like peptide-1, a 30-amino-acid hormone released by cells in the intestine after eating. It acts on the GLP-1 receptor and is broken down within minutes by the enzyme DPP-4, which is why the drug class built on it uses modified, longer-lasting molecules rather than the hormone itself.
What is the incretin effect?
The incretin effect is the observation that glucose taken by mouth triggers a substantially larger insulin response than the same quantity of glucose delivered intravenously. The difference is hormonal: food in the gut releases GLP-1 and GIP, which amplify the insulin response. Those two hormones are the incretins, and the effect is the reason the class exists.
What is a GLP-1 agonist, and which one is best?
A GLP-1 agonist is a molecule designed to activate the GLP-1 receptor and resist rapid enzymatic clearance. Best is not a question the published record answers, because the pivotal trials used different populations, durations and comparators, so the headline percentages are not directly comparable to each other. The approved products have dossiers behind them; research material carrying the same molecule name does not.
Do peptides work for weight loss?
One peptide class has deep human efficacy evidence for body weight, and it is the incretin class, studied as approved prescription drugs in large named randomised trials. Outside that class, most compounds marketed for fat loss have little or no published human efficacy data, and several have none at all. The honest answer is that the evidence is concentrated in one place rather than distributed across the category.
What is AOD-9604?
AOD-9604 is a 16-amino-acid analogue of the C-terminal region of human growth hormone, residues 177 to 191 with an added tyrosine, developed in the 1990s as a weight-loss candidate. It went through human clinical testing and was not approved for any indication. It is still marketed as a fat-loss peptide on the strength of preclinical work, which is exactly the extrapolation the rest of this site is about.
What is 5-amino-1MQ?
5-amino-1MQ is not a peptide. It is a small molecule that inhibits nicotinamide N-methyltransferase, an enzyme involved in nicotinamide metabolism, and the published work on it is preclinical: cell culture and mouse models. No human efficacy trial has been published, so any benefit attributed to it is an extrapolation from animal data.
Read the evidence
5 pieces on this subject, every finding attributed and every gap stated.
Related topics
For research use only · Not for human or veterinary use · No compound discussed here is FDA-approved for any indication