The incretin peptides are among the most clinically validated signaling molecules in modern medicine. This profile explains the incretin system, decodes the GLP research series, and covers the mechanism of GLP-1 receptor agonism.
What you’re actually reading about: decoding the GLP series
The GLP research compounds correspond to the three landmark incretin agonists driving today’s metabolic science. If you’ve seen these in the headlines, here’s the translation:
- GLP-1-S — commonly known as semaglutide: a single GLP-1 receptor agonist.
- GLP-2-T — commonly known as tirzepatide: a dual GLP-1 / GIP receptor agonist.
- GLP-3-R — commonly known as retatrutide (often shortened to “Reta”): a triple GLP-1 / GIP / glucagon receptor agonist.
Each step up the series engages one additional receptor — and represents a distinct generation of incretin research.
The incretin effect
After a meal, the gut releases hormones — chiefly GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide) — that amplify insulin release from the pancreas. This “incretin effect” sits at the center of metabolic research.
Receptor agonism
A GLP-1 receptor agonist binds and activates the GLP-1 receptor, engaging glucose-dependent insulin signaling, gastric emptying, and central satiety pathways. Characterizing these mechanisms has become one of the most productive areas in all of peptide science.
Single, dual, and triple agonism
The progression from single to triple agonism is the story of the field’s last decade. Semaglutide (GLP-1-S) targets the GLP-1 receptor alone. Tirzepatide (GLP-2-T) adds the GIP receptor, engaging two incretin pathways at once. Retatrutide (GLP-3-R) adds a third — the glucagon receptor — which is why it’s described as a triple agonist. Each added target is a separate lever on metabolism, and comparing them head-to-head is now an active area of research.
Clinical outlook
Few peptide mechanisms are as thoroughly tested in humans. Semaglutide has completed landmark Phase 3 cardiovascular-outcomes research (the SELECT trial, NCT03574597). Tirzepatide has advanced through the large SURPASS and SURMOUNT Phase 3 programs across metabolic disease. And retatrutide, the newest of the three, is now in Phase 3 — including a dedicated obesity program (NCT07232719) and a head-to-head study against tirzepatide (NCT06662383). Researchers are also pushing incretin science well beyond metabolism — into cardiovascular, liver, and neurological questions — making this one of the most closely watched frontiers in translational medicine.
Frequently asked questions about GLP-1 & Incretin Peptides
Straight answers to the questions researchers most often ask. Everything below summarizes published preclinical and clinical literature; it is not medical advice, and these compounds are supplied for laboratory research only.
What is a GLP-1 receptor agonist?
A GLP-1 receptor agonist is a peptide that mimics glucagon-like peptide-1, a gut hormone released after eating that stimulates insulin, suppresses glucagon, slows gastric emptying and reduces appetite. Semaglutide is the best-known example.
What is the difference between semaglutide, tirzepatide and retatrutide?
They differ in how many receptors they target. Semaglutide activates the GLP-1 receptor only; tirzepatide is a dual GLP-1/GIP agonist; retatrutide is a triple GLP-1/GIP/glucagon agonist. Each additional receptor has, in trials, been associated with greater weight reduction. Our GLP-1-S, GLP-2-T and GLP-3-R research compounds correspond to these three.
What is GLP-3-R?
GLP-3-R is our catalog name for the retatrutide research compound — a triple GIP/GLP-1/glucagon receptor agonist currently in Phase 3 trials. The "3" refers to the three receptors it targets.
Is retatrutide FDA approved?
No. Retatrutide is investigational and in Phase 3 development. Semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound) are FDA-approved as prescription medicines; the research compounds sold here are not those products and are for laboratory use only.
How much weight loss has been reported with tirzepatide versus semaglutide?
In the SURMOUNT-5 head-to-head trial, tirzepatide produced greater average weight reduction than semaglutide over 72 weeks; in earlier Phase 3 programs tirzepatide reached roughly 20% and semaglutide roughly 15% mean body-weight reduction at the highest doses. Retatrutide reached about 24% at 48 weeks in Phase 2.
What is the half-life of semaglutide, tirzepatide and retatrutide?
All three are engineered for once-weekly administration in clinical use: semaglutide's half-life is about one week, tirzepatide's about five days, and retatrutide's roughly six days. The long half-lives come from fatty-acid side chains that bind albumin.
What side effects are reported for GLP-1 agonists in trials?
The most common are gastrointestinal — nausea, vomiting, diarrhea and constipation — typically during dose escalation. Trials also monitor for gallbladder events, pancreatitis and, in rodents, thyroid C-cell tumors, which is why the approved drugs carry a boxed warning.
References
- Mechanisms of action and therapeutic applications of GLP-1 and dual GIP/GLP-1 receptor agonists Incretin & GLP-1 receptor agonism
- GLP-1 receptor agonists in the treatment of type 2 diabetes - state-of-the-art Incretin & GLP-1 receptor agonism
- GLP-1 Receptor Agonists: Beyond Their Pancreatic Effects Incretin & GLP-1 receptor agonism
- Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes Semaglutide (GLP-1-S)
- Semaglutide for the treatment of obesity Semaglutide (GLP-1-S)
- Once-Weekly Semaglutide in Adults with Overweight or Obesity Semaglutide (GLP-1-S)
- Tirzepatide for Obesity Treatment and Diabetes Prevention Tirzepatide (GLP-2-T)
- Tirzepatide as Compared with Semaglutide for the Treatment of Obesity Tirzepatide (GLP-2-T)
- Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial Tirzepatide (GLP-2-T)
- Retatrutide-A Game Changer in Obesity Pharmacotherapy Retatrutide (GLP-3-R)
- Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial Retatrutide (GLP-3-R)
- Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: Rationale and design of the TRIUMPH registrational clinical trials Retatrutide (GLP-3-R)
