People who type "GLP-1 vs GLP-3" usually want to know whether the new drug beats Ozempic or Wegovy. The honest answer needs three drugs, not two, because the step from GLP-1 to "GLP-3" passes through tirzepatide. This page puts the three main obesity trials side by side, with the dose, the duration and the source next to every number.
What "GLP-3" means
Your gut makes GLP-1 and GLP-2. It makes no GLP-3.
The name comes from forums and sellers, who counted the receptors retatrutide activates and borrowed the GLP-1 brand for the total. Retatrutide (Eli Lilly, code LY3437943) is one peptide that activates the GIP, GLP-1 and glucagon receptors, described in Cell Metabolism in 2022.
Our sister site traces where the label came from in what GLP-3 peptide really refers to.
"GLP-1" in the question means the single agonists, above all semaglutide from Novo Nordisk (Wegovy for obesity, Ozempic for type 2 diabetes). Tirzepatide from Eli Lilly (Zepbound, Mounjaro) sits in between with two receptors.
It is not a GLP-3. Retatrutide has no brand name yet, and Lilly plans to file it with the FDA in early 2027.
Side effects, the price of each added receptor
The side effects are of the same kind on all three drugs: nausea, diarrhea, vomiting and constipation, mostly mild to moderate and concentrated while the dose goes up. What changes is how many people stop: at the top dose, 4.5% on semaglutide (gastrointestinal events only; 0.8% on placebo), 6.2% on tirzepatide (2.6%) and 11.3% on retatrutide (4.9%), the "Stopped for side effects" line of the table at the top of this page.
Retatrutide also brings two signals the GLP-1 drugs do not show at this rate: a heart rate increase that rose with the dose and peaked at 24 weeks in phase 2, and dysesthesia, a tingling or burning skin sensation, reported in phase 3. The full list, dose by dose, is in GLP-3 side effects and retatrutide side effects.
The most common adverse events in the retatrutide groups were gastrointestinal; they were dose-related, were mostly mild to moderate in severity, and were partially mitigated with a lower starting dose.
Jastreboff et al., NEJM 2023, phase 2 obesity trial abstract
Why this comparison has limits
- No trial has put GLP-1 and "GLP-3" head to head in obesity. Lilly has registered one against semaglutide in type 2 diabetes (TRANSCEND-T2D-2, NCT06260722), with no result published.
- The trials lasted 48 to 80 weeks and enrolled different people, so part of each gap is design, not drug.
- The STEP 1 dropout figure counts gastrointestinal events only, which makes it a floor.
- Retatrutide's phase 3 numbers are topline announcements, not yet full papers.
Doses in the trials
Every retatrutide arm used a once-weekly injection, raised step by step: 1 to 12 mg in phase 2, maintenance at 4, 9 or 12 mg in phase 3. The escalation schedules are laid out on our dosing site, Retatrutide Dose, as the trials ran them. They are trial protocols, not instructions.
What the numbers support
In their own trials, more receptors meant more people leaving because of side effects. Semaglutide and tirzepatide are approved medicines with a label.
Retatrutide is not. Outside a clinical trial, what circulates is research material, not the trial product.
For the side effects behind those dropouts, see the dropout table of every phase 3 trial.
