Semaglutide, Tirzepatide and Retatrutide are each a copy of the gut hormone GLP-1.
GLP-1 is what your gut releases after a meal to tell your brain you have eaten.
The difference is reach: Semaglutide acts on 1 receptor, Tirzepatide acts on 2 receptors and Retatrutide acts on 3 receptors. More receptors has generally meant more effect, and more side effects.
| Comparison | Semaglutide Ozempic · Wegovy | Tirzepatide Mounjaro · Zepbound | Retatrutide LY3437943 · reta |
|---|---|---|---|
| How it works | How it works Semaglutide copies a single gut hormone, GLP-1. That one target is enough to change how hungry you feel, how fast your stomach empties, and how your body handles sugar after a meal. | How it works Tirzepatide is one molecule that fits two different receptors, GLP-1 and GIP. Adding the second target is what separates it from semaglutide. | How it works Retatrutide adds a third target, glucagon, to the two tirzepatide already hits. Glucagon is the interesting one, because it does something the others do not. |
| What it is | The drug in Ozempic and Wegovy: a weekly shot that curbs hunger for steady weight loss. | The drug in Mounjaro and Zepbound: a weekly shot for major weight loss and blood sugar. | An experimental weekly shot with some of the biggest weight-loss numbers yet in trials. |
| Status | FDA approvedFDA-approved | FDA approvedFDA-approved | In trialsInvestigational |
| Typical dose | 0.25–2.4 mg per week | 2.5–15 mg per week | 1–12 mg per dose |
| How often | Weekly | Weekly | Weekly |
| Stays active | About 1 week | About 5 days | About 6 days |
| Dose comes from | FDA drug label | FDA drug label | Clinical trial protocol |
| Cycled? | Not cycled Published human study | Not cycled Published human study | Not cycled in the trials Clinical trial protocol |
| What it does | |||
| Drug class | GLP-1 agonist | GLP-1 / GIP agonist | GLP-1/GIP/glucagon agonist |
| Used for | People use it to lose weight and steady their blood sugar. It calms appetite and cravings so you feel full sooner and eat less without white-knuckling it. | People use it for major weight loss and better blood sugar. It works on two gut-hormone signals at once to reduce hunger, and tends to produce larger losses than older options. | People follow it for very large weight loss, around a quarter to nearly a third of body weight in trials. It acts on three appetite and metabolism pathways at once. |
| Receptors hit | GLP-1 | GLP-1, GIP | GLP-1, GIP, glucagon |
| Numbers | |||
| Full dose line | 0.25 up to 2.4 mg per week (start low, increase slowly) | 2.5 up to 15 mg per week (start low, increase slowly) | 1 up to 12 mg per dose (start low, increase slowly) |
| Why that cycle | Taken continuously, with the dose stepped up rather than paused. In the STEP 1 extension people regained about two thirds of the weight they had lost within a year of stopping. The question is whether to stay on it, not when to take a break. | Taken continuously. In SURMOUNT-4, people who kept taking it lost a further 5.5 percent over the following year while those switched to placebo gained 14 percent back. Stopping is the thing that undoes it. | Given continuously for the whole study period: TRIUMPH-1, 80 weeks with an extension to 104. The dose is stepped up at the start, which is a ramp rather than a cycle, and no trial in this class built in a planned break. |
| Weight / effect | ~15% body weight lost | ~20% body weight lost | ~24% body weight lost |
| Chain length | 31 residues | 39 residues | 30 residues |
| Common vial | 5 mg | 10 mg | 10 mg |
| Before you start | |||
| Route | Under the skin (also comes as a pill) | Under the skin (subcutaneous) | Under the skin (subcutaneous) |
| Do not use if | A personal or family history of medullary thyroid cancer, or the genetic condition MEN 2 Pregnancy, or trying to become pregnant A history of pancreatitis, which needs a conversation with your doctor first Severe stomach-emptying problems (gastroparesis) | A personal or family history of medullary thyroid cancer, or the genetic condition MEN 2 Pregnancy, or trying to become pregnant A history of pancreatitis, which needs a conversation with your doctor first Severe stomach-emptying problems (gastroparesis) | Not legally available outside clinical trials, so no prescriber is assessing whether it suits you Pregnancy, or trying to become pregnant |
What separates them
Proof behind the dose. Semaglutide and Tirzepatide have doses taken straight off FDA drug labels. Retatrutide has a dose from a clinical trial protocol.
What doesn't differ: They are all taken the same way (under the skin), aimed at the same thing (weight loss) and on the same schedule (weekly).
What people actually report
Semaglutide
- Nausea, diarrhea, and vomiting are the main side effects, usually worst in the first weeks and each time the dose goes up.
- Starting at a low dose and increasing slowly keeps them manageable.
- It carries a warning about a rare thyroid tumor risk.
- Severe stomach pain that spreads to your back, which can signal pancreas inflammation
- A lump or swelling in your neck, hoarseness, or trouble swallowing
Tirzepatide
- Nausea, diarrhea, and vomiting are common, mostly early on and each time the dose increases.
- Starting low and increasing slowly over several weeks keeps side effects milder.
- It carries a warning about a rare thyroid tumor risk.
- Severe stomach pain that spreads to your back
- A lump or swelling in your neck, hoarseness, or trouble swallowing
Retatrutide
- Stomach side effects like nausea and vomiting are the main issue.
- It must be increased slowly from a low dose over months, and it is not legally sold outside clinical trials.
- Severe stomach pain that spreads to your back
- Vomiting badly enough that you cannot keep fluids down
Side effects are what users and trials report most often, not a complete list. Anything sudden, spreading, or breathing-related is an emergency regardless of which compound caused it.
People also compare
This comparison does not cover cost, long-term safety, or how you personally will respond. Effect figures come from separate trials in different populations and are not always directly comparable to each other. Nothing here is medical advice or a recommendation to use any of these. Talk to a clinician about your own situation.