The 30-second summary
- The three leading molecules differ by how many gut-hormone receptors they activate: semaglutide (1), tirzepatide (2), retatrutide (3). Average weight loss rises with each: roughly 15% → 21% → up to 30%.
- Retatrutide is not available: it is in Phase 3 trials, years from a possible approval. Tirzepatide and semaglutide are what your prescriber can offer today.
- The right drug is rarely the one with the biggest trial number. It is the one you can get, tolerate, afford, and stay on, paired with the habits that protect your body while you lose.
The three drugs, in one paragraph
There are three molecules at the centre of the GLP-1 conversation, sold under several brand names:
- Semaglutide: Ozempic (diabetes) and Wegovy (weight). A single agonist: GLP-1 only.
- Tirzepatide: Mounjaro (diabetes) and Zepbound (weight). A dual agonist: GLP-1 + GIP.
- Retatrutide: no brand name yet, because it is not approved. A triple agonist: GLP-1 + GIP + glucagon.
Each added receptor has, so far, added weight loss. That is the simple story. The useful story has more in it.
The numbers, side by side
From the major trials (different trials, different populations, so this is a guide, not a head-to-head):
| Drug | Receptors | Average weight loss | Trial / duration |
|---|---|---|---|
| Semaglutide 2.4 mg | GLP-1 | ~15% | STEP 1, 68 weeks |
| Tirzepatide 15 mg | GLP-1 + GIP | ~21% | SURMOUNT-1, 72 weeks |
| Retatrutide 12 mg | GLP-1 + GIP + glucagon | ~24% (Phase 2, 48 wk); up to ~30% (TRIUMPH-1, 104 wk) | Phase 2 / TRIUMPH-1 |
The only direct head-to-head we have is tirzepatide versus semaglutide (SURMOUNT-5, 2025), where tirzepatide produced about 50% more average loss. Retatrutide has not been compared directly against either; its numbers come from separate trials, so the comparison above is indicative, not definitive.
Why "biggest number" is the wrong way to choose
A trial average describes a population. It does not describe you. In every one of these trials, the spread is wide: some women on semaglutide lose 25% of their body weight; some women on tirzepatide lose 8%. Genetics, baseline insulin sensitivity, sleep, protein intake, training, and how faithfully the dose is titrated all move the result more than the choice between two good drugs.
So the questions that actually decide your outcome are not "which has the highest trial number?" They are:
- What can I get? Retatrutide is not an option: it is not approved. Between semaglutide and tirzepatide, your insurance, your country, and your prescriber's judgement usually narrow it for you.
- What can I tolerate? The drug you can stay on beats the drug you quit because the nausea was unmanageable. Tolerance is individual.
- What can I afford, indefinitely? These are long-term treatments. The weight tends to return when they stop. The drug you can sustain is the drug that works.
- What am I doing alongside it? This is the lever most under your control, and the one most ignored, see below.
The "should I wait for retatrutide?" question
It is tempting. The number is dramatic. But here is the honest arithmetic:
- Retatrutide is years away from a possible approval (industry timelines point to 2027 to 2028, after the rest of the TRIUMPH trials report).
- Waiting means not treating a condition that has real cardiovascular and metabolic costs in the meantime.
- The drugs available today are highly effective. A woman who loses 18% of her body weight on tirzepatide over the next two years is in a far better place than one who waited for a drug that might deliver 25%.
For most women, the right move is not to wait. It is to use what is available well, build the foundation that carries to any future drug, and have an open conversation with a prescriber if and when retatrutide is approved. Switching between these medications is well within standard practice; the door does not close.
What does not change between the drugs
Whichever molecule you are on, three things are constant, and they matter more, not less, as the weight loss gets larger:
- Muscle is at risk. A quarter to a third of weight lost is lean mass without deliberate steps. More total loss means more absolute muscle on the line.
- Protein protects it. 1.2 to 1.6 g/kg of goal body weight: about 120 g a day for most people.
- Resistance training multiplies the effect. Two sessions a week. The single best insurance against losing the wrong kind of weight.
The drug determines how much you lose. These habits determine what you lose. (See why muscle is the number that matters and strength training that fits a tired body.)
What to do with this
Only one of these is something you can be prescribed today, and it is the one the calculator models. Put your dose in and see the ceiling it implies.
Sources
- Jastreboff AM, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity, A Phase 2 Trial. NEJM 2023;389:514-526. NEJM
- Eli Lilly and Company. TRIUMPH-1 Phase 3 topline results. 21 May 2026. Lilly investor news
- Aronne LJ, et al. Tirzepatide vs Semaglutide for Obesity (SURMOUNT-5). NEJM 2025. NEJM
- Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). NEJM 2022;387:205-216. NEJM
- Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). NEJM 2021;384:989-1002. NEJM
Medical disclaimer: Articles in the foodose research library are educational, not medical advice. Retatrutide is investigational and not available by prescription. The choice between medications is your prescriber's, made with your full history. See our full medical disclaimer.