Retatrutide vs tirzepatide vs semaglutide: how to think about the triple agonist

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):

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:

1. 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.
2. What can I tolerate? The drug you can stay on beats the drug you quit because the nausea was unmanageable. Tolerance is individual.
3. 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.
4. 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 2027–2028, 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. 1.2–1.6 g/kg of goal body weight: about 120 g a day for most women.
• 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 Steady does with this

Steady supports the medications you can actually be prescribed today, Ozempic, Wegovy, Mounjaro, Zepbound, and four more, each with its own titration schedule built in. It does not track retatrutide, because retatrutide is not yet a drug anyone can take.

What Steady does is make the comparison concrete for your body: it logs your dose, your symptoms, and your weekly weight trend, so if you and your prescriber ever discuss switching, between tirzepatide and semaglutide now, or to something new later, you are looking at thirty days of your own patterned data, not a memory. The decision becomes a comparison, not a guess.

Read next: retatrutide, explained and what 30% weight loss means for women. On choosing between today's options, see Mounjaro vs Wegovy, pausing your titration, and what happens when you stop. Overview: the retatrutide page.

Sources

1. Jastreboff AM, et al. Triple–Hormone-Receptor Agonist Retatrutide for Obesity, A Phase 2 Trial. NEJM 2023;389:514-526. NEJM
2. Eli Lilly and Company. TRIUMPH-1 Phase 3 topline results. 21 May 2026. Lilly investor news
3. Aronne LJ, et al. Tirzepatide vs Semaglutide for Obesity (SURMOUNT-5). NEJM 2025. NEJM
4. Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). NEJM 2022;387:205-216. NEJM
5. 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 Steady research hub 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.