Retatrutide vs Tirzepatide: What the Trials Show

If you've spent any time reading about the next wave of weight-loss medicines, two names keep coming up: tirzepatide, the drug already in pharmacies as Mounjaro and Zepbound, and retatrutide, the one that keeps producing headline weight-loss figures from its trials. People naturally want to line them up side by side and ask the obvious question: which one is better?

It's a fair question, and the trial numbers are genuinely striking. But there's a big asterisk hanging over the comparison, and we'll be honest about it from the start. One of these drugs is approved and prescribed today. The other is still being tested and can't be prescribed at all. That changes everything about how you should read the percentages.

The mechanism: two hormones versus three

Both drugs belong to the same broad family — they mimic gut hormones that influence appetite, fullness and blood-sugar control. The difference is how many hormone receptors each one targets.

Tirzepatide is a dual agonist. It activates two receptors at once: GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide). Both are incretin hormones your gut releases after eating. Acting on the two together seems to dampen appetite and slow stomach emptying more than targeting GLP-1 alone, which is part of why tirzepatide has outperformed the single-target drugs in trials. If you want the fuller picture of the class, we've written about how GLP-1 medications work.

Retatrutide is a triple agonist. It hits the same two receptors — GLP-1 and GIP — and adds a third: the glucagon receptor. That third target is the interesting part, and it's worth pausing on, because glucagon usually has a reputation for raising blood sugar.

Why add glucagon-receptor activity?

It sounds counter-intuitive to deliberately switch on glucagon when you're treating obesity. The thinking is that glucagon does more than nudge blood sugar — it can increase energy expenditure and influence how the liver handles fat. The hope is that, combined with the appetite-suppressing GLP-1 and GIP effects, the extra glucagon activity helps the body burn slightly more energy on top of eating less. The GLP-1 component is partly there to keep blood sugar in check so the glucagon effect doesn't cause problems.

That's the theory. Whether the third receptor is truly what drives retatrutide's results, or whether it's simply a very potent molecule overall, isn't something a single comparison can settle. We've gone deeper into the drug itself in retatrutide explained.

What the trials actually showed

Here's where the numbers get attention-grabbing. Let's take them one trial at a time, because reading them as a clean head-to-head is exactly the mistake to avoid.

Tirzepatide — SURMOUNT-1

The pivotal obesity trial for tirzepatide, SURMOUNT-1, was published in the New England Journal of Medicine in 2022. It enrolled adults with obesity, or overweight with a weight-related condition, but without type 2 diabetes, and ran for 72 weeks. According to Eli Lilly's announcement of the results, average weight reductions were:

• 16.0% on the 5 mg dose (about 16 kg / 35 lb)
• 21.4% on the 10 mg dose (about 22 kg / 49 lb)
• 22.5% on the 15 mg dose (about 24 kg / 52 lb)

Placebo, for context, came in around 2.4%. Those are large, sustained reductions — and crucially, they come from a drug you can actually be prescribed.

Retatrutide — the Phase 2 trial

Retatrutide's most-discussed obesity data started with the Phase 2 trial led by Ania Jastreboff and colleagues, published in the New England Journal of Medicine in 2023. It enrolled 338 adults with obesity or overweight (without type 2 diabetes) and tested doses of 1 mg, 4 mg, 8 mg and 12 mg over 48 weeks. Lilly reported a mean weight reduction of up to 17.5% at 24 weeks, rising to up to 24.2% on the 12 mg dose by 48 weeks. The 8 mg group reached roughly 22.8%.

Retatrutide — the Phase 3 readout

More recently, the first Phase 3 results from Lilly's TRIUMPH-1 trial reported even larger figures — a mean weight loss of around 28.3% on the 12 mg dose at 80 weeks in adults with obesity but without diabetes, with a meaningful share of participants losing 30% or more of their body weight. Impressive as that is, it's still trial data on a drug that hasn't been approved.

The asterisk: these are not a head-to-head

This is the part that gets glossed over in most "drug A beat drug B" write-ups. SURMOUNT-1 and the retatrutide trials are separate studies. They differ in ways that make a direct percentage comparison unreliable:

• Different durations — 72 weeks for SURMOUNT-1, 48 weeks for retatrutide's Phase 2, 80 weeks for TRIUMPH-1. Weight loss curves keep moving over time, so trial length matters.
• Different doses and titration schedules.
• Different participant groups — varying starting weights, BMIs and baseline characteristics.
• No one randomised the same people to both drugs. Nobody has run a trial putting retatrutide directly against tirzepatide in the same room, on the same protocol.

Until that head-to-head trial exists, saying "retatrutide produces more weight loss than tirzepatide" is an inference, not a proven fact. The numbers point in that direction, and many clinicians expect retatrutide to land higher — but expectation isn't the same as evidence.

The difference that matters most: approval status

If you take one thing from this article, make it this. The gap between these two drugs isn't really about percentages. It's about availability.

Tirzepatide is approved. In the UK, the MHRA authorised Mounjaro for weight management in November 2023; the US FDA approved it as Zepbound for chronic weight management on the same day. It's prescribed, monitored and backed by a growing real-world safety record. If you're starting it or already on it, our Mounjaro week-by-week guide walks through what the early weeks tend to look like.

Retatrutide is investigational. It has not been approved by the MHRA, the FDA, the EMA or any other regulator. In Lilly's own words, it is a molecule legally available only to participants in the company's clinical trials. Phase 3 results are still being reported, and even on an optimistic timeline a regulatory decision is some way off. You cannot get a legitimate prescription for it today, full stop.

A serious warning about "buying retatrutide" online

Because the trial numbers are so eye-catching, a grey market has sprung up selling vials labelled "retatrutide" — often as "research chemicals" or "not for human use". Please don't go near it. Here's why:

• There's no approved product to copy. Anything sold as retatrutide is unlicensed and made outside any regulated supply chain.
• You don't know what's in the vial. No regulator has verified the contents, dose, purity or sterility. It could be the wrong substance, the wrong strength, or contaminated.
• No clinical oversight. Trial participants are screened, titrated slowly and monitored by clinicians. A vial bought online comes with none of that.
• The safety record simply isn't complete yet. We don't have the years of real-world data that established drugs have.

If you want a medication for weight loss now, the sensible route is a conversation with a doctor about an approved option, not an unverified product from the internet. The potential side effects of these drugs are real and worth understanding — we've covered the retatrutide picture in retatrutide side effects.

So which one is better?

Honestly? It's too early to crown a winner, and anyone who tells you otherwise is getting ahead of the evidence.

On the trial numbers alone, retatrutide's results look larger — but they come from different studies, and the highest figures come from a drug that doesn't yet exist as a product you can use. Tirzepatide's advantage is that it's real and available now, with a known dosing schedule, regulatory approval and a growing safety record. For anyone making a decision today, that's not a small thing — it's the whole thing.

The fairer framing is this: tirzepatide is a powerful, approved medicine that's helping people right now. Retatrutide is a promising candidate that might raise the ceiling further if the Phase 3 data hold up and regulators approve it. Both stories are worth following. Neither needs hype to be interesting.

Frequently asked questions

Is retatrutide approved in the UK?

No. Retatrutide is investigational and has not been approved by the MHRA, the FDA, the EMA or any other regulator. It's available only through Lilly's clinical trials. Tirzepatide (Mounjaro) is the approved option in the UK.

Does retatrutide cause more weight loss than tirzepatide?

The trial figures for retatrutide are larger, but they come from separate studies with different durations, doses and participants — not a direct head-to-head against tirzepatide. So while the numbers point that way, it hasn't been proven in a like-for-like comparison.

What's the actual difference between the two drugs?

Tirzepatide targets two hormone receptors (GLP-1 and GIP). Retatrutide targets three — GLP-1, GIP and glucagon. The added glucagon-receptor activity is thought to increase energy expenditure on top of suppressing appetite, which may help explain retatrutide's larger trial results.

Can I buy retatrutide online to try it?

You shouldn't. Any product sold as "retatrutide" is unapproved and made outside a regulated supply chain, so its contents, purity and safety are unverified. There's no legitimate prescription source. If you want medication, speak to a doctor about an approved drug instead.

When might retatrutide be approved?

Phase 3 results are still being reported, and a regulatory decision depends on the full data package and review timelines. There's no confirmed approval date, so treat any specific "launch date" you see online with caution.

Where WeightLytic fits in

WeightLytic is a weight-loss companion app built around AI food tracking, weight-trend forecasting and GLP-1 medication tracking — whichever approved medicine you and your clinician choose. We're pre-launch right now, so there are no download links yet and no outcome promises we can't stand behind. What we can say is that the app is designed to help you see your own trend clearly rather than chase someone else's trial percentage. If that's useful to you, join the waitlist and we'll let you know when it's ready. You can also see what we're building on the features page.

This article is general information, not medical advice. Medication decisions — including anything involving tirzepatide or any investigational drug — should be made with a qualified clinician who knows your history.

Sources & references

• Jastreboff et al., Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial, New England Journal of Medicine (2023)
• Eli Lilly — Phase 2 retatrutide results (up to 24.2% at 48 weeks; investigational molecule)
• Eli Lilly — Phase 3 TRIUMPH-1 retatrutide topline results
• Jastreboff et al., Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1), New England Journal of Medicine (2022)
• Eli Lilly — SURMOUNT-1 results (16.0%–22.5% weight loss)
• European Pharmaceutical Review — MHRA authorises Mounjaro (tirzepatide) for weight management (2023)