The short answer: tirzepatide hits two hormone receptors, GIP and GLP-1. Retatrutide hits those two plus a third, glucagon. In their own trials, retatrutide's top dose produced more weight loss than tirzepatide's top dose did in its trials, with more stomach side effects and more people quitting.
But the two have never been tested against each other. The one head-to-head trial, TRIUMPH-5, hasn't reported. So every "reta beats tirz by X%" you've seen compares different trials, in different people, run for different lengths of time.
Status as of October 30, 2026: Tirzepatide is FDA-approved as Mounjaro (type 2 diabetes) and Zepbound (weight management and sleep apnea). Retatrutide is not approved anywhere. Lilly plans to file for U.S. approval in Q1 2027. Every number below comes from Lilly's trials or Lilly's label. Nothing here is medical advice or a dosing guide.
Want the short version of what's actually approved, legal and tested? Get the free BHN cheat sheet.
Retatrutide vs tirzepatide: what's the difference?
One receptor. Tirzepatide's label calls it "a GIP receptor and GLP-1 receptor agonist" (Zepbound label, Aug 2026). Retatrutide is "an agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and glucagon receptors" (NEJM, 2023). Both are Eli Lilly drugs, both are once-weekly injections.
Tirzepatide's label calls GLP-1 "a physiological regulator of appetite and caloric intake" and says "nonclinical studies suggest the addition of GIP may further contribute to the regulation of food intake." Glucagon is the new piece. The phase 2 paper's authors wrote that adding it "may augment effects on energy intake, substrate utilization, and energy expenditure." Note the verb: "we speculate." Nobody has shown in people how much of retatrutide's effect comes from glucagon.
One detail most comparison pages skip: retatrutide isn't a stronger GLP-1 drug. Compared with the body's own hormones, it's weaker at the glucagon and GLP-1 receptors (0.3 and 0.4 times as potent) and much stronger at the GIP receptor (8.9 times) (NEJM, 2023).
Reta vs tirz, side by side
Tirzepatide (Mounjaro, Zepbound) | Retatrutide | |
|---|---|---|
Receptors | GIP + GLP-1 | GIP + GLP-1 + glucagon |
FDA status | Approved: Mounjaro May 2022, Zepbound Nov 2023 | Not approved. Lilly plans to file Q1 2027 |
Half-life | About 5 to 6 days (label) | About 6 days (phase 2 paper) |
Main weight trial | SURMOUNT-1: 2,539 adults without diabetes, 72 weeks | TRIUMPH-1: 2,339 adults without diabetes, 80 weeks |
Average weight change, top dose, everyone randomized | -20.9% (15 mg) vs -3.1% placebo | -25.0% (12 mg) vs -3.9% placebo |
Stopped for side effects, top dose | 6.7% vs 3.4% placebo | 11.3% vs 4.9% placebo |
Skin sensation side effect (dysesthesia) | 0.4% vs 0.1% placebo | 12.5% vs 0.9% placebo |
Tested against each other | No result yet | No result yet |
Sources: Zepbound label, Aug 2026, TRIUMPH-1, NEJM, Sept 29, 2026, Lilly, June 6, 2026, FDA, Nov 8, 2023. The tirzepatide side-effect figures pool SURMOUNT-1 and SURMOUNT-2. Different trials, different years, so read every row as context, not a head-to-head.
Has retatrutide been tested head to head against tirzepatide?
Not with results. On October 30 I pulled every retatrutide study on ClinicalTrials.gov and kept the 32 sponsored by Eli Lilly. Two include tirzepatide:
TRIUMPH-5 (NCT06662383). The real head-to-head: a phase 3, randomized, double-blind trial of retatrutide vs tirzepatide in about 800 adults with obesity. The main result is percent weight change at 80 weeks. Status: active, not recruiting. Primary completion is estimated for November 2026. No results posted (ClinicalTrials.gov).
A liver disease master protocol (NCT07165028). About 4,500 adults with fatty liver disease. Tirzepatide and retatrutide each get their own placebo comparison, and the main outcome is serious liver events over about 224 weeks. It isn't built to compare the two for weight, and it runs to 2030 (ClinicalTrials.gov).
The only head-to-head retatrutide result so far is against Ozempic, not tirzepatide. That October 28 trial is covered in is reta safe?
Is retatrutide stronger than tirzepatide?
In separate trials, yes, it produced more weight loss. Matched as closely as the published numbers allow, the gap at the top doses is about 4 percentage points. How big it really is, nobody knows until TRIUMPH-5.
The fairest pairs use each drug's main obesity trial and its diabetes trial, with the same counting method: everyone who was randomized, whether or not they stayed on the drug.
Trial | Who | Length | Top dose | Weight change | Placebo |
|---|---|---|---|---|---|
SURMOUNT-1 (tirzepatide) | 2,539 adults, obesity or overweight, no diabetes | 72 weeks | 15 mg | -20.9% | -3.1% |
TRIUMPH-1 (retatrutide) | 2,339 adults, obesity, no diabetes | 80 weeks | 12 mg | -25.0% | -3.9% |
SURMOUNT-2 (tirzepatide) | 938 adults, overweight or obesity with type 2 diabetes | 72 weeks | 15 mg | -14.7% | -3.2% |
TRIUMPH-2 (retatrutide) | 1,152 adults, overweight or obesity with type 2 diabetes | 80 weeks | 12 mg | -18.8% | -5.1% |
Taking placebo out, that's -17.8 points for tirzepatide vs -21.0 for retatrutide in the no-diabetes trials, and -11.6 vs -13.8 in the diabetes trials. Three reasons not to treat that gap as settled:
The retatrutide trials ran 8 weeks longer. 80 weeks vs 72.
They're different trials. SURMOUNT-1 started in December 2019 and ran through COVID. TRIUMPH-1 started in July 2023, in different people at different sites (ClinicalTrials.gov; ClinicalTrials.gov).
The big numbers you see online use a different count. Lilly's headline for TRIUMPH-1 at 12 mg is -28.3%, which counts people only while they stayed on the drug (Lilly, June 6, 2026). The phase 2 trial's -24.2% at 48 weeks, in 338 people, used that same on-treatment method (NEJM, 2023). Put either next to tirzepatide's -20.9% label figure and you're comparing two different kinds of number.
So "stronger" holds up as a direction across two pairs of trials. Pairing TRIUMPH-4's -28.7% (on-treatment, 68 weeks, people with knee arthritis) with tirzepatide's -20.9% to claim an 8-point win doesn't hold up at all (Lilly, Dec 11, 2025).
Reta vs tirz side effects
Same family of side effects, more of them on retatrutide at the top doses tested. Here's TRIUMPH-1 at 12 mg next to tirzepatide's label at 15 mg, each against its own placebo.
Side effect | Retatrutide 12 mg (TRIUMPH-1) | Tirzepatide 15 mg (label pool) |
|---|---|---|
Nausea | 42.4% vs 14.8% | 28% vs 8% |
Diarrhea | 32.0% vs 13.5% | 23% vs 8% |
Vomiting | 25.3% vs 4.8% | 13% vs 2% |
Constipation | 26.1% vs 10.9% | 11% vs 5% |
Dysesthesia (skin sensation) | 12.5% vs 0.9% | 0.4% vs 0.1% |
Stopped because of side effects | 11.3% vs 4.9% | 6.7% vs 3.4% |
Sources: Lilly, June 6, 2026, Zepbound label. The tirzepatide pool covers 72 weeks and includes people with diabetes. TRIUMPH-1 ran 80 weeks in people without it.
Three more differences worth knowing:
Heart rate. Tirzepatide's label reports an average rise of 1 to 3 beats per minute (Zepbound label). Retatrutide's phase 2 trial reported "dose-dependent increases in heart rate" that "peaked at 24 weeks and declined thereafter" (NEJM, 2023). I haven't found a phase 3 heart-rate number for retatrutide in anything Lilly has published so far.
Blood pressure. Low blood pressure showed up in 1.6% on tirzepatide vs 0.1% on placebo in the label pool. In TRIUMPH-2, it was 6% on retatrutide 12 mg vs under 1% on placebo (Lancet, 2026).
The skin thing. Dysesthesia, an odd tingling or sensitive-skin feeling, is the side effect that most clearly separates the two. Up to 20.9% in one retatrutide trial, TRIUMPH-4 (Lilly, Dec 11, 2025). Under half a percent on tirzepatide.
For what it's worth, BHN's October reader survey points the same way. It's 38 self-selected readers, not a study. Of the 26 who named retatrutide as their main compound, 16 reported appetite loss, 10 a higher heart rate and 5 skin sensations.
Every retatrutide side effect from every trial is in is reta safe?
Is retatrutide FDA approved like tirzepatide?
No. Tirzepatide was approved as Mounjaro for type 2 diabetes on May 13, 2022 (FDA via BioSpace) and as Zepbound for chronic weight management on November 8, 2023 (FDA). Zepbound's label now also covers moderate to severe obstructive sleep apnea in adults with obesity.
Retatrutide isn't approved by any regulator. Lilly's latest stated plan: "Lilly plans to submit a Biologics License Application (BLA) in Q1 2027 to the U.S. Food and Drug Administration" (Lilly, Sept 29, 2026). Lilly's October 29 quarterly results didn't change that timing (Lilly Q3 2026, SEC filing). Filing isn't approval. FDA review comes after.
Reta vs tirz cost: can you even compare them?
Not really. Zepbound is a prescription drug with self-pay prices Lilly publishes. Retatrutide has no price, because Lilly can't sell a drug that isn't approved. What the closest approved drugs cost, and where online retatrutide numbers come from, is in how much does retatrutide cost.
Legality splits the same way. Tirzepatide can be prescribed. FDA says "Retatrutide and cagrilintide cannot be used in compounding under federal law" (FDA, updated Oct 1, 2026). The two legal routes to retatrutide right now, Lilly's trials and its expanded access program, are in can you legally get retatrutide.
Retatrutide or tirzepatide: which is better?
It depends what "better" means, and only one of these is a choice a pharmacy can fill.
On weight in the trials: retatrutide's numbers are higher, in separate trials.
On side effects: tirzepatide's are lower, with far less skin sensation and fewer people quitting.
On what's known: tirzepatide has an FDA label, approved doses and a list of warnings the FDA has signed off on. Retatrutide has phase 3 trial results and no label.
On what's in the pen or vial: Zepbound or Mounjaro from a pharmacy is the approved product. Every retatrutide number above comes from Lilly's own drug. None of it tells you what's in a vial from anywhere else, which is why what a lab found in thousands of vials matters here.
If you're already on tirzepatide and thinking of moving, that's its own question with its own gaps: switching from tirzepatide to retatrutide.
When will we know which is stronger?
When TRIUMPH-5 reports. Primary completion is estimated for November 2026 (ClinicalTrials.gov). Lilly has announced topline results for its other reported phase 3 retatrutide trials by press release. If it does the same here, I'll update this post with the first real head-to-head numbers.
The short version
Tirzepatide: GIP + GLP-1. Retatrutide: GIP + GLP-1 + glucagon.
Top doses, separate trials, everyone counted: -20.9% at 72 weeks for tirzepatide, -25.0% at 80 weeks for retatrutide.
More nausea, vomiting, skin sensation and quitting on retatrutide.
Tirzepatide is approved. Retatrutide isn't; Lilly plans to file in Q1 2027.
The head-to-head, TRIUMPH-5, hasn't reported. Until it does, any exact gap is a guess.
If you've been on both, reply and tell me how they compared for you: appetite, side effects, what made you choose. When TRIUMPH-5 lands, I'll put the trial numbers next to what readers actually reported.