Retatrutide vs tirzepatide: retatrutide, Lilly’s experimental triple agonist, produced about 25% weight loss at its top dose in its first peer-reviewed phase 3 trial,[1] compared with about 21% for tirzepatide (Zepbound) in its own trial.[8] But the two have not yet been compared head to head,[11] and retatrutide is not FDA-approved: Lilly plans to file in early 2027.[12]
For background, see our retatrutide profile, retatrutide dosage guide, retatrutide vs semaglutide and tirzepatide profile.
How they work
| Retatrutide | Tirzepatide | |
|---|---|---|
| Receptors | GIP, GLP-1 and glucagon[7] | GIP and GLP-1[9] |
| Half-life | About 6 days[7] | About 5 to 6 days[9] |
| Dosing | Once weekly (studied)[1] | Once weekly[9] |
| Doses | 4, 9 or 12 mg (studied)[1] | 2.5 to 15 mg[9] |
| Status | Investigational[12] | FDA-approved (Mounjaro, Zepbound)[9][10] |
The extra glucagon action is thought to increase energy use and liver fat burning, on top of the appetite effects of GIP and GLP-1.[7]
Weight loss compared
| Trial | Drug and top dose | People | Weeks | Weight change | Placebo |
|---|---|---|---|---|---|
| TRIUMPH-1 | Retatrutide 12 mg | 2,339 with obesity | 80 | −25.0% | −3.9%[1] |
| SURMOUNT-1 | Tirzepatide 15 mg | 2,539 with obesity | 72 | −20.9% | −3.1%[8] |
| TRIUMPH-2 | Retatrutide 12 mg | 1,152 with obesity and type 2 diabetes | 80 | −18.8% | −5.1%[2] |
| TRIUMPH-4 | Retatrutide 12 mg | 445 with obesity and knee arthritis | 68 | −28.7%* | −2.1%[4] |
*Company-reported, using the “efficacy estimand,” which counts only people who stayed on treatment. The peer-reviewed figures above use the stricter treatment-regimen analysis.
The head-to-head trial: TRIUMPH-5
TRIUMPH-5 is randomizing about 800 adults with obesity to retatrutide or tirzepatide and measuring weight change at 80 weeks. Its primary completion is expected in November 2026.[11] Until it reports, no one can say for certain how much stronger retatrutide is.
Weight loss by retatrutide dose
In TRIUMPH-1, weight loss climbed with dose: 17.6% on 4 mg, 23.7% on 9 mg and 25.0% on 12 mg over 80 weeks, versus 3.9% on placebo.[1] The 9 mg and 12 mg results were close, much as the 8 mg and 12 mg results were in phase 2 (22.8% and 24.2% at 48 weeks).[6]
People with type 2 diabetes lost less weight on retatrutide. In TRIUMPH-2, the three retatrutide doses lowered weight 11.9%, 16.8% and 18.8%, versus 5.1% on placebo.[2]
Other results
- Type 2 diabetes: in TRANSCEND-T2D-1, retatrutide 12 mg lowered HbA1c by 1.94 points and weight by 15.3% over 40 weeks.[5] Earlier, in phase 2, it outperformed dulaglutide on HbA1c.[18]
- Knee pain: in TRIUMPH-4, pain scores fell about 75% on retatrutide versus 40% on placebo.[4]
- Sleep apnea: tirzepatide is FDA-approved for it;[9] retatrutide reduced apnea events in a TRIUMPH-1 subgroup.[1]
- Heart: in TRIUMPH-3, which enrolled people with heart disease, retatrutide’s effect on heart events was not statistically significant either way; the trial was not designed to test it.[3] Mounjaro is approved to reduce heart attack and stroke risk in type 2 diabetes.[10]
Side effects compared
| Side effect | Retatrutide 12 mg (TRIUMPH-4) | Placebo | Zepbound 15 mg (label) | Placebo |
|---|---|---|---|---|
| Nausea | 43.2% | 10.7%[4] | 28% | 8%[9] |
| Diarrhea | 33.1% | 13.4%[4] | 23% | 8%[9] |
| Vomiting | 20.9% | 0.0%[4] | 13% | 2%[9] |
| Constipation | 25.0% | 8.7%[4] | 11% | 5%[9] |
| Dysesthesia (abnormal skin sensations) | 20.9% | 0.7%[4] | 0.4% | 0.1%[9] |
| Stopped due to side effects | 18.2% | 4.0%[4] | 6.7% | 3.4%[9] |
- Dysesthesia is the clearest difference: tingling, burning or skin sensitivity was reported in 7% to 21% of people on retatrutide across phase 3 trials, depending on dose and trial.[2][4]
- Stopping treatment in TRIUMPH-4 was strongly linked to starting weight; Lilly said some people stopped because they felt they had lost too much weight.[4]
- Low blood pressure was more common on retatrutide in TRIUMPH-2 (up to 6% vs under 1%).[2]
- Heart rate rose with dose in phase 2, peaking at 24 weeks.[6]
- Boxed warning: tirzepatide carries a thyroid C-cell tumor warning.[9] Retatrutide has no approved label yet.
Other warnings on the tirzepatide label
The Zepbound label lists several less common risks that a clinician will screen for:[9]
- Gallbladder disease: in the weight-loss trials, gallbladder inflammation (cholecystitis) was reported in 0.7% on Zepbound versus 0.2% on placebo.
- Pancreatitis: stop the drug if it is suspected.
- Low blood sugar: the risk is higher when combined with insulin or sulfonylureas.
- Birth control pills: they may work less well. The label advises switching to a non-oral method, or adding a barrier method, for 4 weeks after starting and after each dose increase.
- Surgery: tell your care team, because food aspiration under anesthesia has been reported with GLP-1 drugs.
- Pregnancy: stop Zepbound once pregnancy is recognized.
Retatrutide’s trials list similar stomach-related effects, but its rarer risks will only be clear once full phase 3 safety data are reviewed. In TRIUMPH-2, seven deaths occurred across all groups, and investigators judged none related to the study drug.[2]
Who should not take tirzepatide
The label says not to use Zepbound if you or a family member has had medullary thyroid cancer, if you have MEN 2, or if you have had a serious allergic reaction to tirzepatide.[9]
Dosing compared
| Retatrutide (trials) | Tirzepatide (Zepbound label) | |
|---|---|---|
| Start | Escalated from a low starting dose; phase 2 found a 2 mg start reduced stomach side effects[6] | 2.5 mg weekly for 4 weeks[9] |
| Increase | Stepwise to 4, 9 or 12 mg[1] | +2.5 mg every 4 weeks or more[9] |
| Maintenance | 4, 9 or 12 mg | 5, 10 or 15 mg[9] |
There is no official dose equivalence or switching protocol between the two. The Zepbound label says not to combine it with other GLP-1 drugs.[9]
If a Zepbound dose is missed, the label says to take it within 4 days; after that, skip it and take the next dose on the usual day.[9]
Availability and legal status
- Tirzepatide: FDA-approved as Mounjaro and Zepbound, available by prescription.[9][10]
- Retatrutide: not approved anywhere. Lilly plans to file with FDA in the first quarter of 2027.[12] Since August 2026, a single-patient expanded access program is open to some adults with severe obesity complications who cannot join a trial.[13]
- Compounding: FDA says retatrutide cannot be used in compounding and has warned companies selling it as a “research” product.[14]
- Gray-market use: a 2026 study of social media users taking unapproved retatrutide documented self-reported side effects.[15]
- Sports: retatrutide is not named on WADA’s 2026 list, but as an unapproved drug it falls under the S0 category, which is banned at all times. Approved tirzepatide is not prohibited.[16]
For how tirzepatide compares with semaglutide, see our semaglutide vs tirzepatide guide; that head-to-head trial found 20.2% vs 13.7% weight loss.[17]
Questions to ask a clinician
- Am I a candidate for tirzepatide, and which dose should I aim for?
- Would I qualify for a retatrutide clinical trial or the expanded access program?
- Do any of my medicines, such as insulin or birth control pills, need adjusting?
- What should I do if side effects make it hard to increase my dose?
