Why Retatrutide Has Two Weight Loss Numbers: The Short Answer

Retatrutide has two weight loss numbers because its main obesity trial, TRIUMPH-1, analyzed the same data in two ways. On the 12 mg dose, adults with obesity lost an average of 28.3% of their body weight over 80 weeks under one method and 25.0% under the other. Both figures describe the same participants; each method answers a different question:

• 28.3% (efficacy estimand) estimates the weight loss if every participant had stayed on the assigned treatment for 80 weeks as intended and nobody had started another weight-loss treatment.
• 25.0% (treatment-regimen estimand) is the average for everyone who was randomized, whether or not they stopped treatment or started another weight-loss treatment. The trial's authors describe it as consistent with an intention-to-treat analysis.

The paper published in the New England Journal of Medicine in September 2026 reports 25.0% in its abstract and main results, while the company's announcements lead with 28.3%. In kilograms, from an average starting weight of 112.7 kg, the company reports 31.9 kg on the first measure and 28.2 kg on the second. Neither number is wrong, but each can only be compared with numbers measured the same way.

Efficacy Estimand vs Treatment-Regimen Estimand

An estimand is a precise definition of what a trial result is meant to estimate. The key choice is how to handle "intercurrent events": things that happen after randomization and change what a participant's final weight means, such as stopping the study drug or starting a different weight-loss treatment that the protocol does not allow. For weight end points, the TRIUMPH-1 paper calls the two approaches it used the hypothetical strategy and the treatment policy strategy. These terms come from the international ICH E9(R1) guideline on estimands, which the 2023 Phase 2 paper cites by name.

The names differ between companies. Lilly uses "efficacy" and "treatment-regimen"; the semaglutide trial STEP 1, run by Novo Nordisk, uses "trial product" and "treatment policy" for the same two ideas. Both trials define the second one as an intention-to-treat approach.

Why the Gap Is 3.3 Points in TRIUMPH-1

The two estimands only differ for participants whose trial did not go as planned. If everyone had stayed on treatment and nobody had started another weight-loss drug, both methods would give almost the same answer. The TRIUMPH-1 paper reports how often that did not happen:

• Completing the trial: 87.7% to 89.7% of participants in the retatrutide groups completed the trial, against 72.4% in the placebo group.
• Staying on the assigned treatment: 75.3% to 87.0% of the retatrutide groups adhered to their assignment, against 63.9% on placebo.
• Stopping because of adverse events: 11.2% of participants on 12 mg, against 4.6% on placebo (the paper's Table 3; its text gives 11.1%). A further 5.3% on 12 mg stopped because they or the investigator considered their weight loss excessive or sufficient.

The placebo group moves in the opposite direction. On placebo, weight loss was 2.2% under the efficacy estimand but 3.9% under the treatment-regimen estimand. One reason is that the second one also counts weight lost by placebo participants who started other obesity treatments. The investigators noted that the lack of an active comparator may have contributed to greater dropout in the placebo group, as reflected by the use of now more widely available obesity medications in that group.

Because the retatrutide figure falls and the placebo figure rises under the treatment-regimen estimand, the difference from placebo narrows more than either number on its own: 21.0 percentage points under the treatment-regimen estimand, against about 26.1 points under the efficacy estimand (our calculation from the reported means). Dose reductions, which occurred permanently in 22.5% of participants on 12 mg, are not what separates the two: the efficacy estimand explicitly allows them, and the treatment-regimen estimand counts everyone regardless of adherence.

TRIUMPH-1 Results Under Both Estimands

The same pattern runs through the other TRIUMPH-1 results. The efficacy figures below come from the company's May 2026 announcement, the treatment-regimen figures from the published paper.

The threshold figures show the gap most clearly. For the same group of participants on 12 mg, the share who lost at least 30% of their weight is 45.3% under one estimand and 36.9% under the other. The 104-week figures are almost identical, which is consistent with how the extension was set up: it enrolled a selected group of 532 participants with a BMI of 35 or more who had completed the 80 weeks on their assigned dose. How weight loss built up over time is covered in the retatrutide weight loss timeline.

Both Estimands Across the Retatrutide Trials

The company's announcements do not always report both numbers. In the three trials where both are reported, the efficacy figure is the higher one for 12 mg.

The gap varies from 1.5 points in TRANSCEND-T2D-1 to 5.0 points in TRIUMPH-4 (our calculation). TRIUMPH-4 also had the highest rate of stopping treatment because of adverse events of the five trials, 18.2% on 12 mg, which the company said was highly correlated with baseline BMI and included people who stopped because of perceived excessive weight loss. TRANSCEND-T2D-1, with the smallest gap, was the shortest trial, at 40 weeks, and had the lowest rate of stopping because of adverse events, 5.1% on 12 mg. The type 2 diabetes results are covered in retatrutide for diabetes.

The 48-week Phase 2 trial, published in 2023, reported its main results under the efficacy estimand: 24.2% on 12 mg, against 2.1% on placebo. It also used a second, "hybrid" estimand, but those results appear only in its supplementary appendix.

A Common Mistake: Comparing Different Estimands

A comparison often seen online sets 28.3% for retatrutide and 22.5% for tirzepatide against 14.9% for semaglutide. The first two are efficacy figures; the third is semaglutide's intention-to-treat figure from STEP 1. Set side by side, they suggest about 90% more weight loss with retatrutide than with semaglutide. Measured the same way, the difference is about 67% to 68% (our calculation).

On the same basis, retatrutide's figure is 1.26 times tirzepatide's and 1.67 times semaglutide's as intended, and 1.20 and 1.68 times counting everyone (our calculations). These are comparisons across separate trials, not head-to-head results. The trials lasted 68 to 80 weeks and enrolled different populations. TRIUMPH-1 participants also started at a higher average BMI: 40, against 38 in SURMOUNT-1 and 37.9 in STEP 1, according to the two drugs' labels. The full comparison is in retatrutide vs tirzepatide vs semaglutide.

Which Number Appears on a Drug Label?

For the two approved drugs, the clinical studies section of the US prescribing information reports intention-to-treat results for these trials. Tirzepatide's label gives 20.9% for 15 mg at 72 weeks in the trial it calls Study 1 (SURMOUNT-1), against 3.1% on placebo, and semaglutide's label gives 14.9% at 68 weeks in its Study 2 (STEP 1), against 2.4%. Retatrutide has no label, because it has not been approved; its status is tracked in retatrutide approval status.

How to Read Any Retatrutide Weight Loss Figure

Five details decide what a weight loss number means:

1. Estimand. Efficacy (as intended) or treatment-regimen (everyone randomized). Without it, a number cannot be compared.
2. Dose. "Up to 28.3%" is the 12 mg result; 4 mg gave 19.0% on the same measure.
3. Trial and population. In separate trials, people with type 2 diabetes lost less: 20.8% in TRIUMPH-2 against 28.3% in TRIUMPH-1, both efficacy figures at 12 mg over 80 weeks.
4. Duration. The retatrutide trials ran for 40 to 80 weeks, and the TRIUMPH-1 extension to 104 weeks.
5. Raw or placebo-adjusted. 25.0% is the average change in the 12 mg group; 21.0 points is its difference from placebo.

These figures describe trial participants under medical supervision. What is known about weight after stopping treatment is covered in weight regain after stopping retatrutide.

Sources

• Jastreboff AM, Kaplan LM, Davies MJ, et al. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. N Engl J Med. Published September 29, 2026. DOI: 10.1056/NEJMoa2604169. (TRIUMPH-1)
• Jastreboff AM, Kaplan LM, Frías JP, et al. Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med. 2023;389(6):514–526. DOI: 10.1056/NEJMoa2301972.
• Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384:989–1002. DOI: 10.1056/NEJMoa2032183. (STEP 1)
• Eli Lilly. Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial. May 21, 2026.
• Eli Lilly. Lilly's triple agonist, retatrutide, delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful Phase 3 trial. December 11, 2025.
• Eli Lilly. Lilly's triple agonist, retatrutide, demonstrated significant reductions in A1C and weight in first Phase 3 trial for treatment of type 2 diabetes. March 19, 2026.
• Eli Lilly. Lilly's triple agonist, retatrutide, successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1C. July 23, 2026.
• Eli Lilly. Lilly's triple agonist, retatrutide, delivered substantial weight loss and A1C reduction, underscoring its potential promise for people with obesity and type 2 diabetes. September 29, 2026.
• Eli Lilly. Lilly's SURMOUNT-1 results published in The New England Journal of Medicine show tirzepatide achieved between 16.0% and 22.5% weight loss in adults with obesity or overweight. June 4, 2022.
• Eli Lilly. What to know about retatrutide. Last updated September 2026.
• Eli Lilly. US prescribing information for tirzepatide for weight reduction, section 14.1. Revised August 2026.
• Novo Nordisk. US prescribing information for semaglutide injection and tablets for weight reduction, section 14.2. Revised June 2026.

Medical Disclaimer: This article is for informational purposes only and is not medical advice. Retatrutide is investigational and is not approved by the FDA for any use. It is not available by prescription, and Lilly says anything sold to consumers under its name outside its clinical trials is illegal. The figures described here are those reported in clinical trials under medical supervision.