What did the retatrutide Phase 2 trial show?

The 48-week Phase 2 trial published in the New England Journal of Medicine in 2023 enrolled 338 adults. Mean weight loss was 8.7% on 1 mg, 17.1% on 4 mg, 22.8% on 8 mg, and 24.2% on 12 mg, versus 2.1% on placebo. At 12 mg, 83% of participants lost at least 15% of body weight, and the weight curves had not yet flattened when the trial ended.

How does retatrutide compare to Wegovy and Zepbound for weight loss?

The trials were separate, not head to head, so the comparison is approximate. Semaglutide 2.4 mg produced 14.9% average weight loss at 68 weeks in STEP 1. Tirzepatide 15 mg produced 20.9% at 72 weeks in SURMOUNT-1. Retatrutide 12 mg produced 28.3% at 80 weeks in TRIUMPH-1. Semaglutide and tirzepatide are FDA approved and available now; retatrutide is not.

Does everyone lose the same amount on retatrutide?

No. The headline numbers are averages, and the spread is wide. In TRIUMPH-1 at 12 mg, 27.2% of participants lost 35% or more of their body weight, while 37.5% did not reach 25%. People with type 2 diabetes lost less: 20.8% at 12 mg in TRIUMPH-2 versus 28.3% in TRIUMPH-1. Lower doses and shorter treatment also produce smaller numbers.

Do you regain weight after stopping retatrutide?

No retatrutide withdrawal data has been published yet. The approved drugs in the same class show substantial regain. In the STEP 1 extension, people who stopped semaglutide regained about two-thirds of their lost weight within one year. In SURMOUNT-4, people switched from tirzepatide to placebo regained 14.0 percentage points over 52 weeks while those who continued kept losing. Retatrutide is likely to follow the same pattern.

How Much Weight Do People Lose on Retatrutide?

Q: How much weight do people lose on retatrutide?

In the Phase 3 TRIUMPH-1 trial of 2,339 adults with obesity or overweight and no diabetes, average weight loss at 80 weeks was 19.0% on 4 mg, 25.9% on 9 mg, and 28.3% on 12 mg, versus 2.2% on placebo. At 12 mg that averaged 70.3 lbs from a starting weight of 248.5 lbs. Retatrutide is investigational and not FDA approved.

The short answer: in the pivotal Phase 3 trial, adults without diabetes lost an average of 19.0% of body weight on 4 mg, 25.9% on 9 mg, and 28.3% on 12 mg over 80 weeks, versus 2.2% on placebo. At 12 mg that averaged 70.3 lbs from a starting weight of 248.5 lbs. Nearly half of the 12 mg group lost 30% or more. Those are trial averages for an investigational drug that the FDA has not approved, not a promise for any individual.

What did the Phase 2 trial show, dose by dose?

The first weight-loss numbers came from a 48-week Phase 2 trial published in the New England Journal of Medicine in June 2023. It enrolled 338 adults with obesity, or overweight plus a weight-related condition, and no diabetes (Jastreboff et al., NEJM, 2023).

Mean weight change at 48 weeks:

1 mg: −8.7%
4 mg: −17.1%
8 mg: −22.8%
12 mg: −24.2%
Placebo: −2.1%

At 24 weeks the 12 mg group had already lost 17.5%. At 48 weeks, 100% of the 12 mg group had lost at least 5%, 93% had lost at least 10%, and 83% had lost at least 15%. The authors noted that the weight curves were still falling when the trial ended, so 48 weeks did not capture the full effect.

What did TRIUMPH-1 show at 80 weeks?

TRIUMPH-1 is the registrational obesity trial. Lilly reported topline results on May 21, 2026. It randomized 2,339 adults with obesity, or overweight plus at least one weight-related condition, and no type 2 diabetes. Average starting weight was 248.5 lbs and average BMI was 40.0 (Eli Lilly, May 21, 2026).

Mean weight change at 80 weeks:

4 mg: −19.0% (47.2 lbs)
9 mg: −25.9% (64.4 lbs)
12 mg: −28.3% (70.3 lbs)
Placebo: −2.2% (5.5 lbs)

The threshold data is the part that shows how the average splits into people:

Lost 25% or more: 27.8% on 4 mg, 52.9% on 9 mg, 62.5% on 12 mg, 2.2% on placebo
Lost 30% or more: 15.3% on 4 mg, 37.9% on 9 mg, 45.3% on 12 mg, 0.5% on placebo
Lost 35% or more: 5.9% on 4 mg, 20.8% on 9 mg, 27.2% on 12 mg, 0.3% on placebo

A 104-week extension followed 532 participants who started with a BMI of 35 or higher. At two years, the 12 mg group averaged 30.3% (85.0 lbs), and the 9 mg group averaged 29.5%. Participants who moved from placebo to active drug in the extension lost 19.2%.

What did the other Phase 3 trials show?

Three more TRIUMPH readouts tested different populations, and the numbers move with the population.

TRIUMPH-2 (type 2 diabetes plus obesity or overweight, 1,152 participants, 80 weeks): 12.7% on 4 mg, 19.1% on 9 mg, 20.8% on 12 mg, versus 4.0% on placebo. A1C fell by up to 1.6 percentage points (Eli Lilly, July 23, 2026). Every drug in this class produces less weight loss in people with diabetes, and retatrutide follows the pattern.

TRIUMPH-3 (severe obesity with established cardiovascular disease, 1,949 participants, 80 weeks): 21.6% on 9 mg and 22.6% on 12 mg, versus 3.2% on placebo.

TRIUMPH-4 (obesity or overweight with knee osteoarthritis, 445 participants, 68 weeks): 26.4% on 9 mg and 28.7% on 12 mg, versus 2.1% on placebo. Lilly framed the top dose as up to 71.2 lbs (Eli Lilly, December 11, 2025). This was the first Phase 3 result to land, and it tracks the TRIUMPH-1 numbers closely.

Our trial tracker covers the full program and what is still pending.

How does it compare to semaglutide and tirzepatide?

The two approved comparators had their own placebo-controlled trials in adults without diabetes, so the comparison is between trials rather than head to head. Populations, durations, and analysis methods differ, so treat the gap as approximate.

Semaglutide 2.4 mg (Wegovy), STEP 1: −14.9% at 68 weeks versus −2.4% on placebo, in 1,961 adults (Wilding et al., NEJM, 2021)
Tirzepatide 15 mg (Zepbound), SURMOUNT-1: −20.9% at 72 weeks versus −3.1% on placebo, in 2,539 adults (Eli Lilly, NEJM publication, 2022)
Retatrutide 12 mg, TRIUMPH-1: −28.3% at 80 weeks versus −2.2% on placebo, in 2,339 adults

Each step added a receptor and roughly 6 to 7 percentage points of weight loss. Our explainer on retatrutide versus tirzepatide covers what the glucagon receptor adds. Tirzepatide is available now, and mounjaro.md covers it in depth. Semaglutide is covered at ozempic.md.

What does "up to 28%" mean?

Three things, and they all cut the headline number down.

It is the top dose. The 4 mg arm in TRIUMPH-1 lost 19.0%, not 28.3%. Retatrutide has no approved dose, and the trials reached 12 mg through a supervised escalation schedule. Not everyone tolerated it. Discontinuation for adverse events ran 11.3% at 12 mg versus 4.9% on placebo. Our guide to retatrutide side effects covers the details.

It is an average. In the 12 mg group, 27.2% lost 35% or more, and 37.5% did not reach 25%. In Phase 2, 17% of the 12 mg group did not reach 15% at 48 weeks. Some people respond far above the mean and some far below it, and no trial has yet published a reliable way to predict who.

It is the longest timepoint. Weight loss builds over months. In Phase 2, the 12 mg group had lost 17.5% at 24 weeks and 24.2% at 48 weeks, and the curve had not flattened. In TRIUMPH-1, the 104-week extension added about two more points on top of the 80-week result. A plateau appears to arrive somewhere between 18 months and two years at the top dose. Earlier numbers will be smaller.

What happens to the weight when you stop?

No retatrutide withdrawal data has been published. The two approved drugs in the class give the best available preview, and both point the same way.

In the STEP 1 extension, participants who stopped semaglutide 2.4 mg regained about two-thirds of their lost weight within one year (Wilding et al., Diabetes, Obesity and Metabolism, 2022). In SURMOUNT-4, 670 participants lost 20.9% on tirzepatide over 36 weeks. Those switched to placebo regained 14.0 percentage points over the next 52 weeks, while those who continued lost a further 5.5% (Aronne et al., JAMA, 2024).

The likely reading for retatrutide is that the weight-loss number is a treatment number. Stopping the drug reverses most of it unless something else holds the weight down. Energy balance still governs the long run, and calories.md covers that side of the equation.

The bottom line

Retatrutide produced the largest average weight loss ever reported for an obesity drug: 24.2% at 48 weeks in Phase 2, 28.3% at 80 weeks in TRIUMPH-1, and 30.3% at 104 weeks in the extension, all at 12 mg. Lower doses, people with diabetes, and shorter timepoints all give smaller numbers, and the range around every average is wide. None of this is prescribable. Lilly plans to file with the FDA in the first quarter of 2027, and our tracker on when retatrutide may be approved follows what happens next.

Last updated: August 2026. This article is for informational purposes only and does not constitute medical advice. Retatrutide is an investigational drug and is not approved or available by prescription.