Retatrutide Research: Phase 2 and Phase 3 Explained
What each kind of study checked
A small first study in 2022 checked how long retatrutide stayed in blood. Two mid-stage Phase 2 studies in 2023 checked weight and type 2 diabetes. A smaller Phase 2a study in 2024 checked liver fat. Lab work in 2024 checked the three hormone actions. The large, late Phase 3 TRIUMPH-1 study reported weight results in 2025.
Retatrutide has three hormone actions. The first lowers hunger and helps insulin work. The next prompts insulin after meals. The last may increase fuel use while reducing liver fat.
The sections follow one study at a time. Each number stays with its study and citation. Group findings can't promise your own result.
Published Phase 2 studies first tested retatrutide for weight and type 2 diabetes in 2023. A smaller Phase 2a study checked liver disease in 2024. The large Phase 3 TRIUMPH-1 and TRIUMPH-4 studies gave early results in 2025. Lab work in 2024 also mapped the start of each hormone action. Each citation leads to the matching report.
What Retatrutide changes in the body
Three hormone actions begin when retatrutide meets cells. The first lowers hunger and helps insulin lower blood sugar. The second also helps release insulin and manage fat. The last action may burn fuel, use liver fat, and release sugar. The first two can help hold that sugar rise down.
Tests in cells compared retatrutide with 1 natural hormone at a time. The drug started all three actions, but by different amounts. A result in cells can't predict your weight loss or safety.
A 2024 study used a very strong microscope [4]. It showed the drug attached where all three hormone messages enter cells. The images showed fit and shape, not a result in people. This microscope work is source 4 in the list.
The drug also has two changes that slow its removal. One shields the protein chain from quick breakdown. A fatty attachment helps it stay with a blood protein. The result is a half-life near 6 days [19]. Half-life means blood takes that long to lose half.
What Retatrutide's GLP-3 nickname leaves out
Some people call Retatrutide GLP-3. They mean the drug acts in three ways. Here, 3 counts the hormone actions. The nickname isn't a formal medical name. GLP-1 is a hunger and blood sugar hormone. GLP-2 mainly works in the gut. That GLP-2 hormone isn't part of retatrutide.
Researchers call retatrutide a three-hormone drug. That means three hormone actions come from one drug. The GLP-3 nickname tells you nothing about results or safety.
How Retatrutide affects hunger, sugar, and fat
The first hormone action slows the stomach and lowers hunger. It also helps insulin work when blood sugar rises. Semaglutide and tirzepatide copy GLP-1, the hunger and blood sugar hormone. You may know that action from those drugs.
The second action prompts insulin release after food. It may also change fat storage and fullness. Tirzepatide has the first two actions. Retatrutide adds a third one.
That third hormone is glucagon. It tells the liver to release sugar. The other two actions help offset the rise. The balance may increase fuel use while reducing liver fat [13].
Related hunger drugs may also change the wish for rewarding food. In rodents, researchers studied brain areas tied to reward and craving [15]. Early human work has begun. Most of that brain finding still comes from animals, not people.
What the mid-stage Phase 2 weight study found in 2023
Jastreboff's 2023 Phase 2 study enrolled 338 adults without type 2 diabetes. This was a mid-stage test in people. Each person had a BMI of at least 30. A BMI of 27 also counted with another illness. BMI compares weight with height. People got placebo or 1 mg, 4 mg, 8 mg, or 12 mg as a weekly shot beneath the skin. Placebo means a dummy shot with no retatrutide.
At 48 weeks, mean weight loss was 8.7% on 1 mg. It was 17.1% on 4 mg, 22.8% on 8 mg, and 24.2% on 12 mg. Placebo loss was 2.1%.
By 24 weeks, the 12 mg group had lost 17.5%. Placebo loss then was 1.6%. Every retatrutide group had greater loss than placebo [1].
About 26% lost at least 30% of their weight. That result came from the Phase 2 study [16]. No drug group had dangerously low blood sugar.
What the Phase 2 type 2 diabetes study found in 2023
Rosenstock's 2023 Phase 2 study enrolled 281 adults. All had type 2 diabetes. Their three-month blood sugar test ranged from 7–10.5%. Their BMI, which compares weight with height, ranged from 25–50. These were entry rules, not results. The study compared placebo, dulaglutide, and retatrutide at 4, 8, or 12 mg each week.
At 36 weeks, the three-month blood sugar result fell 2.02% with 12 mg. Placebo brought almost no change. In the 12 mg group, 82% reached 6.5% or less [2].
Mean weight loss was 16.94% with the 12 mg amount. It was 3.0% with placebo and about 3.5% with dulaglutide. Retatrutide did better on weight and blood sugar. A group result can't tell your own change.
What the 2024 liver-fat study found
Sanyal's 2024 Phase 2a study included 98 adults. Each had at least 10% liver fat. A special scan measured the share of fat in the liver. They came from the Phase 2 weight study. Each had fatty liver disease tied to poor sugar and fat health.
At 24 weeks, mean liver fat fell 42.9% on 1 mg. It fell 57.0% on 4 mg, 81.4% on 8 mg, and 82.4% on 12 mg. Placebo rose 0.3%. Every drug group did better than placebo [3].
By 48 weeks, 86% of the 12 mg group had liver fat below 5%. The same was true for 93% of the 8 mg group. Those findings led to planned Phase 3 liver studies. The Phase 2 study assigned people to groups by chance.
What Retatrutide changed in deep belly fat
Coskun's 2025 Phase 2 diabetes study used body scans at 36 weeks [6]. The scans estimated fat, muscle, and other tissue. Total fat fell 4.9% on 0.5 mg. It fell 15.2% on 4 mg, 26.1% on 8 mg, and 23.2% on 12 mg.
Placebo loss was 4.5%. Dulaglutide loss was 2.6%. Deep belly fat fell as much as 31.4% in the 8 mg group.
Researchers think the third hormone action helps break down stored belly and liver fat. Lean mass also fell. Lean mass includes muscle and other tissue besides fat. Its share of the loss wasn't worse than with other weight drugs in this Phase 2 diabetes study [6].
In mice, a strong third action lowered blood protein parts and broke down muscle. Food protein protected lean mass at lower doses [14]. Those were early animal studies. Phase 2 scans in people didn't find an unusually large loss of lean mass.
What the Phase 3 TRIUMPH studies have found
The large, late Phase 3 TRIUMPH set covers at least four studies. Together, the studies enrolled more than 5,800 people. The name is just a study label.
TRIUMPH-1 followed adults without type 2 diabetes. At the 80-week main check, the 12 mg group lost a mean 28.3%, or 70.3 lbs. Some 45.3% lost at least 30%. Another 65.3% reached a BMI below 30. The different shares show how people in one group varied.
People with a BMI of at least 35 stayed for 104 weeks. Their mean loss was 30.3%, or 85.0 lbs. The 4 mg group lost 19.0%, or 47.2 lbs [5]. Leaving rates were 4.1% on 4 mg, 6.9% on 9 mg, and 11.3% on 12 mg. Placebo had a 4.9% rate [17].
TRIUMPH-4 followed adults with obesity and knee arthritis. Its 68-week check found 28.7% mean loss on 12 mg. The group's score on a knee-pain scale fell 75.8%. Daily movement also improved [8]. Your knee may not match the group mean.
TRIUMPH-3 is still checking heart health. No public result had shown changes in heart attacks, strokes, or heart-related deaths by May 2026.
What Retatrutide results held up in Phase 2 and Phase 3
Earlier Phase 2/3 work tied larger doses to more lost weight. That includes both Phase 2 and Phase 3. Comparisons with two-hormone drugs were indirect. No one study tested both drugs together. The review covered medicines with 1 hunger-hormone action.
A 2024 review of seven drugs put 12 mg retatrutide at 22.10% weight loss. It found a 17.00 cm smaller waist. The two-action drug figures were 16.53% and 13.23 cm [9]. TRIUMPH-5 is planned as the first direct test against tirzepatide. The direct test matters because the old groups differed.
Another review combined three studies with 878 patients. Each study placed people in groups by chance. Across them, mean weight changed 14.33%. A 95% range showed how much that estimate could vary. The review still found a clear difference from placebo.
Weight compared with height, waist size, and blood pressure improved. Fasting sugar and the three-month sugar test improved too [7]. The exact size varied among the studies.
A second review combined 3 studies with 640 patients. Mean weight changed 10.66 kg. Its 95% range was wide. One blood fat also fell.
Blood pressure and the three-month sugar test improved. People on retatrutide were more likely to lose at least 20% [12]. The 95% range for that edge was very wide. The size of the edge isn't settled. Joined results can't predict your exact change.
What Retatrutide vs Tirzepatide can tell you
Tirzepatide copies two hormone messages. Retatrutide copies those two and a third. The extra action may increase fuel use while reducing liver fat.
A 2024 review compared separate studies. It found 22.10% weight loss with 12 mg retatrutide. It found 16.53% with 15 mg of the two-action drug [9].
No study had placed both drugs in one test by May 2026. TRIUMPH-5 is planned to do that. The old studies differed in people and length.
The extra action in retatrutide may help break down stored body and liver fat [13]. Much of the reason comes from lab and animal work. Those findings may help explain more loss. They can't settle which drug is better for you.
Both drugs often caused nausea, vomiting, diarrhea, and constipation as doses rose. In TRIUMPH-1 Phase 3, 11.3% left the 12 mg group [5][17]. Other Phase 3 drugs had rates in the same range.
The retatrutide vs tirzepatide answer remains limited. TRIUMPH-1 tested retatrutide alone. No finished study has put the two drugs in one fair test.
Why Retatrutide and Tirzepatide still need one test
Separate Phase 2 and Phase 3 studies hint at more mean weight loss with retatrutide. A 2024 review put 12 mg retatrutide at 22.10%. The top dual-drug dose reached 16.53% [9]. Goldney's 2025 review found the same course. It also described the planned TRIUMPH-5 direct study [16].
No published study had placed the drugs head to head by mid-2026. Retatrutide's third hormone action may burn more fuel. Side effects look much alike so far. A fair direct study is still needed.