People, tests and open questions
How Did Retatrutide Fare in Early and Larger Phase 3 Studies?
People lost weight in early tests; larger studies check lasting benefit and harm.
What is known before you read the study details?
People's weight fell and blood tests improved in early studies; lasting heart and kidney benefits remain unknown. Retatrutide still lacks approval in every country, while testing of the drug continues.
Eli Lilly developed retatrutide, and its larger Phase 3 studies called TRIUMPH continued in mid-2026. The earlier tests measured weight, blood sugar, liver fat, pressure readings and fats in blood.
Heart and kidney studies ask whether improved readings lead to fewer serious health problems. A lower test reading can't by itself tell you whether the drug protects your health.
The numbered links lead to the published papers that supplied the findings reported here. Those papers describe what changed during testing, rather than proving that lasting illness was prevented.
Early study staff also checked possible harm while testing different amounts of the drug. Their findings don't give you safe directions for using retatrutide away from study care.
The Retatrutide effects page describes sickness, hunger changes and a rise in resting pulse. Muscle loss and the weight that may return after stopping also need longer testing.
What happened in the first small safety study?
The first small study included 72 adults with type 2 diabetes and checked possible harm. Staff also followed weight and blood sugar while testing different amounts of retatrutide.
Over 12 weeks, the highest-amount group lost an extra 8.96 kilograms compared with placebo [4]. Placebo is a shot without the test drug, used to compare changes between groups.
The extra loss of 8.96 kilograms over 12 weeks wasn't the group's total weight loss. Daily blood sugar also fell in people given 3 milligrams during this early testing [4].
New health problems affected 63%, mostly involving the stomach and bowels; severe low sugar wasn't reported [4]. Researchers moved on to larger Phase 2 studies, the middle testing stage, to learn more.
After 6 days, roughly half the retatrutide was still present in blood, helping explain the weekly study shots [4]. A fatty part attached to retatrutide binds to a blood protein and slows the drug's removal.
Why did Phase 2 researchers report -24.2% weight change?
Jastreboff and colleagues reported their Phase 2 study of 338 adults in 2023. Those taking part had obesity, or they were overweight with a health problem linked to weight.
After 48 weeks, those receiving 12 milligrams lost an average of 24.2% of their weight [1]. Placebo contained no retatrutide; people receiving those shots lost 2.1% on average.
Average losses were 22.8% with 8 milligrams and 17.3% with 4 milligrams [1]. People receiving 1 milligram lost 8.7%, with study staff raising amounts in steps.
The 1, 4, 8 and 12 milligram amounts were given weekly into the fat beneath people's skin. Higher amounts brought greater weight loss but also more stomach and bowel problems.
Waists became nearly 20 centimeters smaller at the highest amount tested [10]. A 2025 Biomolecules review described the 24.2% loss as a large advance over earlier drug findings [6].
That review compared the loss with weight-loss surgery, without promising the same change for you. A Cell review discussed losses of 20-30% with drugs acting on three hormone responses [11].
Gut trouble was mostly mild or moderate; some people nevertheless left the study. About 45% felt sick at 12 milligrams, and 18% stopped at that amount [1].
The highest amount raised resting pulse by about 5-7 beats per minute, peaking at 24 weeks [1]. Bigger pulse changes at larger amounts leave questions about lasting effects on the heart.
Reviewers writing in 2026 found 63% lost at least 20% of their starting weight [12]. The review also reported a lower top blood pressure reading during testing.
How did Phase 2 testing change type 2 diabetes readings?
Rosenstock and colleagues reported on 281 adults with type 2 diabetes in the Lancet in 2023. Their Phase 2 study compared weekly amounts of 0.5-12 milligrams with placebo and another medicine.
At 24 weeks, longer-term blood sugar readings fell clearly in the 12 milligram group [2]. With placebo, a shot lacking retatrutide, the sugar reading barely changed.
The test reflects blood sugar over roughly three months, rather than one day's reading. The larger fall meant better sugar control while people were taking part in the study.
After 36 weeks, people lost 16.94% of their weight, compared with 3.00% with placebo [2]. Mild or moderate gut problems affected 35%; no deaths or severe low sugar were reported [2].
Larger amounts were linked with better blood fats and tests showing insulin worked better [13]. Pearson and colleagues studied those changes in a 2025 analysis published in 2026.
In people without diabetes, weight loss was linked with blood tests showing changes in fat burning. Researchers calculated that link; the tests didn't measure a share of body fat burned away.
Another 2025 study found less of proteins that slow the clearing of fat from blood [15]. Those changes appeared with 8 and 12 milligrams in people with type 2 diabetes.
People with obesity had those protein changes at all amounts, alongside lower fats and harmful cholesterol. Glucagon, a hormone that makes the body burn calories, may help explain the clearing of these fats.
How much liver fat changed during Phase 2 testing?
The liver study involved 98 people with fatty liver disease who were overweight or had obesity. Before treatment, their liver fat measured at least 10%, above the normal level.
Liver scans at 24 weeks showed fat fell by 82.4% with 12 milligrams and 81.4% with 8 milligrams [5]. Falls were 57.0% with 4 milligrams and 42.9% with 1 milligram; placebo brought a 0.3% rise.
At 12 milligrams, 86% had liver fat in the normal range, below 5%, after 24 weeks [5]. That means the scans returned to the study's normal range, rather than establishing a cure for you.
The fall continued through 48 weeks, reaching 86.0% with 12 milligrams [5]. Sanyal and colleagues reported these findings in Nature Medicine in 2024.
Researchers think retatrutide's glucagon response helped use the fat stored within the liver during treatment. Weight also fell, so this Phase 2 study cannot treat liver changes as entirely separate from weight loss.
A 2024 review discussed related drugs being tested for several linked health problems [9]. Those included fatty liver disease, type 2 diabetes, heart risks and repeated breathing pauses during sleep.
What can lab pictures explain about the drug?
Detailed lab pictures showed retatrutide attached at three sites where cells receive hormone messages [3]. Li and colleagues published those pictures in Cell Discovery in 2024.
A bend in the cell's attachment site, labeled loop 1, changed shape in lab images. That bend moved more freely at one site, helping explain differences between the hormone responses [3].
Retatrutide caused a stronger response than GIP, the body's hormone that prompts insulin release. Retatrutide caused weaker responses than the body's own glucagon and hunger hormones at the other sites.
Those differences describe the drug's action in the lab, rather than better or worse health. Researchers hope to increase calorie burning while limiting the rise in blood sugar.
Pictures of the drug attached to cells aren't tests of lasting safety in people. The studies measuring people's weight and blood tests can tell you more about actual health changes.
Did reviews prove retatrutide prevents heart trouble?
A 2025 review combined 29 studies involving 37,348 adults with excess weight or obesity, without diabetes [7]. The drugs studied act on hormone responses involved in people's hunger and the body's handling of sugar.
Across those drugs, heart and blood-vessel problems were 19% less common than in the comparison groups. Researchers also reported fewer major heart problems, heart attacks and deaths from any cause.
Those findings cover several medicines together, so they don't prove the same protection from retatrutide alone. Retatrutide stood out for better blood fats, but its own heart study remained unfinished [7].
You can't take the combined results as proof that retatrutide will prevent a heart attack. The separate heart study needs to show what happens to people receiving this drug.
Another review, published in 2026, found lower blood pressure with drugs acting on three hormone responses [14]. Both the top and bottom blood pressure readings fell across that group of drugs.
Deaths from any cause were 18% less common, with no extra low blood sugar reported. Nor was extra inflammation reported in the pancreas, the gland near your stomach that makes insulin and helps digest food.
What must the Phase 3 TRIUMPH studies still settle?
Larger Phase 3 studies test lasting benefits and risks that early findings haven't settled. In mid-2026, TRIUMPH weight and diabetes studies expected their main findings in 2026-2027.
Separate studies check whether people receiving retatrutide have fewer serious heart and blood-vessel problems. Another follows kidney disease to learn whether the kidneys lose their function more slowly.
Researchers are also comparing retatrutide directly with tirzepatide, using the same study conditions for both drugs. The earlier separate testing cannot establish whether one drug would give you better results.
Longer follow-up must also show whether weight remains lower over time and what happens after stopping. Completed findings can answer those questions more firmly than guesses based on early weight loss.