Retatrutide: Weight Loss Results, Side Effects, and When It Could Be Approved
Retatrutide is Eli Lilly's investigational once-weekly triple agonist (GIP, GLP-1, glucagon). In the Phase 3 TRIUMPH-1 trial, the 12 mg dose produced 28.3% (70.3 lbs) average weight loss at 80 weeks. Lilly plans to file for FDA approval in Q1 2027.
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Retatrutide is an investigational once-weekly injection from Eli Lilly — a single molecule that activates three hormone receptors at once: GIP, GLP-1, and glucagon [1][2][3]. It is not FDA approved, and Lilly states it cannot be legally sold or marketed for human use [1]. The largest weight-loss result announced so far comes from the Phase 3 TRIUMPH-1 trial: participants on the 12 mg dose lost an average of 70.3 lbs (28.3% of body weight) over 80 weeks, and those who continued into a 104-week extension lost up to 85.0 lbs (30.3%) [2][4]. These are topline results from company announcements; Lilly states detailed results will be presented at medical meetings and published in peer-reviewed journals [1][2]. As for when you can get it: Lilly has committed only to submitting a Biologics License Application (BLA) to the FDA in Q1 2027, after it finishes its manufacturing (CMC) data package. No approval or launch date has been announced [1].
What does “triple agonist” mean?
Retatrutide is a first-in-class “triple agonist”: one molecule that activates receptors for glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon [1][2][3]. That distinguishes it from drugs already on the market. Semaglutide works on the GLP-1 receptor alone, and tirzepatide is a dual GLP-1/GIP agonist. The American Diabetes Association has described retatrutide as “the next in the string of game-changing metabolic agents” that began with semaglutide and continued with tirzepatide [6].
The sources describe which receptors the drug targets, not a proven mechanism for why it produces weight loss. Trial investigators frame the condition it treats as chronic: “Obesity is a chronic disease, and people living with obesity deserve treatment options that match the complex biology of their neurometabolic disease,” said TRIUMPH-1 lead investigator Ania Jastreboff, MD, PhD, of Yale School of Medicine [2][7].
How much weight did people lose in the main obesity trial?
TRIUMPH-1 (NCT05929066), announced May 21, 2026, was an 80-week randomized, double-blind, placebo-controlled trial in adults with obesity or overweight, at least one weight-related comorbidity, and no diabetes. It randomized 2,339 participants 1:1:1:1 to retatrutide 4 mg, 9 mg, 12 mg, or placebo. Average starting weight was 112.7 kg (248.5 lbs) with a BMI of 40.0 [2][4].
Using the efficacy estimand (the effect had everyone stayed on treatment), the results at 80 weeks were [2]:
| Group | Weight change at 80 weeks | ≥25% loss | ≥30% loss | ≥35% loss |
|---|---|---|---|---|
| Retatrutide 4 mg | -19.0% (-47.2 lbs) | 27.8% | 15.3% | 5.9% |
| Retatrutide 9 mg | -25.9% (-64.4 lbs) | 52.9% | 37.9% | 20.8% |
| Retatrutide 12 mg | -28.3% (-70.3 lbs) | 62.5% | 45.3% | 27.2% |
| Placebo | -2.2% (-5.5 lbs) | 2.2% | 0.5% | 0.3% |
Lilly and AJMC both framed the ≥30% threshold as a level historically associated with bariatric surgery [2][4]. Waist circumference fell by an average of 24.1 cm (9.5 in) in the 12 mg group, from a baseline of 118.3 cm [2][4].
A separate treatment-regimen estimand, which reflects what happened regardless of whether people stayed on the drug, showed smaller but still large reductions: -17.6% (4 mg), -23.7% (9 mg), -25.0% (12 mg), versus -3.9% for placebo [2].
One figure that got wide attention: 65.3% of participants on 12 mg ended the trial with a BMI under 30, dropping below the obesity threshold. That analysis was pre-specified but not controlled for multiplicity, and the related figure for people who started with class 3 obesity (BMI ≥40) — 37.5% — was post-hoc [2].
What happened in the 104-week extension?
TRIUMPH-1 included a pre-specified blinded extension for 532 participants who had a baseline BMI of at least 35, completed the 80-week main study, and tolerated their dose. They continued for 24 more weeks, with blinded escalation to a maximum tolerated dose of 9 mg or 12 mg [2][4].
By 104 weeks, from an average baseline of 121.7 kg (268.3 lbs; BMI 42.8), weight loss was [2]:
| Group (escalated to max tolerated dose) | Weight change at 104 weeks |
|---|---|
| Started on 4 mg | -27.9% (-73.3 lbs) |
| Started on 9 mg | -29.5% (-80.7 lbs) |
| Started on 12 mg | -30.3% (-85.0 lbs) |
| Placebo, then switched to retatrutide | -19.2% (-49.9 lbs) |
The extension covers only people with BMI ≥35 who had already completed 80 weeks and tolerated the drug, so it does not represent the full trial population [2][4].
Did it work for people with type 2 diabetes?
TRIUMPH-2 (NCT05929079), announced July 23, 2026, tested retatrutide in 1,152 adults with type 2 diabetes and obesity or overweight, randomized 1:1:1:1 over 80 weeks. Lilly noted this population has increased difficulty losing weight. Average starting weight was 106.4 kg (234.6 lbs), BMI 38.2 [1].
At 80 weeks, weight loss was -12.7% (-29.8 lbs) on 4 mg, -19.1% (-45.4 lbs) on 9 mg, and -20.8% (-49.6 lbs) on 12 mg, versus -4.0% (-9.3 lbs) on placebo. A1C fell from a baseline of 7.7% by -1.4% (4 mg), -1.6% (9 mg), and -1.5% (12 mg), versus -0.2% on placebo. The trial included a four-week post-treatment follow-up period [1].
What about severe obesity with cardiovascular disease?
TRIUMPH-3 (NCT05882045), also announced July 23, 2026, enrolled 1,949 adults with severe obesity (BMI ≥35) and established cardiovascular disease, with or without type 2 diabetes, randomized 1:1:2 to 9 mg, 12 mg, or placebo for 80 weeks. Average starting weight was 111.4 kg (245.6 lbs), BMI 40.4 [1].
Weight loss was -21.6% (-52.7 lbs) on 9 mg and -22.6% (-55.8 lbs) on 12 mg, versus -3.2% (-7.7 lbs) on placebo. At the highest dose, the trial also showed reductions in cardiovascular risk factors: triglycerides down 37.0%, non-HDL cholesterol down 16.5%, systolic blood pressure down 9.3 mmHg, waist circumference down 7.5 in (19.0 cm), and hsCRP down 51.2% [1].
On heart attacks and strokes specifically, the results do not show proven benefit. Major adverse cardiovascular events (MACE) occurred less frequently than anticipated in both arms. In the pre-specified in-study analysis, there were 44 MACE-5 events (all-cause death, heart attack, stroke, heart failure event, or coronary revascularization) among retatrutide participants versus 52 on placebo, a hazard ratio of 0.82 (95% CI 0.55–1.22). For MACE-3 (cardiovascular death, heart attack, stroke), there were 27 events with retatrutide versus 23 with placebo, a hazard ratio of 1.12 (95% CI 0.64–1.96). Both confidence intervals cross 1.0, meaning neither a benefit nor a harm was established. An on-treatment analysis showing a hazard ratio of 0.73 for MACE-5 was not pre-specified [1].
Did it help knee osteoarthritis pain?
TRIUMPH-4 (NCT05931367), announced December 11, 2025, was the first Phase 3 readout. It randomized 445 adults with obesity or overweight (BMI ≥27) and knee osteoarthritis, without diabetes, 1:1:1 to 9 mg, 12 mg, or placebo for 68 weeks. Most participants — 84.0% — had a baseline BMI of at least 35 [3][6].
Weight loss was -26.4% (-64.2 lbs) on 9 mg and -28.7% (-71.2 lbs) on 12 mg, versus -2.1% on placebo. On the co-primary pain endpoint, the WOMAC pain subscale fell by 4.5 points from a baseline of 6.0 on 9 mg and 4.4 points on 12 mg, versus 2.4 points on placebo. The percent-change figures (-75.8%, -74.3%, -40.3%) were post-hoc. WOMAC physical function scores improved by 4.1 and 4.2 points versus 2.1 for placebo. On the ≥70% WOMAC pain reduction endpoint, 73.0% (9 mg) and 67.7% (12 mg) qualified versus 26.2% on placebo — though that endpoint was not controlled for multiplicity [3]. In a post-hoc analysis, 14.1% (9 mg) and 12.0% (12 mg) were completely free of knee pain at 68 weeks versus 4.2% on placebo. Systolic blood pressure fell 14.0 mmHg at the highest dose, though that figure was not controlled for multiplicity [3][6].
What doses were used in the trials?
The TRIUMPH program studied five doses of retatrutide: 2 mg, 4 mg, 6 mg, 9 mg, and 12 mg. Across all studies, everyone randomized to the drug started at 2 mg once weekly and increased the dose every four weeks until reaching their assigned target [1][3].
Target doses differed by trial: TRIUMPH-1 and TRIUMPH-2 tested 4 mg, 9 mg, and 12 mg; TRIUMPH-3 and TRIUMPH-4 tested 9 mg and 12 mg [3]. The 4 mg target was reached with a single escalation step [2]. These are investigational doses assigned under trial protocols, not prescribing guidance — no approved dosing exists because no application has been approved [1].
What are the side effects?
The side-effect profile was generally consistent with other incretin-based therapies, dominated by gastrointestinal effects that increased with dose [1][2][3]. In TRIUMPH-1, the most common adverse events were [2]:
| Adverse event | 4 mg | 9 mg | 12 mg | Placebo |
|---|---|---|---|---|
| Nausea | 28.6% | 38.4% | 42.4% | 14.8% |
| Diarrhea | 25.2% | 34.1% | 32.0% | 13.5% |
| Constipation | 23.8% | 25.9% | 26.1% | 10.9% |
| Vomiting | 10.6% | 22.8% | 25.3% | 4.8% |
| Upper respiratory tract infection | 14.2% | 12.2% | 13.1% | 11.6% |
TRIUMPH-2 and TRIUMPH-3 showed similar patterns. In TRIUMPH-2, diarrhea ranged from 27.4% to 33.6% across doses versus 13.2% on placebo; nausea ranged from 13.7% to 28.0% versus 8.0%. In TRIUMPH-3, diarrhea was 30.1% (9 mg) and 24.4% (12 mg) versus 8.7% on placebo, and hyperglycemia was actually less common with retatrutide (3.9% and 3.1%) than placebo (13.4%) [1].
One side effect stands out as distinctive: dysesthesia, an unusual or unpleasant skin sensation. In TRIUMPH-1 it occurred in 5.1%, 12.3%, and 12.5% of participants on 4 mg, 9 mg, and 12 mg versus 0.9% on placebo [2]. In TRIUMPH-2 it ranged from 4.5% to 7.3% versus 0.7% on placebo, and in TRIUMPH-3 it was 6.4% on both doses versus 1.3% on placebo. Lilly states these events were generally mild to moderate and the majority resolved during treatment [1]. In TRIUMPH-4, dysesthesia was reported by 8.8% on 9 mg and 20.9% on 12 mg versus 0.7% on placebo, and was generally mild and rarely led to discontinuation [3][5].
Urinary tract infections were also tracked: 7.5–8.8% across retatrutide doses in TRIUMPH-1 versus 5.3% on placebo, 3.8–8.0% in TRIUMPH-2 versus 6.6% on placebo, and 6.1–7.0% in TRIUMPH-3 versus 5.3% on placebo [1][2].
How many people stopped the drug because of side effects?
Discontinuation rates due to adverse events rose with dose in most trials [1][2][3]:
| Trial | 4 mg | 9 mg | 12 mg | Placebo |
|---|---|---|---|---|
| TRIUMPH-1 | 4.1% | 6.9% | 11.3% | 4.9% |
| TRIUMPH-2 | 3.8% | 11.6% | 7.7% | 4.9% |
| TRIUMPH-3 | — | 9.8% | 13.5% | 4.8% |
| TRIUMPH-4 | — | 12.2% | 18.2% | 4.0% |
In TRIUMPH-4, Lilly said the discontinuation rates were highly correlated with baseline BMI and included some people stopping for perceived excessive weight loss. Among the subgroup with baseline BMI ≥35, rates were 8.8% (9 mg) and 12.1% (12 mg) versus 4.8% on placebo [3].
Is retatrutide better than tirzepatide or semaglutide?
There are no head-to-head trials in the available reporting, so any comparison across drugs is indirect [2][3][4]. The closest thing is a network review published in Annals of Internal Medicine, which analyzed 12 GLP-1 receptor agonists and coagonists across 26 randomized controlled trials involving 15,491 adults without diabetes. It projected 24.2% weight loss for retatrutide 12 mg, versus 17.8% for tirzepatide and 13.9% for subcutaneous semaglutide at their maximum evaluated doses [4].
Earlier Phase 2 data published in the New England Journal of Medicine showed up to 24.2% mean weight loss at 48 weeks [7]. The Phase 3 results exceeded that, but cross-trial comparisons have limits: different populations, durations, and designs. Lilly already markets two approved obesity medicines, Zepbound (tirzepatide) and Foundayo (orforglipron) [1][2].
When will retatrutide be available in the US?
The only firm date Lilly has given is a planned BLA submission to the FDA in Q1 2027, after the company completes its Chemistry, Manufacturing, and Controls (CMC) data package [1]. Lilly has not stated an approval or launch date, and no review timeline can be projected from the available sources [1].
Lilly says it now has the clinical data package to support global submissions for obesity, knee osteoarthritis pain, and obstructive sleep apnea [1]. The TRIUMPH program began in 2023 and spans four global registrational trials with more than 5,800 participants enrolled [1][2][3]. As of July 23, 2026, Lilly counted five positive Phase 3 studies [1]. Other Phase 3 areas still under study include type 2 diabetes, chronic low back pain, cardiovascular and renal outcomes, and metabolic dysfunction-associated steatotic liver disease [1][2][3]. Detailed TRIUMPH-1 data are slated for presentation at the 86th annual American Diabetes Association Scientific Sessions [2][4].
Can you buy retatrutide online?
No — not legally, according to Lilly. The company states retatrutide is an investigational molecule that cannot be legally sold or marketed for human use [1]. An earlier Lilly release put it more directly: the drug is legally available only to participants in Lilly’s clinical trials [2]. Products sold online as “research use only” retatrutide fall outside that, and because no BLA has been filed, there is no FDA-approved label, dose, or warning information for the drug [1].
What does this mean if you want treatment now?
Retatrutide produced the largest weight reductions in the Phase 3 obesity data announced so far — 28.3% at 80 weeks and 30.3% at 104 weeks in the BMI ≥35 extension — but it remains an investigational weekly injection with dose-dependent gastrointestinal side effects and discontinuations [1][2][3][4]. It cannot be prescribed. Lilly’s approved options referenced in its releases are Zepbound and Foundayo [1][2]. Anyone weighing obesity treatment options should talk with a clinician about what is currently approved and available.
Sources
- Eli Lilly and Company. 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 and Company. Lilly’s triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial. May 21, 2026.
- Eli Lilly and Company. 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.
- AJMC. Retatrutide achieves up to 30.3% average weight loss in Phase 3 TRIUMPH-1 trial. May 21, 2026.
- Pharmaceutical Executive. Lilly’s retatrutide displays positive topline results in successful Phase III trial. December 11, 2025.
- Patient Care Online. Retatrutide achieves up to 28.7% weight loss and marked knee pain reduction in Phase 3 TRIUMPH-4 trial. December 11, 2025.
- BioPharm International. Lilly reports up to 28.3% weight loss with retatrutide in Phase 3 obesity trial. May 21, 2026.
- Ozmosi. The obesity drug pipeline in 2026: emerging targets, companies and clinical readouts. August 17, 2026.
- PR Newswire. Novo Nordisk files for FDA approval of CagriSema, the first once-weekly combination of GLP-1 and amylin analogues for weight management.
- BioSpace. Novo Nordisk: Triple agonist UBT251 delivers up to 19.7% mean weight loss after 24 weeks in phase 2 trial in China. February 24, 2026.
- HCPLive. TRIUMPH-4: Topline data highlights retatrutide’s significant weight loss effects. March 6, 2026.
Frequently asked questions
Is retatrutide FDA approved?
No. Retatrutide is an investigational drug, and Lilly states it cannot be legally sold or marketed for human use. No Biologics License Application has been approved, so there is no FDA-approved label, dose, or warnings for it. Lilly plans to submit a BLA to the FDA in Q1 2027.
When will retatrutide be available in the US?
No availability date has been announced. Lilly has committed only to submitting a BLA to the FDA in Q1 2027, after completing its manufacturing (CMC) data package. The company says it has the clinical data to support global submissions for obesity, knee osteoarthritis pain, and obstructive sleep apnea.
How much weight did people lose on retatrutide?
In TRIUMPH-1, participants on 12 mg lost an average of 70.3 lbs (28.3%) at 80 weeks, with 45.3% achieving at least 30% weight loss. In a 104-week extension of people with BMI ≥35, average loss reached 85.0 lbs (30.3%). Results were smaller in other populations, such as 20.8% (49.6 lbs) in TRIUMPH-2 with type 2 diabetes.
Is retatrutide better than tirzepatide or semaglutide?
There are no head-to-head trials, so this is not settled. An Annals of Internal Medicine network review of 26 RCTs projected 24.2% weight loss for retatrutide 12 mg versus 17.8% for tirzepatide and 13.9% for subcutaneous semaglutide at maximum evaluated doses. Cross-trial comparisons have limits because populations and designs differ.
What dose of retatrutide was used in trials?
The TRIUMPH program studied 2, 4, 6, 9, and 12 mg doses. Everyone started at 2 mg once weekly and stepped up every four weeks to a target dose: 4, 9, or 12 mg in TRIUMPH-1 and -2, and 9 or 12 mg in TRIUMPH-3 and -4. These are investigational protocol doses, not prescribing guidance.
What is dysesthesia and how often did it happen?
Dysesthesia is an unusual or unpleasant skin sensation. In TRIUMPH-1 it occurred in 5.1% to 12.5% of retatrutide participants versus 0.9% on placebo, and in TRIUMPH-4 it reached 20.9% at the 12 mg dose versus 0.7% on placebo. Lilly reports these events were generally mild to moderate and mostly resolved during treatment.
Does retatrutide help type 2 diabetes blood sugar?
In TRIUMPH-2, adults with type 2 diabetes and obesity saw A1C drop from a 7.7% baseline by 1.4 to 1.6 percentage points across retatrutide doses, versus 0.2 on placebo, alongside weight loss up to 20.8% (49.6 lbs) at 80 weeks. Retatrutide is not approved for diabetes or any other use.
Did retatrutide reduce heart attacks and strokes?
That was not established. In TRIUMPH-3, the pre-specified MACE-5 analysis showed a hazard ratio of 0.82 (95% CI 0.55–1.22) and MACE-3 showed 1.12 (95% CI 0.64–1.96) — both confidence intervals cross 1.0. An on-treatment analysis favoring retatrutide was not pre-specified. Risk factors like triglycerides and blood pressure did improve.
This article summarizes FDA labeling, published research and company information current as of September 14, 2026. It is not medical advice and does not replace a conversation with your own healthcare provider. How we research and verify.