Retatrutide: Trial Results, Side Effects, and When You Could Get It
Retatrutide is Eli Lilly's investigational once-weekly triple-agonist injection that produced up to 28.3% (70.3 lbs) average weight loss at 80 weeks in Phase 3. It is not FDA approved, cannot be prescribed, and Lilly plans to file for U.S. approval in Q1 2027.
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Retatrutide is an investigational once-weekly injection from Eli Lilly, listed in the federal clinical trial registry under the development code LY3437943 [6], that activates three hormone receptors at once — GIP, GLP-1, and glucagon — in a single molecule [1][3][4]. In its main Phase 3 trial, people taking the highest studied dose, 12 mg, lost an average of 28.3% of body weight (70.3 lbs) over 80 weeks, and in a pre-specified blinded extension, participants originally assigned to 12 mg who had a baseline BMI of at least 35 lost an average of 30.3% (85.0 lbs) at 104 weeks [1][2]. It is not approved by the FDA, cannot be prescribed, and cannot be legally sold or marketed for human use; Lilly says it plans to submit a Biologics License Application (BLA) to the FDA in Q1 2027 [3][4].
This page is informational only, not medical advice. Retatrutide is investigational, and no dose, titration schedule, or treatment decision should be based on it.
What is retatrutide and how is it different from Zepbound and Wegovy?
Retatrutide is what Lilly calls a first-in-class GIP, GLP-1, and glucagon triple hormone receptor agonist — one molecule that activates receptors for all three hormones [1][3]. Lilly, the maker of Zepbound (tirzepatide) and Foundayo (orforglipron), is developing it [1][3][4]. An indirect-comparison review has projected retatrutide ahead of the maximum evaluated doses of tirzepatide and subcutaneous semaglutide, but that is a projection rather than a head-to-head result [2].
Retatrutide is given once weekly [1][3]. Lilly’s July 2026 release calls retatrutide “an investigational molecule that cannot be legally sold or marketed for human use” [3][4]. In its May 2026 release, Lilly stated the drug is legally available only to participants in its clinical trials [1].
How much weight did people lose in the TRIUMPH-1 trial?
TRIUMPH-1 (NCT05929066) was a Phase 3, 80-week, randomized, double-blind, placebo-controlled master trial in adults with obesity or overweight plus at least one weight-related comorbidity, and without diabetes [1][2]. It randomized 2,339 participants in a 1:1:1:1 ratio to retatrutide 4 mg, 9 mg, 12 mg, or placebo [1][2]. Topline results were announced on May 21, 2026 [1][2]. The lead investigator was Ania Jastreboff, M.D., Ph.D., of the Yale School of Medicine [1].
Participants started at an average weight of 112.7 kg (248.5 lbs) with a BMI of 40.0 [1][2]. The headline numbers below come from the efficacy estimand — the result had all randomized participants stayed on treatment without prohibited weight-management therapies [3][4]:
| TRIUMPH-1, 80 weeks (efficacy estimand) | Retatrutide 4 mg | Retatrutide 9 mg | Retatrutide 12 mg | Placebo |
|---|---|---|---|---|
| Average weight change [1][2] | −19.0% (−47.2 lbs) | −25.9% (−64.4 lbs) | −28.3% (−70.3 lbs) | −2.2% (−5.5 lbs) [1] |
| Lost ≥25% of body weight [1] | 27.8% | 52.9% | 62.5% | 2.2% |
| Lost ≥30% of body weight [1][2] | 15.3% | 37.9% | 45.3% | 0.5% |
| Lost ≥35% of body weight [1] | 5.9% | 20.8% | 27.2% | 0.3% |
The 45.3% of participants on 12 mg who lost at least 30% of their body weight is a level Lilly notes has long been associated with bariatric surgery [1]. Also, 65.3% of participants on 12 mg reached a BMI under 30 by week 80, including 37.5% of those who started with class 3 obesity (BMI ≥40); Lilly notes the BMI <30 analysis was pre-specified but not controlled for multiplicity, and the BMI ≥40 subgroup was assessed after the fact (post hoc) [1][2].
Waist circumference fell by an average of 24.1 cm (9.5 in) on 12 mg, from a baseline of 118.3 cm (46.6 in); the 4 mg and 9 mg groups saw reductions of 16.3 cm and 21.8 cm, versus 3.6 cm for placebo [1][2]. Lilly also reported improvements in non-HDL cholesterol, triglycerides, systolic blood pressure, and high-sensitivity C-reactive protein (hsCRP) [1][2].
As trial design facts only: participants assigned to retatrutide started at 2 mg once weekly and increased in steps every four weeks until reaching their assigned target dose, with the 4 mg target reached through a single escalation step [1].
Why are there two sets of weight-loss numbers?
Lilly reported TRIUMPH-1 two ways. The efficacy estimand represents efficacy had all randomized participants remained on the study intervention, with possible dose interruptions and modifications, without initiating prohibited weight-management treatments [3][4]. Lilly also reported the same endpoints using a treatment-regimen estimand, which produced somewhat smaller figures [1].
Under the treatment-regimen estimand at 80 weeks, weight changes were −17.6% (−43.7 lbs) on 4 mg, −23.7% (−58.9 lbs) on 9 mg, −25.0% (−62.1 lbs) on 12 mg, and −3.9% (−9.7 lbs) on placebo [1]. At 104 weeks in the extension, the treatment-regimen figures were −25.7% (4 mg escalated to maximum tolerated dose), −28.7% (9 mg to maximum tolerated dose), −29.9% (−83.9 lbs, 12 mg to maximum tolerated dose), and −18.9% (placebo switched to retatrutide at maximum tolerated dose) [1]. The two estimands answer different questions and should not be used interchangeably.
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 main 80-week study, and tolerated their assigned dose [1][2]. The extension added 24 more weeks, with blinded escalation to a maximum tolerated dose of 9 mg or 12 mg [1].
Extension participants started heavier, at an average of 121.7 kg (268.3 lbs; BMI 42.8) [1][2]. At 104 weeks, by the efficacy estimand, those originally assigned to 12 mg lost an average of 30.3% (−85.0 lbs) [1][2]; the 9 mg group lost 29.5% (−80.7 lbs), the 4 mg group lost 27.9% (−73.3 lbs), and the placebo group, switched to retatrutide at maximum tolerated dose, lost 19.2% (−49.9 lbs) [1].
Does retatrutide work for people with type 2 diabetes?
Yes, by the trial’s primary endpoint. Lilly reported TRIUMPH-2 (NCT05929079) on July 23, 2026 — a Phase 3, 80-week, randomized, double-blind, placebo-controlled basket-design trial in 1,152 adults with type 2 diabetes and obesity or overweight, randomized 1:1:1:1 to 4 mg, 9 mg, 12 mg, or placebo [3][4]. Lilly frames type 2 diabetes as a population with greater difficulty losing weight [3][4].
Participants averaged 106.4 kg (234.6 lbs; BMI 38.2) at baseline [3][4]. At 80 weeks (efficacy estimand): 4 mg −12.7% (−29.8 lbs); 9 mg −19.1% (−45.4 lbs); 12 mg −20.8% (−49.6 lbs); placebo −4.0% (−9.3 lbs) [3][4]. A1C fell from a baseline of 7.7% by 1.4 points on 4 mg, 1.6 on 9 mg, and 1.5 on 12 mg, versus 0.2 on placebo [3][4].
What about severe obesity plus heart disease (TRIUMPH-3)?
TRIUMPH-3 (NCT05882045) was an 80-week, randomized, double-blind, placebo-controlled trial in 1,949 adults with severe obesity (BMI ≥35) and established cardiovascular disease, randomized 1:1:2 to 9 mg, 12 mg, or placebo [3][4].
Participants averaged 111.4 kg (245.6 lbs; BMI 40.4) at baseline [3][4]. At 80 weeks (efficacy estimand): 9 mg −21.6% (−52.7 lbs); 12 mg −22.6% (−55.8 lbs); placebo −3.2% (−7.7 lbs) [3][4].
On the 12 mg dose, Lilly reported average reductions of 37.0% in triglycerides, 16.5% in non-HDL cholesterol, 9.3 mmHg in systolic blood pressure, 19.0 cm (7.5 in) in waist circumference, and 51.2% in hsCRP [3][4].
Did retatrutide reduce heart attacks and strokes?
The trial did not show a clear answer either way. Major adverse cardiovascular events (MACE) occurred less often than anticipated in both the retatrutide and placebo arms [3][4]. 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 participants randomized to retatrutide (9 mg and 12 mg pooled) versus 52 on placebo, a hazard ratio of 0.82 with a 95% confidence interval of 0.55 to 1.22 [3][4]. For MACE-3 (cardiovascular death, heart attack, or stroke), there were 27 events on retatrutide versus 23 on placebo, a hazard ratio of 1.12 (95% CI 0.64 to 1.96) [3][4].
Both confidence intervals cross 1.0, meaning neither a benefit nor a harm was established. An on-treatment analysis, which Lilly notes was not pre-specified, produced hazard ratios of 0.73 (0.47 to 1.12) for MACE-5 and 0.92 (0.51 to 1.65) for MACE-3 [3][4]. A separate outcomes trial, TRIUMPH-Outcomes (NCT06383390), is registered on ClinicalTrials.gov as studying retatrutide’s effect on cardiovascular and kidney outcomes in adults living with obesity; detailed enrollment and completion dates were not retrievable in the supplied registry text [7].
What are the most common retatrutide side effects?
The side-effect types were generally consistent with other incretin-based therapies, Lilly said, and were mostly gastrointestinal [1][3]. In TRIUMPH-1:
| Adverse event, TRIUMPH-1 | 4 mg | 9 mg | 12 mg | Placebo |
|---|---|---|---|---|
| Nausea [1][2] | 28.6% | 38.4% | 42.4% | 14.8% |
| Diarrhea [1][2] | 25.2% | 34.1% | 32.0% | 13.5% |
| Constipation [1][2] | 23.8% | 25.9% | 26.1% | 10.9% |
| Vomiting [1][2] | 10.6% | 22.8% | 25.3% | 4.8% |
| Upper respiratory tract infection [1] | 14.2% | 12.2% | 13.1% | 11.6% |
| Dysesthesia [1] | 5.1% | 12.3% | 12.5% | 0.9% |
| Urinary tract infection [1] | 7.5% | 8.8% | 8.4% | 5.3% |
Discontinuation due to adverse events in TRIUMPH-1 was 4.1% on 4 mg, 6.9% on 9 mg, and 11.3% on 12 mg, versus 4.9% on placebo — with the 4 mg group below placebo [1][2]. In TRIUMPH-2, discontinuation rates were 3.8% (4 mg), 11.6% (9 mg), and 7.7% (12 mg) versus 4.9% on placebo; in TRIUMPH-3 they were 9.8% (9 mg) and 13.5% (12 mg) versus 4.8% on placebo [3][4].
Dysesthesia occurred in 4.5%, 5.6%, and 7.3% of TRIUMPH-2 participants on 4 mg, 9 mg, and 12 mg versus 0.7% on placebo, and in 6.4% and 6.4% on 9 mg and 12 mg in TRIUMPH-3 versus 1.3% on placebo [3][4]. Lilly said dysesthesia and urinary tract infections were generally mild to moderate and the majority resolved during treatment [3][4]; in TRIUMPH-1, Lilly also noted that most participants continued taking retatrutide [1].
When will retatrutide be FDA approved?
No application has been filed with the FDA as of Lilly’s July 23, 2026 release [3][4]. Lilly says it is completing the Chemistry, Manufacturing, and Controls (CMC) data package required for a BLA and plans to submit retatrutide in Q1 2027 for U.S. approval [3][4].
The FDA’s published description of its review process — written for the New Drug Application (NDA) pathway — says that once an application is complete, the review team has 6 to 10 months to decide whether to approve the drug [5]. Lilly’s retatrutide application will be a BLA rather than an NDA [3][4], so this window is the FDA’s stated NDA timeline, not a published BLA-specific clock for retatrutide. The FDA can also require the developer to answer questions on existing data or run additional studies before approval, and it may convene an advisory committee when questions arise [5].
Any estimate of when retatrutide could reach pharmacies is therefore arithmetic, not guidance: Lilly’s Q1 2027 filing target (January through March 2027) plus the FDA’s stated 6-to-10-month review window points to a decision roughly between mid-2027 and early 2028, if the application is filed on schedule, accepted as complete, and approved without major delays. Neither Lilly nor the FDA has published an approval or launch date.
How does retatrutide compare with Zepbound and Wegovy right now?
There is no head-to-head trial result comparing retatrutide with tirzepatide or semaglutide in the available information; the comparisons that exist are cross-trial or indirect, with different populations, durations, and estimands [1][2].
One indirect-comparison review published in the Annals of Internal Medicine, covering 26 randomized controlled trials of 12 GLP-1 receptor agonists and coagonists in 15,491 adults without diabetes, projected 24.2% weight loss for retatrutide 12 mg, versus 17.8% for the maximum evaluated dose of tirzepatide and 13.9% for subcutaneous semaglutide [2]. Projections are not the same as a direct comparison.
A head-to-head Phase 3 study of retatrutide compared with tirzepatide in adults who have obesity is registered on ClinicalTrials.gov as NCT06662383; registry detail beyond the title was not retrievable in the supplied text [6].
How can I get retatrutide legally before approval?
Clinical trial participation is the route Lilly itself names: in its May 2026 release, the company stated retatrutide is legally available only to participants in Lilly’s clinical trials [1]. ClinicalTrials.gov is the registry where retatrutide studies and their contact and location details are posted [6][7][8]. Among the registered records is SYNERGY-Outcomes (NCT07165028), listed on the registry as a master protocol of multiple agents in adults with metabolic dysfunction-associated steatotic liver disease; its recruiting status and enrollment target were not retrievable in the supplied registry text [8].
Expanded access, also called compassionate use, is a separate FDA-described route for patients with serious diseases or conditions who cannot participate in a clinical trial to gain access to a product not yet approved by the FDA [6]. The FDA describes three types: Individual Patients, Intermediate-size Population, and Treatment IND/Protocol [6]. A registry status of “Available” for expanded access means patients who are not study participants may be able to gain access [6]. A retatrutide expanded access record exists at NCT07629401, but its eligibility criteria and contact details were not retrievable in the supplied source text [11].
Why is retatrutide not available for sale?
Lilly states plainly that retatrutide cannot be legally sold or marketed for human use [3][4]. Because no retatrutide product has been approved anywhere, there is no legitimate pharmaceutical supply of it [1][3]. The FDA has separately published concerns about unapproved GLP-1 drugs used for weight loss [9].
What can I do while waiting for approval?
Lilly already markets two approved options in the United States: Zepbound (tirzepatide) and Foundayo (orforglipron) [1][3][4]. Foundayo is a prescription medicine used with a reduced-calorie diet and increased physical activity to help adults with obesity, or some adults with overweight who also have weight-related medical problems, lose excess body weight and keep it off [3][4].
Foundayo’s labeling carries a warning that it may cause tumors in the thyroid, including thyroid cancer, and it is contraindicated for people with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 [3][4]. Foundayo should not be used with other GLP-1 receptor agonist medicines, and it is not known whether it is safe and effective in children [3][4]. Whether any approved medicine is appropriate is a decision for a healthcare provider.
What other retatrutide data is still coming?
The TRIUMPH Phase 3 program began in 2023 and has enrolled more than 5,800 participants across four global registrational trials, covering obesity or overweight, moderate-to-severe obstructive sleep apnea with obesity, and knee osteoarthritis pain [1][3][4]. TRIUMPH-1 also included basket trials for knee osteoarthritis pain and obstructive sleep apnea, with those analyses to be released separately [1].
Lilly’s broader Phase 3 study list for retatrutide covers obesity or overweight, type 2 diabetes, knee osteoarthritis pain, moderate-to-severe obstructive sleep apnea, chronic low back pain, cardiovascular and renal outcomes, and metabolic dysfunction-associated steatotic liver disease [1][3][4]. As of July 2026, Lilly counts five positive Phase 3 studies to date and says it now has the clinical data package to support global submissions for obesity, knee osteoarthritis pain, and obstructive sleep apnea [3][4]. Detailed TRIUMPH-1 data are slated for presentation at the 86th annual American Diabetes Association Scientific Sessions [1][2].
Sources
- Eli Lilly and Company. Lilly’s triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial. May 21, 2026.
- AJMC. Retatrutide achieves up to 30.3% average weight loss in Phase 3 TRIUMPH-1 trial. May 21, 2026.
- 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.
- PR Newswire. Lilly’s triple agonist, retatrutide, successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1C. July 23, 2026.
- US Food and Drug Administration. Step 4: FDA drug review.
- ClinicalTrials.gov. A study of retatrutide (LY3437943) compared to tirzepatide (LY3298176) in adults who have obesity. Study NCT06662383.
- ClinicalTrials.gov. The effect of retatrutide once weekly on cardiovascular outcomes and kidney outcomes in adults living with obesity (TRIUMPH-Outcomes). Study NCT06383390.
- ClinicalTrials.gov. A master protocol of multiple agents in adults with metabolic dysfunction-associated steatotic liver disease (SYNERGY-Outcomes). Study NCT07165028.
- US Food and Drug Administration. FDA’s concerns with unapproved GLP-1 drugs used for weight loss.
- ClinicalTrials.gov. A study of retatrutide (LY3437943) in participants who have obesity or overweight. Study NCT05929066.
- ClinicalTrials.gov. Clinical trial study record, NCT07629401.
Frequently asked questions
Is retatrutide FDA approved yet?
No. As of Lilly's July 23, 2026 release, no application had been filed with the FDA. Lilly plans to submit a Biologics License Application in Q1 2027. The FDA's published 6-to-10-month review window is described for the NDA process, not a BLA-specific clock for retatrutide.
Can I buy retatrutide legally right now?
No. Lilly states retatrutide is an investigational molecule that cannot be legally sold or marketed for human use, and that it is legally available only to participants in Lilly's clinical trials. No approved retatrutide product exists anywhere, so there is no legitimate supply.
How much weight do people lose on retatrutide versus tirzepatide?
No head-to-head result exists. In TRIUMPH-1, the 12 mg dose produced 28.3% (70.3 lbs) average weight loss at 80 weeks. An indirect-comparison review projected 24.2% for retatrutide 12 mg versus 17.8% for maximum-dose tirzepatide and 13.9% for subcutaneous semaglutide, but that is a projection, not a direct comparison.
What doses of retatrutide were studied?
TRIUMPH-1 studied 4 mg, 9 mg, and 12 mg once weekly versus placebo in 2,339 adults; TRIUMPH-2 studied the same three doses; TRIUMPH-3 studied 9 mg and 12 mg. These are trial design facts, not dosing guidance for any individual.
What are the most common retatrutide side effects?
In TRIUMPH-1, the most common were nausea (up to 42.4% on 12 mg), diarrhea (up to 34.1%), constipation (up to 26.1%), and vomiting (up to 25.3%), all versus much lower placebo rates. Discontinuation for adverse events was 4.1%, 6.9%, and 11.3% on 4, 9, and 12 mg versus 4.9% on placebo.
How often did dysesthesia occur in the trials?
In TRIUMPH-1, dysesthesia occurred in 5.1%, 12.3%, and 12.5% of participants on 4, 9, and 12 mg versus 0.9% on placebo. Lilly said these events were generally mild to moderate and mostly resolved during treatment.
Does retatrutide work for people with type 2 diabetes?
Yes, by the primary endpoint. In TRIUMPH-2, participants lost 12.7%, 19.1%, and 20.8% of body weight on 4, 9, and 12 mg versus 4.0% on placebo at 80 weeks, with A1C falling up to 1.6 points from a baseline of 7.7%.
Did retatrutide reduce heart attacks and strokes?
It was not established either way. In TRIUMPH-3, MACE-5 showed a hazard ratio of 0.82 (95% CI 0.55 to 1.22) and MACE-3 a hazard ratio of 1.12 (95% CI 0.64 to 1.96); both confidence intervals cross 1.0, and events were fewer than anticipated in both arms.
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.