Research checked November 4, 2026: TRIUMPH-2 results were subsequently published in The Lancet. In a separate October announcement, Lilly reported topline TRANSCEND-T2D-2 results comparing retatrutide with semaglutide in adults with type 2 diabetes. The head-to-head results remain company-reported; retatrutide remains investigational.
TRANSCEND-T2D-2 context: In Lilly’s open-label Phase 3 study of 1,298 adults with type 2 diabetes, the company reported 80-week mean weight reductions of 19.5% and 20.9% in the two retatrutide groups versus 9.4% with semaglutide, using the efficacy estimand. Adverse-event discontinuations were 4.8% and 7.9% versus 2.7%, respectively. These company-reported topline findings are from a different study than TRIUMPH and do not establish approval or a use for laboratory reference materials.
In a separate study of adults with obesity without diabetes, Jastreboff and the TRIUMPH-1 investigators reported a 25.0% mean body-weight reduction in the highest studied group versus 3.9% with placebo at 80 weeks, using the treatment-regimen estimand. This is a different trial and population from TRIUMPH-2 and TRIUMPH-3, so the results should not be treated as a head-to-head comparison. For a separate early-stage comparison, read our CT-G32 vs retatrutide rat-study overview. Its animal findings are not equivalent to Phase 3 clinical results.
Researchers also published results from two Phase 3 obstructive sleep apnea studies, reporting changes in apnea-hypopnea measures compared with placebo. These studies address a different research question and population; publication does not establish FDA approval.
November 2026 knee osteoarthritis update: Lilly reported that participants in TRIUMPH-4 receiving retatrutide experienced an average reduction in knee pain of up to 4.5 points from a baseline of 6.0 on the WOMAC pain scale. These are company-reported findings from a study in adults with obesity or overweight and knee osteoarthritis. The November 8 conference abstract describes a 68-week randomized trial with 445 participants and a placebo group. A conference abstract is preliminary evidence; read the group results and analysis method together when comparing outcomes. The reported result does not mean everyone became pain-free or establish an approved use for retatrutide. Lilly’s November announcement did not provide a placebo comparison for its 4.5-point figure.
Eli Lilly has announced positive topline results from two additional Phase 3 clinical trials evaluating investigational retatrutide, further expanding the growing body of research surrounding this triple hormone receptor agonist.
Lilly reported that TRIUMPH-2 and TRIUMPH-3 produced mean body-weight reductions of up to 22.6% at 80 weeks under its efficacy estimand, alongside changes in glucose control and cardiometabolic markers. In July 2026, Lilly announced plans for a biologics application in early 2027. In October, FDA reaffirmed a different classification and stated that an application would follow the drug pathway.
Although retatrutide remains an investigational compound, these latest findings continue to position it among the most closely watched therapies currently being studied for obesity and metabolic disease.
Key Takeaways
- Eli Lilly reported positive topline results from the Phase 3 TRIUMPH-2 and TRIUMPH-3 trials.
- In Lilly’s TRIUMPH-3 report, the highest studied group had a mean weight reduction of 22.6% (55.8 pounds) at 80 weeks under the efficacy estimand. This describes a group average, not an individual prediction.
- Individuals with type 2 diabetes experienced reductions in A1C of up to 1.6 percentage points.
- Researchers observed improvements in triglycerides, blood pressure, waist circumference, non-HDL cholesterol, and inflammatory markers.
- Gastrointestinal events remained the most commonly reported adverse events and were generally consistent with other incretin-based therapies.
- Lilly announced a biologics filing plan in July; FDA’s October decision stated that an application would follow the drug pathway.
What Is Retatrutide?
Retatrutide is an investigational once-weekly peptide being studied for obesity and several metabolic disorders.
Unlike currently approved therapies that activate one or two hormone receptors, retatrutide is designed to activate three separate metabolic pathways simultaneously:
- GLP-1 (Glucagon-Like Peptide-1) receptor
- GIP (Glucose-Dependent Insulinotropic Polypeptide) receptor
- Glucagon receptor
Because of this unique mechanism, retatrutide is commonly referred to as a triple agonist.
Researchers believe activating all three receptors may influence multiple aspects of metabolism, including appetite regulation, energy expenditure, fat metabolism, glucose regulation, and body weight.
| Therapy | Primary Targets |
|---|---|
| Semaglutide | GLP-1 |
| Tirzepatide | GLP-1 + GIP |
| Retatrutide | GLP-1 + GIP + Glucagon |
The addition of glucagon receptor activity distinguishes retatrutide from currently approved dual agonists and has generated significant interest within obesity and metabolic disease research.
TRIUMPH-2: Retatrutide in Obesity and Type 2 Diabetes
TRIUMPH-2 enrolled 1,152 adults living with obesity or overweight who also had type 2 diabetes.
Participants were randomized to receive:
- Retatrutide 4 mg
- Retatrutide 9 mg
- Retatrutide 12 mg
- Placebo
Treatment continued for 80 weeks.
TRIUMPH-2 Weight Loss Results
Average body weight reduction from baseline in Lilly’s efficacy estimand, which estimates outcomes if participants remained on study treatment without starting prohibited weight-management treatments, allowing for dose interruptions and modifications:
In the published TRIUMPH-2 paper, the treatment-regimen analysis, which accounts for participants regardless of treatment discontinuation, reported average weight changes of -11.9%, -16.8%, and -18.8% in the respective retatrutide groups versus -5.1% with placebo at week 80. These estimates answer a different question than the efficacy-estimand figures below. See Bellido and colleagues.
| Treatment | Average Weight Loss |
|---|---|
| Retatrutide 4 mg | 12.7% |
| Retatrutide 9 mg | 19.1% |
| Retatrutide 12 mg | 20.8% |
| Placebo | 4.0% |
Average pounds lost:
- 29.8 pounds (4 mg)
- 45.4 pounds (9 mg)
- 49.6 pounds (12 mg)
- 9.3 pounds (placebo)
Historically, individuals with type 2 diabetes have often experienced smaller average weight reductions than participants without diabetes in obesity studies. Observing average weight reductions exceeding 20% in this population represents a notable finding within the broader clinical development program.
Blood Sugar Control
Participants entered the study with an average A1C of approximately 7.7%.
After 80 weeks:
- 4 mg reduced A1C by 1.4 percentage points
- 9 mg reduced A1C by 1.6 percentage points
- 12 mg reduced A1C by 1.5 percentage points
- Placebo reduced A1C by 0.2 percentage points
These findings suggest retatrutide may influence both body weight and measures of glucose regulation in adults with obesity and type 2 diabetes.
TRIUMPH-3: Severe Obesity and Established Cardiovascular Disease
Lilly’s July 2026 TRIUMPH-3 announcement reported 1,949 randomized participants; the ClinicalTrials.gov record lists actual enrollment of 1,946. The sources do not explain the difference here. The trial population included adults with:
- Severe obesity (BMI ≥35)
- Established cardiovascular disease
- With or without type 2 diabetes
Participants received:
- Retatrutide 9 mg
- Retatrutide 12 mg
- Placebo
Treatment also continued for 80 weeks.
TRIUMPH-3 Weight Loss Results
Average weight reduction from baseline in Lilly’s efficacy estimand:
| Treatment | Average Weight Loss |
|---|---|
| Retatrutide 9 mg | 21.6% |
| Retatrutide 12 mg | 22.6% |
| Placebo | 3.2% |
Average pounds lost:
- 52.7 pounds (9 mg)
- 55.8 pounds (12 mg)
- 7.7 pounds (placebo)
These findings are among the largest average weight reductions reported in large Phase 3 obesity studies to date.
Improvements in Cardiometabolic Risk Markers
Beyond changes in body weight, investigators reported improvements across several cardiometabolic measurements.
At the 12 mg dose, average reductions included:
- Triglycerides: 37.0%
- Non-HDL cholesterol: 16.5%
- Systolic blood pressure: 9.3 mmHg
- Waist circumference: 7.5 inches (19 cm)
- High-sensitivity C-reactive protein (hsCRP): 51.2%
These measurements are commonly evaluated during obesity and metabolic disease research because they are associated with overall cardiometabolic health.
While these findings are encouraging, improvements in individual biomarkers should not automatically be interpreted as evidence of reduced cardiovascular events. Dedicated cardiovascular outcome studies are designed to answer that question.
Cardiovascular Events: What Did Researchers Find?
TRIUMPH-3 also monitored major adverse cardiovascular events (MACE). In its July 2026 report, Lilly presented prespecified in-study analyses comparing the pooled retatrutide groups with placebo. The trial randomized participants 1:1:2 to retatrutide 9 mg, retatrutide 12 mg and placebo. The counts below describe first events, not percentages; the hazard ratios account for time to event.
Researchers evaluated two commonly used composite endpoints.
MACE-5
Included:
- All-cause death
- Heart attack
- Stroke
- Heart failure events
- Coronary revascularization
Results:
- 44 events among participants randomized to the pooled retatrutide groups
- 52 events in the placebo group
Hazard Ratio:
0.82 (95% confidence interval 0.55 to 1.22)
MACE-3
Included:
- Cardiovascular death
- Heart attack
- Stroke
Results:
- 27 events among participants randomized to the pooled retatrutide groups
- 23 events in the placebo group
Hazard Ratio:
1.12 (95% confidence interval 0.64 to 1.96)
Importantly, the confidence intervals for both analyses crossed 1.0.
These estimates are compatible with a range of possible effects and do not establish a cardiovascular benefit or increased risk. The study’s primary endpoint was weight change, and Lilly reported fewer events than anticipated. The separate TRIUMPH-Outcomes trial is designed to study cardiovascular and kidney events.
Safety and Side Effects
The overall safety profile observed in TRIUMPH-2 and TRIUMPH-3 was generally consistent with other incretin-based therapies.
The most commonly reported adverse events involved the gastrointestinal system, including:
- Nausea
- Diarrhea
- Vomiting
- Constipation
- Reduced appetite
Most gastrointestinal events were reported as mild to moderate in severity and occurred during dose escalation.
Researchers also reported:
- Dysesthesia (abnormal skin sensations)
- Urinary tract infections
In the published TRIUMPH-2 study, permanent discontinuation due to adverse events or death was reported in 4%, 12% and 8% of the 4 mg, 9 mg and 12 mg retatrutide groups, respectively, versus 5% with placebo. These figures describe that trial and its defined outcome; they do not establish comparative safety against other drugs.
Why Is Retatrutide Receiving So Much Attention?
Much of the interest surrounding retatrutide extends beyond weight reduction alone.
Across Phase 2 and Phase 3 research programs, investigators have observed changes in multiple metabolic measurements, including:
- Body weight
- Blood glucose regulation
- Liver fat
- Blood pressure
- Lipid profiles
- Inflammatory biomarkers
- Waist circumference
Because obesity, diabetes, cardiovascular disease, and metabolic dysfunction frequently overlap, therapies capable of affecting several interconnected metabolic pathways continue to receive significant research attention.
When Could Retatrutide Receive FDA Approval?
In July 2026, Lilly announced plans to submit a biologics application in the first quarter of 2027. After a court remand, FDA’s October 2 classification decision reaffirmed that retatrutide is not a biological product and stated that an application would follow the drug pathway. Classification is separate from approval, and the dispute may continue.
A regulatory submission is not the same as FDA approval.
Once submitted, the FDA will determine whether to accept the application for review before evaluating the complete clinical data package, manufacturing information, safety findings, and proposed labeling. The timing and outcome of that review remain uncertain.
Additional Research Programs
Retatrutide continues to be investigated across multiple clinical programs, including studies involving:
- Obesity
- Type 2 diabetes
- Obstructive sleep apnea
- Chronic low back pain
- Knee osteoarthritis pain
- Metabolic dysfunction-associated steatotic liver disease (MASLD)
- Kidney outcomes
- Cardiovascular outcomes
Additional data from these ongoing studies may provide further insight into the compound’s safety and efficacy across different patient populations.
What Do These Results Mean?
The latest TRIUMPH-2 and TRIUMPH-3 findings strengthen the growing body of evidence surrounding investigational retatrutide.
Why headline figures differ: Weight-change estimates can vary with the trial population, time point, dose and statistical estimand. A treatment-regimen analysis and an efficacy-estimand analysis are not interchangeable, and sponsor topline disclosures are not identical to full peer-reviewed reports. The evidence summarized here should also be kept separate from the regulatory milestones described in our retatrutide FDA approval-status guide.
Across multiple Phase 3 studies, researchers have consistently reported substantial average weight reductions along with improvements in measures of glucose regulation and several cardiometabolic risk markers.
Important questions remain. The cardiovascular analyses reported in TRIUMPH-3 were not sufficient to establish a statistically significant reduction in major cardiovascular events. The TRIUMPH-2 study has been published; the availability and details of other trial reports should be checked separately.
Additional analyses, future clinical studies and regulatory decisions will continue to shape understanding of retatrutide. A classification decision is not an approval or evidence that an application is under review.
Frequently Asked Questions
Is retatrutide FDA approved?
No. Retatrutide remains investigational and is not FDA approved.
How much weight did participants lose?
In TRIUMPH-3, Lilly reported an average body-weight reduction of 22.6%, or approximately 55.8 pounds, at 80 weeks in the highest studied group using its efficacy estimand. That estimate differs from an analysis that includes outcomes regardless of treatment discontinuation.
What is a triple agonist?
A triple agonist activates three hormone receptors simultaneously. Retatrutide targets the GLP-1 receptor, GIP receptor, and glucagon receptor.
Is retatrutide better than tirzepatide?
No completed head-to-head Phase 3 trial has established whether one therapy is superior to the other. Direct comparisons require appropriately designed clinical studies.
What were the most common side effects?
The most commonly reported adverse events were gastrointestinal and included nausea, diarrhea, constipation, vomiting, and decreased appetite.
When could retatrutide become available?
Lilly announced an early 2027 biologics filing plan in July 2026, but FDA’s October classification decision stated that an application would follow the drug pathway. No approval timeline has been confirmed.
References
- Eli Lilly and Company. Retatrutide Phase 3 TRIUMPH-2 and TRIUMPH-3 Topline Results. July 23, 2026.
- ClinicalTrials.gov Identifier: NCT05929079 (TRIUMPH-2)
- ClinicalTrials.gov Identifier: NCT05882045 (TRIUMPH-3)
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