Phase 2 Trial: The Landmark Results
The pivotal Phase 2 trial for retatrutide was a randomized, double-blind, placebo-controlled study conducted across multiple sites. Results were published in The New England Journal of Medicine in 2023, generating significant attention in the medical community for the magnitude of weight loss observed.
Trial Design
Participants were adults with a BMI of 30 or higher, or 27 or higher with at least one weight-related condition (such as hypertension or dyslipidemia), but without type 2 diabetes. They were randomized to one of four active dose groups or placebo, with doses gradually escalated over the first several weeks to improve tolerability.
Weight Loss Results by Dose
| Dose Group | Avg. Weight Change at 24 Weeks | Avg. Weight Change at 48 Weeks |
|---|---|---|
| Placebo | −2.1% | −2.1% |
| 1 mg weekly | −7.9% | −8.7% |
| 4 mg weekly | −15.5% | −17.3% |
| 8 mg weekly | −17.3% | −22.8% |
| 12 mg weekly | −19.9% | −24.2% |
Notable finding: Weight loss curves had not plateaued at 48 weeks in the higher dose groups, suggesting even greater reductions may be achievable with longer treatment duration — a finding that strongly influenced the design of the Phase 3 program.
Secondary Outcomes
Beyond weight loss, the Phase 2 trial captured several important metabolic endpoints. Participants showed meaningful improvements in waist circumference, blood pressure, fasting insulin levels, and lipid profiles. These cardiometabolic benefits are consistent with — and in several measures exceeded — those seen in comparable trials of semaglutide and tirzepatide.
Phase 2 Diabetes Trial
A separate Phase 2 trial evaluated retatrutide specifically in patients with type 2 diabetes. This population is distinct because blood glucose control is an additional primary endpoint alongside weight reduction.
Results showed significant reductions in HbA1c (a key marker of long-term blood sugar control) across all dose groups, with the highest doses producing HbA1c reductions comparable to the best-in-class approved diabetes medications. Hypoglycemia rates were low, consistent with the glucose-dependent mechanism of GLP-1 and GIP agonism.
Phase 3: The TRIUMPH Program
Building on the Phase 2 results, Eli Lilly launched a comprehensive Phase 3 development program. Phase 3 trials involve thousands of participants across multiple countries and are designed to confirm efficacy, characterize long-term safety, and support regulatory submissions.
TRIUMPH-1 — Obesity (Non-Diabetic)
The flagship Phase 3 trial in adults with obesity without type 2 diabetes. Primary endpoint is percentage change in body weight at 72 weeks. This trial will form the basis of the primary NDA submission for an obesity indication.
TRIUMPH-2 — Type 2 Diabetes
Phase 3 evaluation in patients with type 2 diabetes, measuring both glycemic control (HbA1c) and body weight reduction as co-primary endpoints.
TRIUMPH-3 — Cardiovascular Outcomes
A dedicated cardiovascular outcomes trial (CVOT) required by the FDA for drugs in this class. This large, long-duration trial will assess whether retatrutide reduces the risk of major adverse cardiovascular events (MACE) in high-risk patients.
TRIUMPH-4 — MASH/Liver Disease
Investigating retatrutide's potential in metabolic-associated steatohepatitis (MASH, formerly NAFLD). The glucagon receptor component is thought to directly reduce liver fat accumulation, making this a potentially differentiated indication.
How to Enroll in a Trial
If you are interested in participating in a retatrutide clinical trial, the primary resource is ClinicalTrials.gov, the official US government registry of clinical studies. Search for "retatrutide" or "LY3437943" to find currently enrolling studies.
General eligibility requirements for the obesity trials typically include:
Adults aged 18 or older with a BMI of 30+, or 27+ with a weight-related health condition. Exclusion criteria usually include prior bariatric surgery, certain cardiovascular conditions, pregnancy, and use of other weight loss medications. Each trial has specific criteria — review them carefully and speak with your doctor before applying.