Retatrutide — Research Dossier

The Phase 2 evidence

The pivotal Phase 2 obesity trial (Jastreboff et al., New England Journal of Medicine, 2023) was a randomised, double-blind, placebo-controlled, dose-ranging study conducted across 14 US sites. It enrolled 338 adults with obesity (BMI ≥30 kg/m², or ≥27 kg/m² with at least one weight-related complication) without type 2 diabetes.

Participants received once-weekly subcutaneous retatrutide at doses of 1 mg, 4 mg, 8 mg, or 12 mg, or placebo, over 48 weeks. The primary endpoint was percentage change in body weight from baseline.

Results at 48 weeks (mean change in body weight)

• Retatrutide 1 mg: −8.7%
• Retatrutide 4 mg: −17.1%
• Retatrutide 8 mg: −17.5%
• Retatrutide 12 mg: −24.2% (placebo-adjusted approximately −22.0%)
• Placebo: −2.1%

All active dose groups were statistically significant versus placebo (p<0.001). A clear dose-response was observed across the 1–12 mg range. Notably, the weight-loss curve at the highest dose had not plateaued by week 48, suggesting the full magnitude of effect was not captured within the trial window.

Phase 2a liver disease substudy (Nature Medicine, 2024)

A separate Phase 2a randomised trial published in Nature Medicine (2024) evaluated retatrutide in adults with metabolic dysfunction-associated steatotic liver disease (MASLD). At higher doses, the trial reported relative liver-fat reductions exceeding 80%, with most high-dose participants reaching normal liver-fat levels at 24 weeks. This finding is significant because hepatic steatosis is a common comorbidity of obesity and one not consistently addressed by GLP-1 mono-agonists.

The liver substudy is reported separately from the main obesity programme. Its patient population, trial duration, and endpoints differ from the TRIUMPH Phase 3 trials; results cannot be directly extrapolated across programmes.

The Phase 3 programme: TRIUMPH

Eli Lilly initiated the TRIUMPH programme to support regulatory submissions for retatrutide across multiple patient populations. Total enrolment across the weight management and type 2 diabetes arms exceeds 5,800 participants.

TRIUMPH-4 — topline results reported December 2025

TRIUMPH-4 enrolled adults with obesity and knee osteoarthritis without type 2 diabetes. Topline results reported December 2025 showed approximately 28.7% mean weight reduction at 68 weeks at the highest dose, alongside reported improvements in osteoarthritis pain measures. Discontinuations were noted to correlate with baseline BMI.

TRIUMPH-1 — topline results reported May 2026 (NCT05929066)

The pivotal obesity trial (adults with obesity without type 2 diabetes, approximately 2,500 participants) reported topline results in May 2026. At the highest dose, mean weight reduction was approximately 28.3% at 80 weeks, rising to approximately 30.3% in a pre-specified extension to 104 weeks.

Further readouts pending

• TRIUMPH-2 (NCT05929365): Adults with obesity and type 2 diabetes (approximately 1,100 participants). Topline timing not confirmed at time of writing.
• TRIUMPH-3: Cardiovascular outcomes in a high-risk population. Details and timeline not yet publicly disclosed.

Safety signals reported

Across Phase 2 and the Phase 3 topline disclosures to date, gastrointestinal adverse events — nausea, vomiting, constipation, and diarrhoea — have been the most commonly reported effects. This is consistent with the GLP-1 receptor agonist class profile.

Adverse events were predominantly mild to moderate in severity and concentrated during the dose-escalation phase. TRIUMPH-4 noted that discontinuations correlated with baseline BMI, suggesting participants with higher baseline BMI were more likely to discontinue, potentially due to more pronounced GI effects during escalation.

No novel safety signals beyond the established GLP-1 receptor agonist class profile have been reported in the published Phase 2 data or topline Phase 3 disclosures. Full safety data from Phase 3 peer-reviewed publications remain pending.

Regulatory status

As of June 2026, retatrutide has not been approved by the FDA, EMA, MHRA, or any other regulatory authority. No marketing authorisation exists in any jurisdiction. The compound is legally available only to participants enrolled in its clinical trials.

Eli Lilly has not announced a New Drug Application (NDA) or Biologics License Application (BLA) submission date. Regulatory submission typically follows compilation and review of the full Phase 3 dataset, including peer-reviewed publications from TRIUMPH-1, TRIUMPH-2, and subsequent readouts.

Nexyra Lab supplies research-grade retatrutide strictly for in vitro laboratory use. It is not a licensed medicinal product and is not subject to the regulatory oversight applicable to pharmaceutical-grade retatrutide administered in the TRIUMPH trials.