TRANSCEND-T2D-1: Phase 3 Type 2 Diabetes Trial (Results-Published)

Study Overview

TRANSCEND-T2D-1 is the first Phase 3 trial in Eli Lilly’s TRANSCEND program (Triple Receptor Agonist for Normalization of Sustained Cardiometabolic Endpoints in Diabetes), separate from but parallel to the TRIUMPH obesity program. Positive topline results were announced on March 19, 2026 via Eli Lilly press release and subsequently elaborated at the Q1 2026 earnings call on April 30, 2026. Across all doses tested, retatrutide produced HbA1c reductions of 1.7-2.0 percentage points and weight loss of 11.5-16.8% over 40 weeks (n=537) — glycemic control on par with tirzepatide while delivering additional weight loss, a clinically meaningful distinction given the difficulty people with type 2 diabetes face losing weight.

Building on Phase 2 Diabetes Data

The Phase 2 type 2 diabetes trial (NCT04867785) demonstrated:

• HbA1c reduction of up to -2.02% at 12 mg/36 weeks
• 71% of participants achieved HbA1c <7% at the highest dose
• Significant weight loss (-16.9% at 12 mg) concurrent with glycemic improvement
• Active comparator (dulaglutide 1.5 mg) achieved only -1.4% HbA1c reduction

Study Design

Population

Adults aged 18-75 with:

• Type 2 diabetes (HbA1c 7.0-10.5%)
• Currently on metformin monotherapy (stable dose for at least 3 months)
• BMI ≥25 kg/m²

Treatment Arms

• Retatrutide 9 mg (with dose escalation)
• Retatrutide 12 mg (with dose escalation)
• Placebo
• Active comparator (likely semaglutide 1.0 mg or tirzepatide)

Endpoints

Primary endpoints:

• Change in HbA1c from baseline at 40 weeks
• Proportion achieving HbA1c <7%

Key secondary endpoints:

• Proportion achieving HbA1c <6.5% and <5.7%
• Body weight change
• Fasting plasma glucose change
• Time in glucose range (CGM substudy)
• Composite metabolic endpoint (HbA1c + weight + blood pressure)

Topline Results (Announced March 19, 2026)

Eli Lilly announced positive topline results via press release on March 19, 2026. Full data are expected to be presented at the American Diabetes Association (ADA) 2026 Scientific Sessions (June 5-8, New Orleans), with peer-reviewed publication to follow.

Notably, the dysesthesia rate of 2.3-4.5% across retatrutide doses in TRANSCEND-T2D-1 is substantially lower than the 12.5% reported in TRIUMPH-1 and 20.9% in TRIUMPH-4 at 12 mg — likely reflecting both the shorter trial duration (40 weeks vs 68-80 weeks) and the type 2 diabetes population. Discontinuation rates were also notably lower than in the obesity trials. The slightly higher HbA1c reduction at 9 mg than at 12 mg suggests a plateau in glycemic response, while weight loss continues to increase dose-dependently.

Significance

TRANSCEND-T2D-1 is the regulatory-anchoring trial for retatrutide’s type 2 diabetes indication, separate from the obesity-anchor TRIUMPH-1 (reported May 21, 2026). Together, these two readouts give Eli Lilly the core efficacy package for an NDA filing covering both indications. Approval for both significantly broadens retatrutide’s potential patient population — adults with T2D currently represent a substantial fraction of those receiving tirzepatide and semaglutide. Additional T2D trials (TRANSCEND-T2D-2 head-to-head vs semaglutide) and the obesity-with-T2D trial TRIUMPH-2 will round out the diabetes program.