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

Property	Value
Trial Name	TRANSCEND-T2D-1
Phase	3
Status	results-published
Enrollment	537 participants
Start Date	January 1, 2024
Conditions	type 2 diabetes
Primary Endpoints	Change in HbA1c from baseline at 40 weeks; Proportion of participants achieving HbA1c below 7%

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. Topline results were first announced on March 19, 2026, and the full results were published in The Lancet on June 6, 2026 — simultaneously presented at the American Diabetes Association (ADA) 2026 Scientific Sessions in New Orleans. In 537 adults with type 2 diabetes on metformin, retatrutide produced HbA1c reductions up to 1.94 percentage points and weight loss up to 15.3% at 12 mg over 40 weeks — glycemic control on par with tirzepatide while delivering substantially greater weight loss, a clinically meaningful distinction given how difficult weight loss is for people with type 2 diabetes.

The move from press-release topline to peer-reviewed Lancet publication also sharpened the numbers: the final per-dose figures below reflect the published data and differ slightly from the early topline estimates.

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)

Results (Published in The Lancet, June 6, 2026)

The full trial was published in The Lancet (“Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes”) and presented at ADA 2026. The trial enrolled 537 adults across 48 sites in the United States, Mexico, and India, with a mean baseline HbA1c of 7.9%.

Metric	Placebo	4 mg	9 mg	12 mg
HbA1c change (from 7.9%)	-0.81%	-1.69%	-1.86%	-1.94%
Weight change	-2.6%	-11.5%	-13.9%	-15.3%

Glycemic target achievement: 82-89% of participants across the retatrutide doses reached HbA1c below 7.0% (the standard treatment target), and 75-83% reached the tighter ≤6.5% threshold.

Both HbA1c reduction and weight loss increased dose-dependently through 12 mg — the highest dose delivered both the greatest glycemic improvement (-1.94 points) and the greatest weight loss (-15.3%). (Note: earlier press-release estimates had shown a slight HbA1c plateau at 9 mg; the peer-reviewed data instead show a clean dose-response.)

Safety

No severe hypoglycemia was reported in any arm — an important finding given the glucagon-receptor component of retatrutide.
Gastrointestinal adverse events (nausea, diarrhea) were predominantly mild to moderate, consistent with the incretin class.
Two deaths occurred in the 4 mg group; both were adjudicated as unrelated to the study drug.
Dysesthesia rates were substantially lower than in the obesity trials (12.5% at 12 mg in TRIUMPH-1, 20.9% in TRIUMPH-4), likely reflecting the shorter 40-week duration and the type 2 diabetes population.

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.