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, which runs alongside the separate 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, the same day they were presented at the American Diabetes Association (ADA) 2026 Scientific Sessions in New Orleans. In 537 adults with type 2 diabetes not controlled by diet and exercise alone, retatrutide lowered HbA1c by up to 1.94 percentage points and body weight by up to 15.3% at 12 mg over 40 weeks. That is blood sugar control on par with tirzepatide with much greater weight loss, a clinically meaningful difference given how hard weight loss is for people with type 2 diabetes.

The peer-reviewed Lancet paper also refined the press-release numbers. The final per-dose figures below are 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 at 24 weeks (the primary endpoint)
• 53-86% of participants on 4 mg or more reached HbA1c of 7.0% or less at 24 weeks, versus 22% on placebo
• Weight loss of up to -16.9% at 12 mg at 36 weeks
• The active comparator, dulaglutide 1.5 mg, lowered HbA1c by 1.41 points at 24 weeks

Study Design

Population

Adults aged 18 or older with:

• Type 2 diabetes inadequately controlled with diet and exercise alone (no background glucose-lowering drug)
• HbA1c 7.0-9.5%
• BMI ≥23 kg/m²

Treatment Arms

Randomized 1:1:1:1, double-blind, placebo-controlled (no active comparator):

• Retatrutide 4 mg (with dose escalation)
• Retatrutide 9 mg (with dose escalation)
• Retatrutide 12 mg (with dose escalation)
• Placebo

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 (Bajaj et al., “Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise”) 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%.

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 grew with dose up to 12 mg. The highest dose gave both the largest blood sugar improvement (-1.94 points) and the most 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 retatrutide’s glucagon-receptor component.
• Gastrointestinal adverse events (nausea, diarrhea) were mostly mild to moderate, as expected for the incretin class.
• Two deaths occurred in the 4 mg group; both were adjudicated as unrelated to the study drug.
• Dysesthesia rates were much lower than in the obesity trials (12.5% at 12 mg in TRIUMPH-1, 20.9% in TRIUMPH-4), likely because of the shorter 40-week duration and the type 2 diabetes population.

Significance

TRANSCEND-T2D-1 is the anchor trial for a type 2 diabetes indication, just as TRIUMPH-1 (reported May 21, 2026) anchors the obesity indication. Together with TRIUMPH-2, -3 and -4, these readouts give Eli Lilly the core efficacy package for its regulatory filing (Lilly plans to file no later than the first quarter of 2027; in July 2026 it named obesity, knee osteoarthritis pain and obstructive sleep apnea as the uses its data support, and it has not said when it will seek a type 2 diabetes indication). The FDA ruled on October 2, 2026 that retatrutide is a drug, so the application must be a New Drug Application (NDA); Lilly disputes the FDA ruling in court and has not said which pathway it will use. Approval for type 2 diabetes as well would widen the group of patients who could use retatrutide, since adults with T2D make up a large share of people now taking tirzepatide and semaglutide. The head-to-head trial against semaglutide 2 mg, TRANSCEND-T2D-2, reported topline results on October 28, 2026 (A1C -2.2 points on both retatrutide doses vs -1.8; not yet peer reviewed), and TRANSCEND-T2D-3 is still running; the obesity-with-T2D trial TRIUMPH-2 reported on July 23, 2026 (-20.8% weight loss and A1C -1.5 points at 12 mg over 80 weeks).