Roche's dual GLP-1/GIP drug posts strong phase 2 diabetes results

Overview

Updated Sep 22

Roche's experimental once-weekly diabetes injectable cut blood sugar and body weight in a 48-week phase 2 trial announced September 22. Patients on the highest 24 mg dose saw HbA1c drop 2.65 percentage points and weight fall 15.5%.

Enicepatide is a dual GLP-1/GIP receptor agonist, the same mechanism as Eli Lilly's tirzepatide. Ninety percent of the top-dose cohort reached HbA1c of 6.5% or below, the diagnostic threshold for diabetes. Roche plans phase 3 diabetes and cardiovascular trials in the first half of 2027.

Why it matters

If enicepatide's phase 3 data holds, the $150 billion obesity market gains a third player and six in ten diabetes patients may reach normal blood sugar.

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Key Indicators

2.65 points

HbA1c reduction at 24 mg

Mean reduction from an 8.1% baseline at 48 weeks in people with type 2 diabetes.

15.5%

Mean weight loss at 48 weeks

No plateau reached by study end in the 24 mg arm.

90%

Patients at HbA1c of 6.5% or below

Share of the 24 mg cohort meeting the type 2 diabetes diagnostic threshold.

62%

Patients with normoglycemia

Share of the 24 mg cohort with HbA1c below 5.7%, a non-diabetic range.

4.13 points

HbA1c reduction in poorly controlled patients

Patients with baseline HbA1c above 8.5% on the 24 mg dose.

2.0%

Discontinuation rate from side effects

Across enicepatide arms, versus 0% on placebo.

Voices

Curated perspectives — historical figures and your fellow readers.

People Involved

Teresa Graham

Head of Roche Pharmaceuticals

Overseeing enicepatide's phase 3 program

Organizations Involved

Roche / Genentech

Pharmaceutical and diagnostics company

Running phase 3 obesity trials, planning phase 3 diabetes trials

Swiss drugmaker developing enicepatide, a dual GLP-1/GIP agonist for diabetes and obesity.

Eli Lilly and Company

Pharmaceutical company

Competitor; markets tirzepatide as Mounjaro and Zepbound

Makes tirzepatide, the top-selling dual GLP-1/GIP agonist sold as Mounjaro for diabetes and Zepbound for obesity.

Novo Nordisk

Pharmaceutical company

Competitor; markets semaglutide as Ozempic and Wegovy

Makes semaglutide, the top-selling GLP-1 agonist sold as Ozempic for diabetes and Wegovy for obesity.

Carmot Therapeutics

Biotechnology company (acquired)

Acquired by Roche in early 2024

Developed CT-388, the molecule now called enicepatide.

Timeline

December 2023 September 2026

3 events Latest: September 22nd, 2026 · 2 months ago

September 2026
Phase 2 diabetes trial succeeds
Latest Clinical Trial

CT-388-104 hit both endpoints: 2.65-point HbA1c cut and 15.5% weight loss at 48 weeks.
September 22nd, 2026
January 2026
Phase 2 obesity trial hits its endpoints
Clinical Trial

CT388-103 showed 22.5% placebo-adjusted weight loss at 48 weeks in people with obesity.
January 27th, 2026
December 2023
Roche agrees to buy Carmot Therapeutics
Deal

Roche announced a $2.7 billion upfront acquisition of Carmot, gaining the dual agonist CT-388.
December 4th, 2023

Scenarios

Enicepatide clears phase 3 at full dose, rivaling Lilly's tirzepatide

Likely Resolves by Jul 31, 2027

Discussed by: Goldman Sachs analysts led by James Quigley

Roche launches phase 3 diabetes trials in the first half of 2027 at the 24 mg dose. The 2.0% discontinuation rate in phase 2 suggests patients tolerate the top dose, so the 2.65-point HbA1c reduction could survive the larger study. Success would position enicepatide as the efficacy leader in the dual GLP-1/GIP class.

Tolerability caps enicepatide below 24 mg

Possible Resolves by Jul 31, 2027

Discussed by: Clinical Trial Vanguard, noting dropout rates at upper doses often soften efficacy stories

Longer exposure in phase 3 pushes discontinuation rates up at 24 mg, prompting Roche to cap doses below the peak. Those caps would pull efficacy toward class averages, since the phase 2 headline numbers came from the top dose.

Petrelintide combination becomes Roche's differentiator

Possible Resolves by Q2 2028

Discussed by: Roche R&D leadership at the American Diabetes Association meeting, June 2026

A phase 2 trial combining enicepatide with the amylin agonist petrelintide, planned for 2026, shows better tolerability or efficacy than enicepatide alone. Roche would then position the combination, not monotherapy, as its answer to Lilly and Novo.

Historical Context

3 moments from history that rhyme with this story — and how they unfolded.

2018-2023

Tirzepatide's rise (2018-2023)

Eli Lilly advanced tirzepatide, the first dual GLP-1/GIP agonist, through phase 3 trials covering diabetes and obesity. In people without diabetes, average weight loss reached 16% to 22.5%.

Then

Tirzepatide won FDA approval as Mounjaro for diabetes in 2022 and Zepbound for obesity in 2023, becoming a blockbuster within a year.

Now

Set the efficacy benchmark every subsequent dual agonist must beat.

Why this matters now

Enicepatide uses the same two-receptor mechanism with a different receptor-binding profile, aimed specifically at exceeding tirzepatide's numbers.

2017-2024

Semaglutide's cardiovascular expansion (2017-2024)

Novo Nordisk's semaglutide moved from diabetes into obesity, then its SELECT trial showed cardiovascular benefits in overweight patients without diabetes.

Then

Expanded the GLP-1 market beyond glucose control to heart-disease prevention, driving worldwide demand.

Now

Made cardiovascular-outcome data a standard requirement for next-generation metabolic drugs.

Why this matters now

Roche plans a cardiovascular-outcomes study for enicepatide, matching the standard semaglutide set.

2005-2010

Exenatide, the first GLP-1 (2005)

Byetta (exenatide) became the first approved GLP-1 receptor agonist for type 2 diabetes. It required twice-daily injections and produced modest blood-sugar reductions with frequent nausea.

Then

Opened the incretin class with real tolerability limits that capped adoption.

Now

Spurred two decades of formulation and mechanism advances leading to once-weekly and dual-receptor drugs.

Why this matters now

The class has moved from modest single-digit HbA1c reductions to 2.65-point cuts and 15.5% weight loss.