Roche Registers Phase 3 Trial Pitting Enicepatide Directly Against Tirzepatide in Type 2 Diabetes

Roche has registered a new Phase 3 trial that will test its investigational obesity and diabetes peptide enicepatide directly against the approved drug tirzepatide, according to a ClinicalTrials.gov record first posted on October 22, 2026. The study, internally named ENI-SPIRE-2 (NCT07889648), is sponsored by Hoffmann-La Roche with Chugai Pharmaceutical as a collaborator.

The trial is a randomized, open-label, active-controlled Phase 3 study that plans to enroll an estimated 948 adults with type 2 diabetes who have inadequate glycemic control despite treatment with oral glucose-lowering medications. Participants will be assigned to one of two arms, once-weekly tirzepatide as an active comparator or enicepatide, with the registry record listing a primary outcome of change in HbA1c (glycosylated hemoglobin) from baseline to week 72. Secondary outcomes include the percentage of participants reaching specific HbA1c thresholds, change in fasting glucose, percent change in body weight, and changes in blood pressure, lipids and other metabolic markers, tracked through week 72 with safety follow-up to week 75. As of the registry posting, the study is listed as not yet recruiting, with an estimated start date of December 1, 2026 and no sites yet posted.

Enicepatide, also known by the laboratory codes RO7795068 and CT-388, is a once-weekly, signaling-biased dual agonist of the GLP-1 and GIP receptors, the same combined mechanism used by tirzepatide. It was originally developed by Carmot Therapeutics, a company Roche acquired in December 2023. A phase 1, placebo-controlled trial of subcutaneous CT-388 in participants with overweight or obesity, published in the journal Molecular Metabolism in January 2026, reported mean body-weight change from baseline to day 29 of negative 4.7% to negative 8.0% across CT-388 dose groups, compared with negative 0.5% for placebo, with treatment-emergent adverse events described as mostly mild or moderate.

ENI-SPIRE-2 is not enicepatide's first Phase 3 trial. Two other Phase 3 studies, ENITH-1 (NCT07351045, estimated enrollment 2,000) in adults with obesity or overweight without type 2 diabetes, and ENITH-2 (NCT07351058, estimated enrollment 1,600) in adults with obesity or overweight and type 2 diabetes, were both first posted on ClinicalTrials.gov on January 20, 2026 and are listed as currently recruiting. Those two trials compare enicepatide against placebo. ENI-SPIRE-2 is the first enicepatide registry record to name tirzepatide, rather than placebo, as the active comparator.

Enicepatide is not approved by the FDA, the European Medicines Agency, Australia's Therapeutic Goods Administration or any other regulator for any indication, and no marketing application has been filed. The ClinicalTrials.gov record describes planned study design only; no efficacy or safety results comparing enicepatide with tirzepatide have been reported, and this article does not constitute treatment or dosing guidance.