Enicepatide Meets Primary End Points in Phase 2 Trial of Adults With Type 2 Diabetes, Obesity

Enicepatide (CT-388; Roche, Genentech), a once-weekly dual glucagon-like peptide-1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, met both primary end points in the phase 2 CT-388-104 clinical trial (NCT06628362), according to a news release from Roche. The trial, which enrolled adult patients with type 2 diabetes (T2D) and overweight or obesity, demonstrated that the investigational agent produced dose-dependent reductions in blood glucose and body weight at 48 weeks.^1,2

CT-388-104’s Study Design

CT-388-104 is a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial that evaluated once-weekly subcutaneous enicepatide for 48 weeks in 447 adults with T2D and overweight or obesity, with dual primary end points of change from baseline in hemoglobin A_1C (HbA_1C) and body weight at week 48. The dose-finding study includes a placebo arm and 4 enicepatide dose levels. Eligible participants were aged 18 to 75 years with a BMI of 25.0 kg/m² or greater.^1,2

Patients receiving the highest titrated dose (24 mg) achieved an HbA1_C reduction of approximately 2.65% from a baseline of 8.1%. In that cohort, 90% of patients reached an HbA_1C of 6.5% or lower, and 62% achieved normoglycemia (HbA_1C < 5.7%). Among patients with poor baseline glycemic control (HbA_1C > 8.5%), enicepatide 24 mg lowered HbA_1C by 4.13%.¹

Mean weight loss in the 24-mg arm was approximately 15.5% at 48 weeks, with no demonstrable plateau. The announcement did not report placebo-adjusted results or outcomes for the lower-dose arms.¹

The safety profile was consistent with established incretin-based therapies. The most common adverse events (AEs) were predominantly mild-to-moderate gastrointestinal effects. Discontinuation due to AEs occurred in only 2.0% of patients across the enicepatide arms compared with 0.0% in the placebo arm. There were no new safety signals identified.¹

What is Enicepatide?

Enicepatide belongs to the incretin-based therapy class, which mimics hormones released by the gut after eating. It is a synthetic, single-molecule peptide that activates both the GLP-1 and GIP receptors while favoring cyclic adenosine monophosphate (cAMP) signaling over β-arrestin recruitment at each. Preclinical studies suggest that cAMP-biased signaling reduces GLP-1 receptor internalization and prolongs drug effects, which may improve efficacy over unbiased agents. In cell-based assays, enicepatide did not recruit β-arrestin-2 to the human GLP-1 receptor and caused substantially less receptor internalization than native GLP-1.³

Phase 1 trial (NCT04838405) data published in Molecular Metabolism show that enicepatide's mean half-life ranged from roughly 123 to 151 hours, supporting once-weekly dosing. Participants with overweight or obesity without diabetes lost approximately 4.7% to 8.0% of body weight after 4 weeks, compared with 0.5% with placebo.⁴

Diabetes affects nearly 600 million adults worldwide, with T2D accounting for approximately 90% of cases. People with obesity are 7 times more likely to develop T2D than those with a normal body mass index, and people with diabetes face a 2- to 4-fold higher risk of hypertension, heart failure, stroke, and coronary artery disease.¹

Currently, Roche has 2 ongoing phase 3 trials in chronic weight management, ENITH-1 (NCT07351045) and ENITH-2 (NCT07351058), and plans to initiate a phase 3 glycemic control program and cardiovascular outcomes trials in the first half of 2027. Enicepatide is not yet approved by the FDA for any indication.¹

“We are highly encouraged by the efficacy demonstrated by enicepatide in this phase 2 study, including the meaningful proportion of patients reaching normalized glucose levels within less than a year of treatment,” Levi Garraway, MD, PhD, Roche’s chief medical officer and head of global product development. “Combined with sustained weight loss, enicepatide offers a potential best-in-disease profile capable of reducing and preventing complications as well as enhancing metabolic health for people living with T2D.”¹

REFERENCES

1. Roche announces positive phase II results for dual GLP-1/GIP receptor agonist enicepatide in people living with type 2 diabetes and overweight or obesity. News release. Roche. September 22, 2026. Accessed September 22, 2026. https://www.roche.com/media/releases/med-cor-2026-09-22

2. A study of enicepatide (CT-388) in participants who are overweight or obese with type 2 diabetes mellitus. ClinicalTrials.gov identifier: NCT06628362. Updated June 2026. Accessed September 22, 2026. https://clinicaltrials.gov/study/NCT06628362

3. GLP-1 agonists. Cleveland Clinic. Updated July 3, 2023. Accessed September 22, 2026. https://my.clevelandclinic.org/health/treatments/13901-glp-1-agonists

4. Chakravarthy MV, Rodriguez R, Hergarden A, et al. Effects of CT-388, a once-weekly signaling-biased dual GLP-1/GIP receptor agonist, on weight loss and glycemic control in preclinical models and participants with obesity. Mol Metab. 2026;103:102291.doi: 10.1016/j.molmet.2025.102291