Roche has announced positive topline results from CT-388-104, a phase 2 clinical trial evaluating enicepatide (CT-388), an investigational, once-weekly dual GLP-1/GIP receptor agonist, in adults living with Type 2 Diabetes (T2D) and overweight or obesity.

In the study, enicepatide met both primary endpoints, delivering dose-dependent and clinically meaningful reductions in blood glucose and body weight at 48 weeks. Patients receiving the highest titrated dose (24 mg) achieved an HbA1c reduction of 2.65 percent (from a baseline HbA1c of 8.1 percent).

Furthermore, 90 percent of patients in the 24 mg cohort reached an HbA1c level of ≤6.5 percent (diagnostic threshold for T2D) and 62 percent achieved normoglycemia (HbA1c < 5.7 percent), restoring blood glucose levels to a non-diabetic range. The mean weight loss at 48 weeks in the 24 mg enicepatide arm was 15.5 percent without a demonstrable plateau.

The safety and tolerability profile of enicepatide was consistent with other established incretin-based therapies, with the most common Adverse Events (AEs) being predominantly mild-to-moderate gastrointestinal effects. In addition, the treatment discontinuation rate due to adverse events was low (2 percent in enicepatide arms; 0 percent in placebo arm).

The totality of data positions enicepatide, a unique dually biased GLP-1/GIP receptor agonist, as a differentiated molecule designed for potentially greater efficacy with a favorable safety profile.

Levi Garraway, MD, PhD, Chief Medical Officer and Head of Global Product Development, Roche, said, “We are highly encouraged by the efficacy demonstrated by enicepatide in this phase 2 study, including the meaningful proportion of patients reaching normalised glucose levels within less than a year of treatment. 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 Type 2 Diabetes.”

Roche is advancing a broad late-stage development program for enicepatide, including 2 ongoing phase 3 studies in chronic weight management (ENITH-1 and ENITH-2) and plans to initiate a phase 3 glycemic-control program and cardiovascular outcomes trials in the first half of 2027.

Teresa Graham, Chief Executive Officer, Roche Pharmaceuticals, said, “These results reinforce our confidence in enicepatide and our ambition to rapidly advance its development for people living with obesity, diabetes, and cardiovascular disease. As we expand into late-stage clinical studies and explore novel combinations, we are leveraging our integrated diagnostic and therapeutic expertise to build a competitive cardiometabolic portfolio—aiming to protect people from early metabolic dysfunction to advanced organ damage, ultimately reducing the global disease burden.”