Roche reported positive topline results from its Phase II clinical trial, CT388-103, evaluating CT-388, Roche’s investigational dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist being developed for the treatment of obesity.

The phase II study demonstrated that once-weekly subcutaneous dosing of CT-388 can lead to substantial placebo-adjusted weight loss at 48 weeks, with participants continuing to lose weight without reaching a plateau.¹

CT-388 is an investigational once-weekly injectable therapy designed to reduce appetite and regulate blood glucose by selectively activating both GLP-1 and GIP receptors involved in energy homeostasis.¹ The molecule was engineered to provide potent receptor activation with minimal ß-arrestin recruitment, a signaling profile intended to reduce receptor internalization and desensitization, which may support prolonged pharmacological activity.

In the trial, CT-388 was administered in doses up to 24 mg, achieving a placebo-adjusted mean weight reduction of 22.5% at week 48 using the efficacy estimand.¹ For the treatment-regimen estimand, the corresponding placebo-adjusted weight loss was 18.3%, with a reported p-value of less than 0.001. The results also showed a clear dose-response relationship, supporting the consistency of weight loss outcomes across increasing dose levels.

At 24 mg, the majority of participants achieved clinically meaningful weight loss thresholds, and by week 48, 95.7% of individuals treated with CT-388 lost a minimum of 5% of body weight, while 87% achieved reductions of at least 10%.¹

Nearly half of the study participants lost 20% or more of their body weight, while 26.1% reached weight loss of 30% or greater. Among participants who were pre-diabetic at baseline, 73% achieved normal blood glucose levels at week 48, compared with 7.5% in the placebo group.¹

What was CT388-103?

CT388-103 was a multi-center, randomized, double-blind, placebo-controlled, parallel-group, dose-finding Phase II study conducted in 469 adults with obesity or who are overweight and have at least one weight-related comorbidity, excluding type 2 diabetes. Study participants were assigned to low, middle, or high doses of CT-388 or assigned to receive placebo across five dosing cohorts with different up-titration schemes. The safety and tolerability profile of CT-388 remained consistent with expectations for the incretin class.

“We are pleased to see such meaningful weight loss in people treated with CT-388,” said Levi Garraway, M.D., Ph.D., Roche’s chief medical officer and head of global product development. “The robust weight loss combined with a well-tolerated safety profile reinforces our confidence in the clinical development program as we advance to Phase III trials.”

What were the key findings from the CT388-103 Phase II trial?

CT-388 met its primary endpoint by demonstrating significant percent reductions in body weight from baseline through 48 weeks when compared with placebo.¹ Participants who were administered with the highest dose continued to lose weight throughout the study period with no evidence of a plateau. The trial also showed that a significant proportion of participants reached higher weight-loss thresholds of 20% and 30%, outcomes that remain difficult to achieve with currently available therapies. Results showed improvements in glycemic status among pre-diabetic participants, further suggest potential metabolic benefits beyond weight reduction.¹

CT-388 is currently being evaluated in an additional Phase II study, CT388-104, designed to assess its efficacy, safety, and tolerability in participants living with obesity or overweight who also have type 2 diabetes.¹

Roche has indicated that the Phase III clinical program for CT-388 in obesity, Enith1 and Enith2, is expected to begin in the first quarter of 2026.¹

Sources

1. Roche announces positive Phase II results for its dual GLP-1/GIP receptor agonist CT-388 in people living with obesity. Roche. January 26, 2026. https://www.roche.com/media/releases/med-cor-2026-01-27