Roche's Enicepatide Cuts HbA1c 2.65% and Weight 15.5% at 48 Weeks in Phase II Type 2 Diabetes Trial
核心洞察
Roche's once-weekly dual GLP-1 (搜索)/GIP (搜索) agonist enicepatide (搜索) met both primary endpoints in a 447-patient Phase II study in type 2 diabetes (搜索) with overweight or obesity (搜索).
At the 24 mg dose, HbA1c fell 2.65% from a baseline of 8.1% and mean body weight dropped 15.5% at 48 weeks with no plateau.
About 90% of patients reached HbA1c of 6.5% or lower and 62% achieved normoglycemia, while gastrointestinal side effects were mostly mild to moderate.
Roche reported top-line results from the Phase II CT-388-104 study of enicepatide (搜索) (CT-388), its investigational once-weekly subcutaneous dual GLP-1 (搜索)/GIP receptor (搜索) agonist, in adults with type 2 diabetes (搜索) and overweight or obesity (搜索). The drug met both primary endpoints at 48 weeks, producing dose-dependent reductions in HbA1c and body weight, according to the company.
The trial randomized 447 adults living with type 2 diabetes (搜索) mellitus and overweight or obesity (搜索) in a double-blind, placebo-controlled, parallel-group, multi-center design. Participants received once-weekly subcutaneous enicepatide (搜索) for 48 weeks, with dual primary outcomes defined as change from baseline in HbA1c and body weight at week 48.
Glycemic and Weight Outcomes at 24 mg
At the highest titrated dose of 24 mg, enicepatide (搜索) reduced HbA1c by 2.65% from a baseline of 8.1%. Approximately 90% of patients achieved an HbA1c of 6.5% or lower, and 62% reached normoglycemia, defined as HbA1c below 5.7%. In the subgroup with poor baseline glycemic control (HbA1c above 8.5%), the 24 mg dose produced an HbA1c reduction of 4.13% at 48 weeks.
Mean body weight fell 15.5% at 48 weeks at the 24 mg dose, and the weight trajectory showed no evidence of a plateau.
Levi Garraway, Roche's Chief Medical Officer and Head of Global Product Development, said the efficacy demonstrated in the Phase II study was encouraging, including the substantial proportion of patients achieving normalized blood sugar in under a year of treatment. He said that combined with sustained weight loss, the drug has the potential to become a best-in-class therapy for type 2 diabetes (搜索), capable of reducing and preventing complications while improving patients' metabolic health.
Tolerability and Discontinuations
Enicepatide (搜索) was generally well tolerated. Adverse events consisted primarily of mild-to-moderate gastrointestinal reactions. Discontinuations due to adverse events were 2.0% in the enicepatide groups versus 0% for placebo.
Mechanism and Development Program
Enicepatide (搜索) is a dual-biased GLP-1 (搜索)/GIP receptor (搜索) agonist administered once weekly by subcutaneous injection, in development for obesity (搜索), type 2 diabetes (搜索) and additional cardiovascular indications. Its mechanism activates both the GLP-1 and GIP (搜索) hormones involved in metabolic regulation, similar to Eli Lilly's Zepbound. Roche states that the dual GLP-1/GIP mechanism and biased signaling approach could potentially differentiate enicepatide from existing treatments.
Roche is advancing a broad late-stage program for enicepatide (搜索), with two ongoing Phase III studies in chronic weight management, ENITH-1 and ENITH-2. The company plans to initiate a Phase III glycemic-control program and cardiovascular outcomes trials in the first half of 2027, while also testing higher doses and exploring combinations with other weight-loss drugs.
Origin of the Asset
Enicepatide (搜索) was formerly known as CT-388 and was originally developed by Carmot Therapeutics (搜索). Roche acquired the company in 2023 for $3.1 billion, securing development rights to the drug. The Phase II data reported this week further validate the strategic value of that acquisition as Roche builds its position in the weight-loss and metabolic space.
Competitive Context
Roche is entering a global obesity (搜索) drug market that was valued at approximately $45.1 billion in 2026 and is expected to grow to $150 billion by 2035. In the United States, more than two in five adults are classified as obese, and roughly one in every 11 adults is severely obese. The incretin market already includes established therapies from Eli Lilly and Novo Nordisk.
Roche notes that the eventual commercial opportunity for enicepatide (搜索) will depend on Phase III efficacy and safety results, differentiation from competing incretin therapies, and the company's ability to establish a competitive position in the obesity (搜索) market. Whether the Phase II efficacy can be replicated in larger Phase III trials will be the key determinant of its ability to compete head-to-head with Eli Lilly and Novo Nordisk.