Roche's (OTCQX: RHHBY) enicepatide, a once-weekly dual GLP-1/GIP receptor agonist, produced substantial reductions in both blood glucose and body weight in a Phase II trial in adults with type 2 diabetes (T2D) and overweight or obesity, adding glycemic data to a weight-loss profile that has already drawn comparisons to tirzepatide. Roche said it plans to initiate a Phase III glycemic-control program and cardiovascular outcomes trials in the first half of 2027.
The CT-388-104 study was a randomized, double-blind, placebo-controlled Phase II trial enrolling 447 adults with T2D and overweight or obesity, evaluating once-weekly subcutaneous enicepatide over 48 weeks. The trial carried dual primary endpoints of change from baseline in HbA1c and body weight at week 48, both of which were met, Roche reported.
Enicepatide, previously known as CT-388, was developed by Carmot Therapeutics and entered Roche’s pipeline through its January 2024 acquisition of the company, agreed at USD 2.7 billion upfront plus up to USD 400 million in milestones. The molecule activates both the GLP-1 and GIP receptors with minimal β-arrestin recruitment on either receptor, a biased signaling design intended to reduce receptor internalization and extend pharmacological activity relative to conventional incretin agonists.
For the 24mg dosage, mean HbA1c fell by 2.65 percentage points from a baseline of 8.1%, with 90% of patients on that 24mg dose reaching the T2D diagnostic threshold of ≤6.5% HbA1c and 62% achieving normoglycemia (HbA1c <5.7%). In the subgroup with poor baseline control (HbA1c >8.5%), the mean reduction was 4.13 percentage points. Mean weight loss at 48 weeks was 15.5%, with no plateau observed. The discontinuation rate due to adverse events was 2.0% in enicepatide arms versus 0.0% in the placebo arm, with gastrointestinal effects the most common adverse events, consistent with the incretin class.