Roche’s enicepatide cut HbA1c by 2.65% and body weight by 15.5% at 48 weeks in a Phase II type 2 diabetes trial.
Written By: Anamika Koshti, PharmD
Reviewed By: Pharmacally Editorial Team
Roche reported positive topline results from CT-388-104 (NCT06628362), a randomized Phase II study evaluating once-weekly enicepatide in adults with type 2 diabetes and overweight or obesity.
The trial met its two primary endpoints, showing dose-dependent reductions in HbA1c and body weight at week 48. At the highest titrated dose of 24 mg, mean HbA1c fell by 2.65 percentage points from a baseline of 8.1%.
The response was greater among participants with poorer baseline glycemic control. In those with baseline HbA1c above 8.5%, the 24 mg dose produced a 4.13-percentage-point reduction at week 48.
By week 48, 90% of participants receiving 24 mg had reached an HbA1c of 6.5% or lower, while 62% achieved HbA1c below 5.7%, the range generally classified as normoglycemia.
Weight Loss Reached 15.5% at 48 Weeks
Enicepatide 24 mg produced a mean 15.5% reduction in body weight at week 48, with Roche reporting no demonstrable weight-loss plateau during the study period.
The reported 2.65-percentage-point HbA1c reduction and 15.5% weight loss represent mean changes from baseline in the enicepatide 24 mg group. Roche’s topline announcement does not report placebo-adjusted treatment differences for these efficacy endpoints. The placebo group had no treatment discontinuations because of adverse events, but that safety measure should not be interpreted as a placebo-adjusted efficacy comparison.
The findings also provide context for enicepatide’s earlier development in people with overweight or obesity without type 2 diabetes. In CT-388-103, the 24 mg dose produced a 22.5% placebo-adjusted weight loss at week 48 using the efficacy estimand, compared with 18.3% using the treatment-regimen estimand.
However, these figures should not be directly compared with the 15.5% result from CT-388-104 because the studies enrolled different populations and the reported measures use different estimands. Weight-loss outcomes across incretin trials can also vary according to baseline characteristics, diabetes status, study design and analysis methods.
Dual GLP-1/GIP Receptor Agonist
Enicepatide is an investigational once-weekly subcutaneous dual GLP-1/GIP receptor agonist being developed for obesity, type 2 diabetes and other cardiometabolic indications.
The molecule activates both GLP-1 and GIP receptors while minimizing β-arrestin recruitment. Roche reports that this biased signaling reduces receptor internalization and desensitization, a pharmacologic property intended to support sustained receptor activity.
GLP-1 and GIP pathways regulate glucose metabolism, appetite and energy balance, making combined receptor activation an established area of investigation in metabolic disease.
447 Patients Evaluated Over 48 Weeks
CT-388-104 enrolled 447 adults with type 2 diabetes and overweight or obesity in a randomized, double-blind, placebo-controlled, multicenter Phase II trial. Participants received once-weekly subcutaneous enicepatide or placebo for 48 weeks.
The dual primary endpoints were changes from baseline in HbA1c and body weight at week 48. The study showed dose-dependent effects across both measures.
Safety findings were broadly consistent with the known profile of incretin-based therapies. Gastrointestinal adverse events were the most common and were predominantly mild to moderate. Treatment discontinuation because of adverse events occurred in 2.0% of participants across the enicepatide groups compared with 0% in the placebo group. Roche reported no new safety signals.
Phase III Diabetes Program Planned
Roche Chief Medical Officer Levi Garraway said the company was encouraged by the extent of glycemic improvement and the proportion of participants reaching normoglycemia alongside sustained weight loss.
The company is already advancing enicepatide through two Phase III studies, ENITH-1 and ENITH-2, in chronic weight management. Roche plans to initiate a Phase III glycemic-control program and cardiovascular outcomes trials in the first half of 2027.
The CT-388-104 topline results strengthen the clinical development case for evaluating enicepatide in people with both diabetes and excess weight. Full study results, including detailed placebo-adjusted efficacy analyses, subgroup findings and the complete safety dataset, will be important for determining how the drug’s profile compares with existing incretin therapies as development progresses.
Reference
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, Roche, 22 September 2026
A Study of Enicepatide (CT-388) in Participants Who Are Overweight or Obese With Type 2 Diabetes Mellitus, ClinicalTrials.gov ID NCT06628362
About the Writer
Anamika Koshti (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, and evidence-based medicine. She has authored peer-reviewed publications on Alzheimer’s disease and PCOS, presented research at national conferences, and gained hands-on experience in medical content development and clinical data interpretation. She is committed to translating complex medical research into accurate, accessible content for healthcare professionals and patients.