Roche's Enicepatide Type 2 Diabetes Trial Meets HbA1c and Weight Goals

Roche’s enicepatide type 2 diabetes program cleared its Phase II hurdle, with the investigational dual GLP-1/GIP receptor agonist meeting both primary endpoints in the CT-388-104 trial. Topline results, released 22 September 2026, showed dose-dependent reductions in HbA1c and body weight at 48 weeks.

At the highest titrated dose of 24 mg, enicepatide cut HbA1c by 2.65% from a baseline of 8.1%. In that arm, 90% of patients reached an HbA1c of 6.5% or lower, the diagnostic threshold for type 2 diabetes, and 62% achieved normoglycemia below 5.7%, a non-diabetic range. For patients who started with poor glycemic control above 8.5%, the 24 mg dose delivered a 4.13% HbA1c reduction.

Weight loss tracked the glucose results. The 24 mg arm shed a mean 15.5% of body weight by week 48, with no plateau in sight. The safety profile stayed in line with the incretin class: mostly mild to moderate gastrointestinal effects, and a 2.0% discontinuation rate for adverse events, against 0.0% on placebo.

Enicepatide type 2 diabetes trial design

CT-388-104 (NCT06628362) was a randomized, double-blind, placebo-controlled, parallel-group, multicenter Phase II study. It evaluated once-weekly subcutaneous enicepatide over 48 weeks in 447 adults living with type 2 diabetes and overweight or obesity. The dual primary endpoints were change from baseline in HbA1c and body weight at week 48.

A biased receptor design

Enicepatide is designed to activate both GLP-1 and GIP receptors strongly while recruiting little to no beta-arrestin on either. That bias is meant to slow receptor internalization and desensitization, which Roche expects to prolong the drug’s activity. The mechanism taps the receptors that integrate nutrient signals to control appetite, blood sugar, and energy balance.

Late-stage plans

Roche is running two Phase III studies in chronic weight management, ENITH-1 and ENITH-2, and plans to start a Phase III glycemic-control program and cardiovascular outcomes trials in the first half of 2027.

“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,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development.

“These results reinforce our confidence in enicepatide and our ambition to rapidly advance its development for people living with obesity, diabetes, and cardiovascular disease,” said Teresa Graham, Chief Executive Officer, Roche Pharmaceuticals.

The burden of diabetes and obesity

Nearly 600 million adults worldwide live with diabetes, and type 2 diabetes makes up approximately 90% of cases, with incidence rising fastest in low- and middle-income countries. Excess body fat drives insulin resistance, and people with obesity are seven times more likely to develop type 2 diabetes than those with a normal body mass index.

The complications are severe. People with diabetes face a 2 to 4 times higher risk of hypertension, heart failure, stroke, and coronary artery disease. Prolonged high blood glucose damages blood vessels and nerves, and untreated diabetes can lead to blindness, kidney failure, strokes, and amputations. An HbA1c of 6.5% marks the diagnostic threshold for diabetes; below 5.7% is normoglycemia, and 5.7% to 6.4% defines prediabetes.

Source: Roche media release, 22 September 2026.