[Ad hoc announcement pursuant to Art. 53 LR] 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
Phase II data show large HbA1c and weight reductions for enicepatide, supporting Roche’s move into multiple late-stage cardiometabolic trials.
Rhea-AI Summary
Roche (RHHBY) reported positive 48‑week Phase II results for dual GLP‑1/GIP agonist enicepatide in adults with type 2 diabetes and overweight or obesity on 22 September 2026.
In the CT-388-104 trial, once-weekly enicepatide met both primary endpoints, showing dose-dependent reductions in HbA1c and body weight versus baseline. At the highest 24 mg dose, mean HbA1c fell by 2.65 percentage points from a baseline of 8.1%. In participants with poor baseline control (HbA1c >8.5%), the 24 mg dose produced a 4.13 percentage point HbA1c reduction.
By week 48, 90% of patients on 24 mg reached ≤6.5% HbA1c and 62% achieved normoglycemia (<5.7%). Mean weight loss at 48 weeks on 24 mg was 15.5% without a demonstrable plateau. Safety and tolerability were consistent with established incretin therapies, with mainly mild-to-moderate gastrointestinal events and a 2.0% discontinuation rate in enicepatide arms. Roche is running two Phase III studies in chronic weight management and plans a Phase III glycemic-control programme and cardiovascular outcomes trials in 2027.
Positive
- HbA1c reduction of 2.65 percentage points at 48 weeks on 24 mg from 8.1% baseline
- HbA1c reduction of 4.13 percentage points at 48 weeks in poorly controlled subgroup (baseline >8.5%)
- 90% of patients on 24 mg reached ≤6.5% HbA1c at week 48
- 62% of patients on 24 mg achieved normoglycemia (HbA1c <5.7%) at week 48
- 15.5% mean body-weight loss at 48 weeks on 24 mg without demonstrated plateau
- Adverse-event discontinuation rate only 2.0% in enicepatide arms, 0.0% on placebo
- Two ongoing Phase III trials in chronic weight management and further Phase III and cardiovascular outcome trials planned for 2027
Negative
- None.
AI-generated analysis. How Rhea-AI works. Not financial advice.
- At the highest dose (24 mg), enicepatide achieved a mean HbA1c reduction of
2.65% at 48 weeks, highlighting its potential for best-in-disease glycemic control - In patients with poor baseline glycemic control (HbA1c >
8.5% ), enicepatide 24 mg led to an HbA1c reduction of4.13% at 48 weeks - By week 48,
90% of patients in the 24 mg enicepatide arm met the T2D glycemic target of ≤6.5% HbA1c, while62% achieved normoglycemia (HbA1c <5.7% ) - At the highest 24 mg dose, enicepatide achieved a mean weight loss of
15.5% at 48 weeks, without a weight loss plateau - Enicepatide demonstrated a safety and tolerability profile consistent with the incretin class, with low discontinuation rates and no new safety signals identified
Basel, 22 September 2026 - Roche (SIX: RO, ROP; OTCQX: RHHBY) today announced positive topline results from CT-388-104, a Phase II clinical trial evaluating enicepatide (CT-388), an investigational, once-weekly dual GLP-1/GIP receptor agonist, in adults living with type 2 diabetes (T2D) and overweight or obesity. In the study, enicepatide met both primary endpoints, delivering dose-dependent and clinically meaningful reductions in blood glucose and body weight at 48 weeks. Patients receiving the highest titrated dose (24 mg) achieved an HbA1c reduction of
The safety and tolerability profile of enicepatide was consistent with other established incretin-based therapies, with the most common adverse events being predominantly mild-to-moderate gastrointestinal effects. In addition, the treatment discontinuation rate due to adverse events was low (
The totality of data positions enicepatide, a unique dually biased GLP-1/GIP receptor agonist, as a differentiated molecule designed for potentially greater efficacy with a favorable safety profile.
“We are highly encouraged by the efficacy demonstrated by enicepatide in this Phase II study, including the meaningful proportion of patients reaching normalised glucose levels within less than a year of treatment,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “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.”
Roche is advancing a broad late-stage development program for enicepatide, including two ongoing Phase III studies in chronic weight management (ENITH-1 and ENITH-2) and plans to initiate a Phase III glycemic-control program and cardiovascular outcomes trials in the first half of 2027.
“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. “As we expand into late-stage clinical studies and explore novel combinations, we are leveraging our integrated diagnostic and therapeutic expertise to build a competitive cardiometabolic portfolio — aiming to protect people from early metabolic dysfunction to advanced organ damage, ultimately reducing the global disease burden.”
About the enicepatide 104 Phase II study [NCT06628362]
The CT-388-104 study is a randomized, double-blind, placebo-controlled, parallel-group, multi-center Phase II trial evaluating the efficacy, safety, and tolerability of once-weekly enicepatide administered subcutaneously for 48 weeks in 447 adults living with T2DM and overweight or obesity. The dual primary outcomes are changes from baseline in HbA1c and body weight at week 48.
About enicepatide
Enicepatide is an investigational once-weekly subcutaneous injectable, dually biased GLP-1/GIP receptor agonist in development for the treatment of obesity, type 2 diabetes, and additional cardiovascular indications. It aims to reduce appetite and regulate blood sugar by selectively targeting and activating both receptors which integrate nutrient-derived signals to control energy homeostasis. Enicepatide was designed to have potent activation of both GLP-1 and GIP receptors, but with minimal to no ß-arrestin recruitment on either receptor. This biased signalling significantly minimises receptor internalisation and consequent desensitisation, which is expected to lead to prolonged pharmacological activity.
About Obesity and T2D
Obesity and Type 2 diabetes are among the most urgent global public health challenges. Prevalence continues to rise, driving significant morbidity, disability and premature death.
Obesity is a major risk factor for T2D because excess body fat contributes significantly to insulin resistance and dysfunction of the cells that produce insulin. Consequently, people living with obesity are seven times more likely to develop T2D than those with a normal body mass index.
Diabetes is a condition that now affects nearly 600 million adults worldwide with T2D representing approximately
One of the most serious health risks of diabetes is cardiovascular disease. People living with diabetes face a 2-4 times higher risk of hypertension, heart failure, stroke, and coronary artery disease than those without it. Prolonged high blood glucose silently damages blood vessels and nerves, making cardiovascular complications more likely, more frequent and more severe over time.
HbA1c (glycated hemoglobin) is measuring the average blood glucose levels over the past two to three months. HbA1c of
About Roche
Roche (SIX: RO, ROP; OTCQX: RHHBY) is a healthcare company uniquely placed to prevent, stop and cure diseases by uniting leading science and technology across diagnostics, medicines and digital solutions.
Roche was founded in Basel, Switzerland in 1896 and today is a leading provider of transformative medicines and diagnostics for millions of people in over 150 countries around the world. It is dedicated to tackling healthcare challenges that place the greatest strain on patients, families, communities and healthcare systems. Across its Diagnostics and Pharmaceutical divisions, Roche focuses on areas including oncology, neurology, cardiovascular and metabolic diseases, ophthalmology, infectious diseases and immunology with the aim of providing real and positive change for patients, the people they love and the professionals who care for them.
Genentech in the United States is a fully owned subsidiary in the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, a major innovator in the Japanese therapeutic antibody market.
For more information, please visit www.roche.com.
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Attachment
FAQ
AI-generated questions and answers. How Rhea-AI works. Not financial advice.
What was the design and size of the CT-388-104 Phase II study?
The CT-388-104 study is a randomized, double-blind, placebo-controlled, parallel-group, multi-center Phase II trial. It evaluates once-weekly subcutaneous enicepatide for 48 weeks in 447 adults living with type 2 diabetes and overweight or obesity. The dual primary outcomes are changes from baseline in HbA1c and body weight at week 48.
What safety profile did enicepatide show in this Phase II trial?
Enicepatide showed a safety and tolerability profile consistent with established incretin-based therapies. The most common adverse events were predominantly mild-to-moderate gastrointestinal effects. Treatment discontinuation due to adverse events was 2.0% in enicepatide arms and 0.0% in the placebo arm, and no new safety signals were identified.
For which indications is Roche developing enicepatide beyond type 2 diabetes?
Enicepatide is being developed for the treatment of obesity, type 2 diabetes and additional cardiovascular indications. Roche is conducting two Phase III trials in chronic weight management (ENITH-1 and ENITH-2) and plans to start a Phase III glycemic-control programme and cardiovascular outcomes trials in the first half of 2027.
How does enicepatide work as a dual GLP-1/GIP receptor agonist?
Enicepatide is a once-weekly subcutaneous injectable, dually biased GLP-1/GIP receptor agonist. It aims to reduce appetite and regulate blood sugar by selectively targeting and activating both receptors, which integrate nutrient-derived signals to control energy homeostasis. It was designed for potent activation of both receptors with minimal to no β-arrestin recruitment, which is expected to minimise receptor internalisation and desensitisation and thereby prolong pharmacological activity.