Roche's Enicepatide Shows 15.5% Weight Loss in Diabetes Trial

On September 22, Roche disclosed findings from a mid-stage trial known as CT-388-104, reporting that its investigational compound enicepatide cut body weight by 15.5% on average and lowered HbA1c by 2.65 percentage points among participants with type 2 diabetes who were overweight or had obesity.³¹

Trial results

A total of 447 adults with type 2 diabetes and excess weight took part in the 48-week CT-388-104 trial. Roche reported that the 24 mg dose led to an average weight reduction of 15.5%, with participants still losing weight steadily rather than leveling off by the trial's conclusion.³

Participants on that same dosage saw their HbA1c decline by 2.65 percentage points, down from a starting average of 8.1%. Nine out of ten people in the 24 mg arm hit the blood-sugar goal of an HbA1c at or under 6.5%, while 62% returned to normal glucose levels—an HbA1c under 5.7%—placing them outside the range typically used to diagnose diabetes. In patients with poorer baseline control, defined as HbA1c above 8.5%, the reduction reached 4.13 percentage points.³²¹

Safety profile

Roche said side effects were predominantly mild to moderate gastrointestinal symptoms, consistent with other drugs in the same class, and that no new safety signals emerged during the trial.³¹⁴

According to figures Roche itself published, 2.0% of patients receiving enicepatide stopped treatment because of side effects, compared with none in the group given a placebo. However, Medical Daily reported that full placebo comparison figures had not been released alongside the initial results, leaving some safety context unconfirmed in independent reporting.³¹

Company strategy and market context

Roche obtained enicepatide through its 2023 acquisition of Carmot Therapeutics for $2.7 billion. Enicepatide works by acting on two hormone receptors, GLP-1 and GIP—an approach Roche and Reuters likened to Eli Lilly's tirzepatide (sold as Mounjaro and Zepbound), setting it apart from Wegovy, whose active ingredient semaglutide mainly targets GLP-1 alone, Reuters noted.²¹

Roche stated it is moving forward with late-stage trials called ENITH-1 and ENITH-2 focused on long-term weight control, and intends to launch additional Phase III research examining blood-sugar management and heart-related outcomes during the opening months of 2027. An earlier Phase II trial in people with obesity or overweight without diabetes, reported in June, showed 22.7% weight loss, according to Medical Dialogues.³¹⁴

Levi Garraway, Roche's Chief Medical Officer, said: "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." He added that the drug could offer "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."³

Teresa Graham, Chief Executive Officer of Roche Pharmaceuticals, said the results "reinforce our confidence in enicepatide and our ambition to rapidly advance its development for people living with obesity, diabetes, and cardiovascular disease," adding that Roche is "leveraging our integrated diagnostic and therapeutic expertise to build a competitive cardiometabolic portfolio." Reuters noted that the findings "reinforce Roche's ambitions to challenge Novo Nordisk and Eli Lilly, which currently dominate the global obesity-drug market," an industry estimated to be worth $100–150 billion by 2030, according to Reuters, or to exceed $100 billion annually within a decade, according to Medical Dialogues.³²⁴

Wider health context

Roche said diabetes affects nearly 600 million adults worldwide, with type 2 diabetes accounting for roughly 90% of cases. Roche noted that individuals with obesity face seven times the likelihood of developing type 2 diabetes compared with people at a normal weight, and that those with diabetes are two to four times more prone to conditions including high blood pressure, heart failure, stroke, and coronary artery disease.³¹