Roche’s experimental dual GLP-1/GIP receptor agonist CT-388 has demonstrated substantial weight loss in a mid-stage clinical trial, reinforcing the Swiss drugmaker’s decision to advance the asset into phase 3 studies later this quarter.
In a phase 2 trial involving 469 adults with obesity or who were overweight, Roche evaluated three subcutaneous doses of CT-388 against placebo. The primary endpoint measured the placebo-adjusted percentage change in body weight from baseline to Week 48. Patients receiving the highest dose, 24 mg, achieved a 22.5% reduction in body weight over the study period.
The results place CT-388 broadly in line with leading therapies in the class, including Eli Lilly’s GLP-1/GIP agonist Zepbound, which produced a 20.9% reduction in body weight at 36 weeks with its 15-mg dose.
Roche reported that under the treatment-regimen estimand, placebo-adjusted weight loss reached 18.3% at 48 weeks. Importantly, the company said it observed no evidence of a weight-loss plateau by the end of the study period, according to a Jan. 27 statement.
Among participants receiving the highest dose, 95.7% achieved more than 5% weight loss, while 26.1% lost more than 30% of their body weight. Although Roche is reserving full trial data for presentation at a future medical conference, it characterized CT-388 as generally well tolerated. Most gastrointestinal-related adverse events were mild to moderate and consistent with those typically seen across the incretin drug class.
Treatment discontinuation occurred in 5.9% of patients receiving CT-388, compared with 1.3% in the placebo group.
“We are pleased to see such meaningful weight loss in people treated with CT-388,” Roche Chief Medical Officer Levi Garraway, M.D., Ph.D., said in a statement. “The robust weight loss combined with a well-tolerated safety profile reinforces our confidence in the clinical development programme as we advance to phase 3 trials.”
Roche confirmed it plans to initiate two phase 3 obesity studies for CT-388 this quarter. The company first outlined its late-stage ambitions for the asset during its Pharma Day in September 2025, where it detailed a broader strategy to become a “top three” player in the obesity market by leveraging combinations across its pipeline.
One such strategy includes pairing CT-388 with petrelintide, a long-acting amylin analog designed to address nausea, a leading cause of treatment discontinuation for current weight-loss drugs. Roche struck a $1.6 billion upfront deal with Zealand Pharma last year to co-develop and co-commercialize petrelintide.
CT-388 originated outside Roche, entering the company’s portfolio through its $2.7 billion acquisition of Carmot Therapeutics in 2023. Earlier this month, Roche also paid $100 million to Structure Therapeutics for a nonexclusive license to patents related to CT-996, an oral GLP-1 candidate also inherited from the Carmot deal.
Roche has signaled that it does not intend to rely on a single blockbuster to compete in the obesity market. In September, Manu Chakravarthy, M.D., Ph.D., Roche’s global head of cardiovascular, renal and metabolism product development, said the complexity of obesity requires a diversified approach.
“If you only had that, you would be severely handicapped in addressing the complexity and the heterogeneity of what we know the obesity market is,” he told Fierce at the time.
Analysts at ODDO BHF welcomed the phase 2 data, calling it a “material pipeline upgrade” for Roche. In a Jan. 27 note, the firm said the results justify Roche’s investments in obesity and suggested CT-388 could rank among the most effective therapies in the field if the findings are confirmed in phase 3 trials.
