Genentech Reports Positive Results from Phase 2 Trial of CT-388 in Obesity

On January 27, 2026, Genentech, a member of the Roche Group, announced positive topline results from the phase 2 CT388-103 trial, which investigated CT-388 for the treatment of obesity.1

CT-388 is an investigational dual GLP-1/GIP receptor agonist, designed for once-weekly subcutaneous administration in patients with type 2 diabetes, obesity, and other obesity-related comorbidities. The drug aims to regulate blood sugar and reduce appetite by targeting and activating receptors which integrate nutrient-derived signals to control energy homeostasis.1

“We are pleased to see such meaningful weight loss in people treated with CT-388,” Levi Garraway, MD, PhD, chief medical officer and head of global product development for Genentech, said in a statement. “The robust weight loss combined with a well-tolerated safety profile reinforces our confidence in the clinical development program as we advance to phase 3 trials.”1

The CT388-103 trial was a multi-center, randomized, double-blind, placebo-controlled, parallel group dose-finding study aiming to evaluate the safety and efficacy of CT-388 at low, middle, and high doses. To be eligible for inclusion, patients were required to be 18-75 years of age with a body mass index (BMI) ≥30 kg/m2, or a BMI ≥27 and <30 kg/m2 and a previous diagnosis of >1 from among prediabetes, hypertension, dyslipidemia, obstructive sleep apnea, and cardiovascular disease.2

Patients were excluded from the trial if they had a prior history of any type of diabetes mellitus, or a self-reported body weight change of >5 kg within 3 months before randomization. Additionally, patients were excluded if they had undergone any unbalanced or extreme diets within 3 months of screening or surgical treatment for obesity, among other criteria.2

CT388-103’s primary endpoint was the percent change in body weight from baseline to week 48. Secondary outcomes include the percentage of participants with body weight reduction ≥5%, ≥10%, ≥15%, ≥20%, and ≥25% from baseline to week 48, as well as absolute change in body weight, change in BMI from baseline, and change in waist circumference from baseline, among other endpoints.2

A total of 469 patients were enrolled in the trial and randomly assigned to either CT-388 at 1 of 5 doses (up to 24 mg) administered once weekly or matching placebo. Over 48 weeks, investigators observed a clear dose-response relationship on weight loss, as once-weekly injections of CT-388 resulted in placebo-adjusted weight loss of 22.5% (efficacy estimand) without reaching a plateau. For the treatment-regimen estimand, CT-388 achieved placebo-adjusted weight loss of 18.3% (P <.001).1

At week 48 for the highest does (24 mg), 95.7% of patients receiving CT-388 achieved a weight loss of ≥5%, 87% achieved ≥10%, 47.8% achieved ≥20%, and 26.1% achieved ≥30%. Additionally, 73% of participants with prediabetes at baseline achieved normal blood glucose at week 48 after treatment with CT-388 at 24 mg, compared to 7.5% in the placebo group.1

Treatment was well-tolerated during the study – most gastrointestinal-related adverse events were mild to moderate, consistent with other incretin-class medications. Discontinuation due to adverse events was low, with only 5.9% of the CT-388 arm and 1.3% of the placebo arm dropping out of the study.1

Genentech has also announced plans to present full results from the study at an upcoming medical congress. Another phase 2 investigation of CT-388 is currently ongoing, and Genentech plans to roll out the phase 3 clinical trial program at some point in Q1 2026.1

References

1. Genentech. Genentech Announces Positive Phase II Results for Its Dual GLP-1/GIP Receptor Agonist CT-388 in People Living With Obesity. BusinessWire. January 27, 2026. Accessed January 27, 2026. https://www.businesswire.com/news/home/20260126768216/en/Genentech-Announces-Positive-Phase-II-Results-for-Its-Dual-GLP-1GIP-Receptor-Agonist-CT-388-in-People-Living-With-Obesity

2. Carmot Therapeutics, Inc. A Study of CT-388 in Participants With Obesity or Overweight With at Least One Weight-Related Comorbidity. ClinicalTrials.gov Identifier: NCT06525935. Updated January 8, 2026. Accessed January 27, 2026. https://www.clinicaltrials.gov/study/NCT06525935