CT-388 Demonstrates Striking 22.5% Weight Loss in Phase 2 Obesity Trial

Genentech, a member of the Roche pharmaceutical group, has released compelling Phase 2 trial outcomes for CT-388, an investigational obesity treatment that demonstrates significant clinical potential. The once-weekly injectable, a dual GLP-1/GIP receptor agonist, showcased a placebo-adjusted weight loss of 22.5% at 48 weeks—a result that substantially exceeds current standard treatments in this therapeutic class. This breakthrough achievement marks an important milestone as the drug progresses toward advanced clinical development for obesity, type 2 diabetes, and related metabolic conditions.

Compelling Efficacy Results Across Weight Loss Benchmarks

The Phase 2 trial (CT388-103) demonstrates impressive stratification across multiple weight loss thresholds. Among patients receiving the 24 mg weekly dose, nearly all participants—95.7%—achieved at least 5% weight reduction, while 87% surpassed the 10% threshold. More notably, 47.8% lost 20% or more of their body weight, and 26.1% achieved 30% or greater weight loss—results that continue to improve at the 48-week endpoint without signs of plateau.

The drug demonstrates transformative metabolic outcomes beyond weight reduction alone. At the trial’s conclusion, 54% of participants normalized their BMI below the obesity threshold (≤30 kg/m²), compared to just 13% in the placebo cohort. Perhaps more striking, pre-diabetic participants achieved normal glucose levels at rates four times higher than placebo—73% versus 7.5%—suggesting significant potential for diabetes prevention and reversal.

Safety Profile Supports Continued Development

CT-388 demonstrates a favorable tolerability pattern consistent with its mechanistic class. Gastrointestinal side effects, while present, remained mild to moderate in most cases and align with expected safety signals for GLP-1/GIP agonists. Critical to clinical progression, only 5.9% of patients discontinued treatment due to adverse events compared with 1.3% in the placebo group—a manageable discontinuation rate that supports the drug’s clinical viability.

From Acquisition to Phase 3: CT-388’s Clinical Trajectory

Genentech acquired CT-388 through its January 2024 acquisition of Carmot Therapeutics, obtaining a Phase 2–ready asset that has now validated its promise. Building on these results, a second Phase 2 study (CT388-104) is actively enrolling patients with obesity or overweight status who also have type 2 diabetes, addressing a population with particularly high clinical need.

The clinical program demonstrates momentum as Phase 3 trials—designated Enith1 and Enith2—are scheduled to begin this quarter. “The robust weight loss combined with a well-tolerated safety profile reinforces our confidence in the clinical development program as we advance to Phase III trials,” stated Levi Garraway, chief medical officer and head of Global Product Development at Roche.

This progression underscores the growing importance of obesity treatment in global health, with projections suggesting that by 2035, more than half the world’s population will be living with excess weight or obesity. CT-388 represents one of several investigational approaches aimed at addressing this expanding pandemic of metabolic disease.