Roche's Dual GLP-1/GIP Agonist CT-388 Delivers 22.5% Weight Loss in Phase II Trial, Paving Way for Phase III

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Basel, Switzerland – January 27, 2026 – Roche, the global biotechnology leader, announced positive topline results from its Phase II trial of CT-388, an investigational once-weekly injectable dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, demonstrating substantial weight loss in adults with obesity. The CT388-103 study, involving 469 participants, met its primary endpoint with a placebo-adjusted mean weight reduction of 22.5% at 48 weeks on the highest dose of 24 mg (efficacy estimand), signaling a potential new contender in the booming anti-obesity market dominated by drugs like Eli Lilly’s Zepbound.

Trial Design and Key Findings

The CT388-103 trial was a multicenter, randomized, double-blind, placebo-controlled, parallel-group dose-finding study targeting adults with obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) with at least one weight-related comorbidity, excluding those with type 2 diabetes. Participants received subcutaneous injections of CT-388 at low, middle, or high doses across five up-titration cohorts, or placebo, over 48 weeks.

CT-388 achieved statistically significant placebo-adjusted weight loss without plateauing, with a clear dose-response relationship. At the 24 mg dose, results included: 95.7% of participants losing ≥5% body weight, 87% losing ≥10%, 47.8% losing ≥20%, and 26.1% losing ≥30%. For the treatment-regimen estimand (accounting for discontinuations), weight loss was 18.3% (p<0.001). Notably, 54% on 24 mg achieved obesity resolution (BMI <30 kg/m²), compared to 13% on placebo.

Among pre-diabetic participants at baseline, 73% on 24 mg CT-388 normalized blood glucose levels by week 48, versus 7.5% on placebo, highlighting metabolic benefits.

Roche Executive Commentary

“We are pleased to see such meaningful weight loss in people treated with CT-388,” stated Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “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.”

Roche has fast-tracked CT-388 since acquiring it via Carmot Therapeutics in 2023, positioning it as a standalone therapy and potential combination partner for petrelintide, an amylin analog in its pipeline.

Understanding GLP-1/GIP Agonists

GLP-1 and GIP are gut hormones that regulate appetite, glucose metabolism, and energy balance—like natural traffic signals telling the body when to eat less and use energy efficiently. Dual agonists like CT-388 mimic both, activating receptors to curb hunger and improve insulin sensitivity, unlike single GLP-1 drugs such as semaglutide (Wegovy).

CT-388’s design emphasizes biased signaling: potent receptor activation with minimal β-arrestin recruitment, reducing desensitization for sustained effects—like a dimmer switch that stays on longer without flickering out. This differentiates it in a class where Lilly’s tirzepatide (Zepbound/Mounjaro) set benchmarks with ~20-22% weight loss in trials.

Safety Profile and Tolerability

CT-388 showed a profile consistent with incretin-based therapies, with most gastrointestinal adverse events (nausea, vomiting, diarrhea) mild-to-moderate. Discontinuation due to adverse events was low: 5.9% in CT-388 arms versus 1.3% in placebo. No new safety signals emerged, supporting once-weekly dosing feasibility.

Broader Context: Obesity Crisis and Treatment Landscape

Obesity affects over 1 billion people globally, projected to impact more than half the world’s population by 2035, driving comorbidities like diabetes, heart disease, and cancer. Current options like lifestyle changes yield ~5-10% loss, often regained, while GLP-1s offer more but face supply shortages and high costs (~$1,000/month).

Roche enters a $150 billion market led by Novo Nordisk and Lilly, whose drugs transformed outcomes but sparked side effect concerns (e.g., gastroparesis) and muscle loss debates. CT-388’s non-plateauing loss and glycemic improvements position it competitively, though full data awaits congress presentation.

Expert Perspectives

Dr. Fatima Cody Stanford, an obesity medicine specialist at Massachusetts General Hospital (not involved in the trial), noted: “22.5% placebo-adjusted loss rivals tirzepatide’s pivotal data, especially without plateau—a key for long-term management. The pre-diabetes reversals are promising for cardiometabolic health.” However, she cautioned that Phase II sizes limit generalizability, and real-world adherence may differ.

Dr. Louis Aronne, director of the Comprehensive Weight Control Center at Weill Cornell (independent commentator), added: “Roche’s biased signaling could mean fewer GI issues long-term, but Phase III must confirm durability and cardiovascular outcomes, as seen in SELECT trial for semaglutide.”

Public Health Implications

If validated in Phase III (Enith1/Enith2, starting Q1 2026), CT-388 could expand access to effective pharmacotherapy, reducing healthcare burdens estimated at $2 trillion annually globally. For patients, it means potential 20-30% sustained loss—enough to remit obesity in many—plus diabetes prevention, but only alongside diet/exercise.

In India, where 30% of adults face obesity amid rising diabetes (101 million cases), affordable options are critical; Roche’s diagnostics expertise could aid personalized use. Consumers should view this as hope, not a magic pill—lifestyle remains foundational.

Limitations and Next Steps

Phase II excluded type 2 diabetes patients (ongoing in CT388-104), limiting insights there; diverse demographics need Phase III confirmation. Weight loss metrics used estimands; real-world (treatment-regimen) 18.3% is realistic but lower. Long-term data on muscle preservation, CV risk, and costs are pending.

Full results will present soon; a diabetes Phase II and Phase III obesity trials loom. Investors reacted tepidly, citing competition, but analysts see pipeline value.

Medical Disclaimer: This article is for informational purposes only and should not be considered medical advice. Always consult with qualified healthcare professionals before making any health-related decisions or changes to your treatment plan. The information presented here is based on current research and expert opinions, which may evolve as new evidence emerges.