January 27, 2026
Finance

Roche’s CT-388 Demonstrates Promising Weight Loss Results in Phase 2 Obesity Trial

Novel dual GLP-1/GIP receptor agonist achieves significant weight reduction with high tolerability in non-diabetic overweight and obese adults

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Summary

Roche Holdings AG has unveiled initial results from its Phase 2 clinical trial evaluating CT-388, an innovative once-weekly injectable therapy targeting obesity. The trial showed substantial placebo-adjusted weight loss over 48 weeks, marked by a clear dose-response effect and a strong safety profile, highlighting CT-388's potential in managing obesity and related metabolic disorders.

Key Points

Phase 2 trial CT388-103 tested CT-388, a dual GLP-1/GIP receptor agonist developed for obesity and related conditions.
In 469 overweight or obese adults without diabetes, CT-388 induced significant dose-dependent weight loss after 48 weeks, with up to 22.5% placebo-adjusted reduction.
At the highest 24 mg dose, 87% of participants lost at least 10% of body weight and 73% of pre-diabetics normalized blood glucose levels.
The treatment was generally well-tolerated, with mostly mild to moderate gastrointestinal side effects and low discontinuation rates due to adverse events.

Roche Holdings AG presented encouraging topline data from the CT388-103 Phase 2 study of its investigational compound CT-388, designed to combat obesity. CT-388 is a once-weekly, subcutaneous injectable medication functioning as a dual receptor agonist for GLP-1 and GIP, developed to address obesity, type 2 diabetes, and associated comorbidities.


The clinical trial enrolled 469 adult participants characterized by obesity (body mass index, or BMI, of 30 or higher) or those overweight (BMI ranging from 27 to just under 30) with one or more weight-associated comorbidities but without a diagnosis of type 2 diabetes. The study assessed five cohorts subjected to varying dosing escalation regimens, with the maximum dose reaching 24 mg.

The study’s principal endpoint measured the percentage change in body weight from baseline to week 48. Findings indicated that weekly injections of CT-388, escalated up to 24 mg, yielded a significant and clinically relevant placebo-corrected weight reduction of 22.5% based on the efficacy estimand, with weight loss continuing beyond the 48-week time point without apparent plateauing.

A pronounced dose-dependent relationship was observed, emphasizing higher weight loss with increased dosage levels. Using the treatment regimen estimand, CT-388 achieved a placebo-adjusted weight decline of 18.3%, a result deemed statistically significant (p-value below 0.001).

On the 24 mg dose at 48 weeks, nearly 96% of treated participants lost more than 5% of their body weight. Remarkably, 87% experienced weight reductions exceeding 10%, 47.8% saw a loss over 20%, and 26.1% achieved reductions beyond 30%. Additionally, among individuals classified as pre-diabetic at the study’s start, 73% receiving the 24 mg dose normalized their blood glucose levels by week 48, compared with only 7.5% in the placebo group.

The safety profile of CT-388 was favorable, with gastrointestinal events being the most common adverse reactions, predominantly mild to moderate in severity, aligning with expectations for meds targeting incretin pathways. Treatment discontinuations attributable to adverse events were limited, recorded at 5.9% for CT-388 arms versus 1.3% in placebo.


CT-388’s progress follows Roche’s 2023 acquisition of Carmot Therapeutics, through which this therapeutic asset entered Roche’s pipeline. The company accelerated CT-388’s clinical development trajectory and granted it fast-track status, underscoring its strategic importance within Roche’s obesity treatment portfolio.

Beyond offering standalone efficacy, CT-388 is envisioned as an enabling component for combination regimens, including with petrelintide, indicating a broader role in Roche’s obesity pipeline expansion.

An ongoing Phase 2 trial, designated CT388-104, is exploring CT-388’s effects in obese participants also diagnosed with type 2 diabetes. Roche anticipates launching pivotal Phase 3 programs, named Enith1 and Enith2, in the current quarter to further evaluate the compound’s potential in obesity management.


With an increasing competitive landscape in the weight-loss pharmaceutical market, Roche’s proactive development of CT-388 aligns with its objective to establish a leadership position moving forward, directly contending with companies like Eli Lilly and Novo Nordisk.

As of the most recent trading session, Roche Holdings AG’s stock was valued at $56.12.

Risks
  • The data is from a Phase 2 study, with ongoing Phase 3 trials required to confirm efficacy and safety at larger scale.
  • Safety profile includes gastrointestinal adverse events common to incretin class medicines, which may affect patient adherence.
  • The treatment is tested primarily in patients without type 2 diabetes; effects in diabetic populations are under separate investigation and not yet fully established.
  • Market competition is intense with multiple players advancing obesity therapies, making commercial success uncertain despite promising results.
Disclosure
Education only / not financial advice
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