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    CT-388 (RG6640)

    Modality: Biased dual GLP-1/GIP receptor agonist

    Disease State: Type 2 Diabetes, Obesity

    Summary

    CT-388 is being investigated as an once-weekly subcutaneous injectable, dual glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide (GLP-1/GIP) receptor agonist for the treatment of obesity and type 2 diabetes (T2D). It was designed to have potent activity on both the GLP-1 and GIP receptors but with minimal to no ß-arrestin recruitment on either receptor. 1-2

    Clinical Trials

    Obesity with or without Type 2 Diabetes Mellitus
    Phase Enrollment Status Title
    Phase II Active, not recruiting A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multi-Center Phase 2 Study to Evaluate the Efficacy, Safety, and Tolerability of Once-Weekly CT-388 Administered Subcutaneously for 48 Weeks to Participants Who Are Overweight or Obese with Type 2 Diabetes Mellitus (CT-388-104) View Details
    Phase II Active, not recruiting A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multi-Center Phase 2 Study to Evaluate the Efficacy, Safety, and Tolerability of Once-Weekly CT-388 Administered for 48 Weeks to Participants with Obesity or Overweight with At Least One Weight-Related Comorbidity (CT-388-103) View Details

    Proposed Mechanism of Action

    CT-388 is being investigated as an once-weekly subcutaneous injectable, dual GLP-1/GIP receptor agonist for the treatment of obesity and type 2 diabetes (T2D).1,2 It was designed to have potent activity on both the GLP-1 and GIP receptors but with minimal to no ß-arrestin recruitment on either receptor. This biased signaling significantly minimizes receptor internalization and consequent desensitization, in which preclinical data suggests may lead to prolonged pharmacological activity.3

    CT-388 Signal-Biased, Dual GLP-1/GIP Receptor Agonist Being Developed for Obesity ± T2D and Other Weight-Related Comorbidities4,5

    Side by side image illustrating unbiased GLP-1RA signalling vs biased receptor modulator and the subsequent limitation of B-arrestin recruitment with retention of cAMP signaling potency1,6

    1. Chakravarthy MV, et al. Presented 59th European Association for the Study of Diabetes Annual Meeting. 2–6 October 2023; Hamburg, Germany. Presentation 75-LB;
    2. Chakravarthy MV, et al. Presented 60th European Association for the Study of Diabetes Annual Meeting. 9–13 September 2024; Madrid, Spain. Presentation LBA 65;
    3. Jones B et al. Nature Communications. 2018;9:160
    4. ClinicalTrials.gov A Study of CT-388 in Participants with Obesity or Overweight with At Least One Weight-Related Comorbidity (CT-388-103) [Internet; cited 2025 February]. Available from: https://clinicaltrials.gov/​study/​NCT06525935?intr=CT-388&rank=1
    5. ClinicalTrials.gov A Study of CT-388 in Participants Who Are Overweight or Obese with Type 2 Diabetes Mellitus (CT-388-104) [Internet; cited 2025 February]. Available from: https://clinicaltrials.gov/​study/​NCT06628362?intr=CT-388&rank=3
    6. Roche Pharma Day 2024 https://assets.roche.com/​f/​176343/​x/​f513f69de2/​pharma_day_20240930_final_online_v02.pdf

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    TOP

    • cAMP
      cyclic adenosine monophosphate

    • GLP-1
      Glucagon-like peptide-1

    • GIP
      Glucose-dependent insulinotropic polypeptide

    • GLP1R
      Glucagon-like peptide-1 receptor

    • T2D
      Type 2 Diabetes