Testing a new platform to screen disease-modifying therapy in type 1 diabetes

Area of Science:

• Endocrinology
• Immunology
• Clinical Trial Design

Background:

• Type 1 diabetes (T1D) research often requires lengthy recruitment and observation periods.
• Studies suggest a reserve of "sleeping" beta cells persists in individuals with longstanding T1D.
• Novel trial designs are needed to accelerate the testing of new T1D therapies.

Purpose of the Study:

• To evaluate the potential of specific agents to transiently induce insulin secretion from "sleeping" beta cells in T1D.
• To test a novel clinical trial platform for assessing T1D therapies.
• To explore beta-cell supportive and immunomodulatory agents for T1D.

Main Methods:

• A three-arm, non-randomized pilot study tested liraglutide, verapamil, and golimumab.
• Participants had undetectable C-peptide levels (<0.02 ng/mL) at baseline.
• Therapies were administered for 8-12 weeks, with outcomes assessed via mixed-meal tolerance tests (MMTT).

Main Results:

• No participants achieved the primary outcome of MMTT-stimulated C-peptide ≥ 0.02 ng/mL.
• Exploratory MRI analysis in the verapamil arm showed measure repeatability but no treatment effect.
• The golimumab arm experienced enrollment challenges due to pandemic-related immunotherapy concerns.

Conclusions:

• Short-term administration of liraglutide, verapamil, or golimumab did not induce detectable insulin secretion in individuals with longstanding T1D.
• The study highlights challenges in reawakening dormant beta cells.
• Further research is needed to identify effective strategies for beta-cell regeneration or activation in T1D.