Findings
Traditional endpoints like HbA1c are insufficient to assess hypoglycemia’s impact on quality of life and daily function for diabetes patients.
CGM offers continuous, objective glucose monitoring, enabling the detection of glycemic variability and hypoglycemic episodes in real-time.
Stakeholders, including regulators, industry, and patients, emphasize the need for CGM-derived endpoints to complement traditional biomarkers.
Challenges include standardizing hypoglycemia definitions, creating shared databases for CGM data, and addressing technical limitations at lower glucose levels.
Patient-reported outcomes (PROs) combined with CGM data can provide a comprehensive view of treatment effects but require further validation.

Recommendations
Establish consensus definitions of hypoglycemia and standardized metrics for CGM-based endpoints, such as percent reduction in hypoglycemia duration or frequency.
Create shared CGM databases to facilitate data analysis and validation of novel endpoints across clinical trials.
Conduct CGM-based studies to correlate hypoglycemia metrics with meaningful patient outcomes, including wellness, disease burden, and functional impacts.
Integrate CGM endpoints into regulatory submissions alongside traditional measures like HbA1c to demonstrate comprehensive treatment effects.
Collaborate with stakeholders to address technical challenges, such as CGM accuracy at lower glucose levels, and explore their application in pediatric populations in the future.

Regulatory Considerations
Validate CGM-derived endpoints to align with regulatory requirements, demonstrating their predictive value for severe hypoglycemia and other meaningful outcomes.
Engage regulators early to ensure CGM metrics complement existing endpoints like HbA1c and address unmet needs in diabetes trials.
Address technical limitations, such as CGM calibration and data accuracy at low glucose levels, to meet evidentiary standards for clinical trial endpoints.
Develop and document statistical methodologies for analyzing CGM-derived endpoints, including handling missing data and variability.
Include patient-reported outcomes and quality-of-life measures to contextualize CGM data in regulatory submissions.