Abstract
Purpose :
Hyperglycemia is a risk factor for the development and progression of diabetic macular edema/retinopathy (DME/DR). Glycated hemoglobin A1c (A1c) reflects average blood glucose level over 8–12 weeks, and is the most clinically used biomarker for monitoring glycemic control in diabetics. We investigated methods by which DR/DME and major diabetes clinical trials monitored and reported A1c.
Methods :
We identified landmark diabetes and DR/DME clinical trials with minimum duration of 1 year from references cited from the American Academy of Ophthalmology’s Diabetic Retinopathy Preferred Practice Pattern, Diabetic Retinopathy Clinical Research Network, and Clinicaltrials.gov. Study design and reporting features were evaluated.
Results :
We identified 47 diabetic eye trials (23 DR/24 DME) and 10 landmark diabetes glucose control trials. The % of DR/DME and diabetes trials with A1c enrollment criteria was 53% (25/47) and 30% (3/10), respectively. Of DR/DME trials beginning years <2000, 2000-2010 and >2010, the percentage with A1c enrollment criteria was 0% (0/4), 57% (8/14), and 59% (17/29), respectively. Of the DR/DME and diabetes trials that collected A1c, the % that reported A1c assay methods was 21% (7/34) and 89% (8/9), respectively. The % of DR/DME and diabetes trials that collected A1c at baseline and endpoint was 45% (19/42) and 80% (8/10), respectively. Of studies with >1 year duration, the % of DR/DME and diabetes trials that collected A1c at least 1/year was 55% (11/20) and 67% (6/9), respectively. Of the DR/DME trials with >1 year duration, those that began years <2000, 2000-2010 and >2010 and sampled A1c at least once a year was 33% (1/3), 33% (4/12), and 67% (6/9) of trials, respectively. Of DR/DME and diabetes trials that statistically evaluated the relationship between baseline A1c and treatment effect/disease progression, 67% (8/12) and 100% (5/5) of trials found significant associations, respectively.
Conclusions :
The reporting, methods and enrollment criteria related to A1c varies across diabetes trials and over time. There was a trend of more frequent A1c monitoring across all diabetic eye trials over time. However, diabetes eye trials had less frequent A1c evaluation compared to major diabetes trials, despite more frequent disease progression assessments in eye trials. Further work should be considered to evaluate the optimal methodology of hyperglycemia monitoring in diabetes clinical trials.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.