How many people with type 2 diabetes fulfil the eligibility criteria for randomized, controlled trials of insulin glargine 300 U/mL in a real-world setting?

Abstract

Randomized controlled trial (RCT) populations often do not reflect those typically seen in clinical practice. This retrospective, observational cohort study analysed the real-world data of people with type 2 diabetes (T2DM) prescribed basal insulin analogues from electronic medical records (EMRs) in the Explorys database, which includes data from 39 integrated healthcare systems in the United States, to determine how representative selected RCTs investigating insulin glargine 300 U/mL (Gla-300) are of T2DM populations in a real-world setting. Applying eligibility criteria derived from the EDITION 1, 2 and 3 (Gla-300 vs. insulin glargine 100 U/mL [Gla-100]) and BRIGHT (Gla-300 vs. insulin degludec) RCTs, we observed that only 17% (33 345/191 218) of people captured in the real-world database would have been eligible for such trials. Those who were ineligible tended to be older, had more comorbidities and a higher baseline hypoglycaemia rate than the eligible group. Using another large US EMR database (Optum Humedica) as corroboration, we found that 15% (36 285/235 697) would have been eligible to participate in the EDITION/BRIGHT RCTs. Furthermore, only 7% (1734/24 547) would have been eligible for the CONCLUDE (insulin degludec vs. Gla-300) RCT. Our findings remind us of the value of real-world data studies, complementing the results of RCTs, and providing additional insights into groups who would typically be excluded from RCTs.

Keywords: basal insulin; cohort study; database research; randomized trial; type 2 diabetes.

FIGURE 1

Schematic showing A, participant selection and percentage of people with type 2 diabetes (T2DM) in the Explorys database eligible to participate in randomized controlled trials (RCTs) using eligibility criteria adapted from the EDITION 1, 2 and 3 and BRIGHT trials, and B, the percentage of people with T2DM in the Optum Humedica database eligible to participate in RCTs using eligibility criteria adapted from the EDITION 1, 2 and 3 and BRIGHT trials and adapted from CONCLUDE. Main analysis: All exclusion criteria apply 12 months prior to the index date. Uncontrolled hypertension defined as systolic blood pressure >180 mmHg and/or diastolic blood pressure >95 mmHg at any point in the 12 months prior to the index date. Additional analysis: Eligibility criteria adapted from the CONCLUDE RCT are shown in Table S3. BI, basal insulin; DBP, diastolic blood pressure; Gla‐300, insulin glargine 300 U/mL; HbA1c, glycated haemoglobin; SBP, systolic blood pressure