Exclusion of older persons from randomized controlled trials in type 2 diabetes: A cross-sectional study.

Background: Prevalence of type 2 diabetes increases with age. Both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) promote the enrollment of older patients to randomized controlled trials (RCTs) in diabetes. The objective of this study was to assess the eligibility criteria limiting the inclusion of older adults to RCTs in type 2 diabetes.

Materials and methods: This cross-sectional analysis of ClinicalTrials.gov included phase 2, 3 and 4 RCTs of drugs and biologicals, with enrollment ≥100, registered at ClinicalTrials.gov and started from 2014 through 2023.

Results: A total of 278/594 (46.8%) trials had a limit of 90 years of age or less (primary outcome). The odds of the age limits were higher in RCTs funded from non-commercial sources (adjusted odds ratio (aOR), 2.83, 95% confidence interval (CI), 1.77-4.52; p < 0.001) and phase 2 trials (aOR, 2.38; 95% CI, 1.49-3.81; p < 0.001). A total of 542/594 (91.2%) trials had other relevant exclusion criteria, mostly those concerning comorbidities common in older patients (secondary outcome). However, none of the RCTs excluded patients with frailty which is a key factor determining the prognosis of older patients with diabetes. Only two trials enrolled solely older persons.

Conclusions: Most RCTs in type 2 diabetes have the eligibility criteria limiting the enrollment of older patients. The age limits should be eliminated and patients should be excluded based on scientifically justified criteria especially those concerning comorbidities and frailty. Moreover, the benefits and harms of new drugs in older patients with multimorbidity and/or frailty should be assessed in dedicated phase 4 trials.