A Comparison of Individuals with Diabetes and EMPA-REG Trial Participants: Exploring Aspects of External Validity.

Background: There is increasing use of sodium glucose co-transporter 2 (SGLT2) inhibitors to treat diabetes. Since trials apply specific entry and exclusion criteria to ensure internal validity, comparisons of trial populations with nationally representative samples can inform the applicability of study findings to practice.

Objective: To compare individuals with diabetes from a nationally representative sample to patients who underwent randomization in the EMPA-REG trial. A secondary aim was to characterize what proportion of individuals prescribed an SGLT2 inhibitor in a nationally representative sample would have been included in the EMPA-REG trial.

Design: Retrospective cross-sectional study.

Participants: Adults with diabetes who took part in the National Health and Nutrition Examination Survey (NHANES) between 2011-2014 (primary analysis corresponding to EMPA-REG enrollment) and 2015-2018 (secondary analysis corresponding to contemporary sample).

Main Measures: The primary outcome was a comparison of demographic (age, sex, ethnicity, and pregnancy status), clinical (comorbidities and medication use), examination (weight, body mass index, and systolic and diastolic blood pressure), and laboratory (hgba1c, low- and high-density lipoprotein cholesterol, triglycerides, and estimated glomerular filtration rate) characteristics of NHANES respondents versus EMPA-REG trial participants. The secondary outcome was the proportion of NHANES respondents who had been prescribed an SGLT2 inhibitor that would have met inclusion criteria for the EMPA-REG trial.

Key Results: There were 655 and 48 respondents, representing a weighted sample of 21,849,775 and 1,062,573 individuals, included in the primary and secondary analyses, respectively. Overall, 7.6% (95% CI 4.8-10.6%) of 2011-2014 NHANES respondents would have met all EMPA-REG trial inclusion criteria. NHANES respondents and EMPA-REG participants differed across demographic, clinical, examination, and laboratory domains. Of NHANES respondents from 2015 to 2018 who were prescribed an SGLT2 inhibitor, 10.6% (95% CI <1-24.7%) would have met all inclusion criteria for the EMPA-REG trial.

Conclusions: The EMPA-REG population differed from a nationally representative sample, which could affect generalizability.