Eligibility varies among the 4 sodium-glucose cotransporter-2 inhibitor cardiovascular outcomes trials: implications for the general type 2 diabetes US population

Am J Manag Care. 2018 Apr;24(8 Suppl):S138-S145.

Abstract

Objectives: Guidance to industry from the FDA requires studies to evaluate the cardiovascular safety of novel type 2 diabetes (T2D) medications. Although the objectives of such cardiovascular outcomes trials (CVOTs) are similar, differences in features such as enrollment criteria present a challenge when trying to assess the applicability of these studies to real-world T2D populations. This study evaluated the proportions of US adults with T2D who met the eligibility criteria for each of the 4 sodium-glucose cotransporter-2 (SGLT2) inhibitor CVOTs.

Study design: A cross-sectional retrospective study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) and published patient eligibility criteria for completed or ongoing SGLT2 inhibitor CVOTs.

Methods: Data on T2D diagnosis and other relevant clinical and demographic characteristics were extracted from the NHANES (2009-2010 and 2011-2012). Weighted analysis of these data was used to estimate the percentage of US adults with T2D who met the eligibility criteria for the CANVAS program (CANagliflozin cardioVascular Assessment Study) (canagliflozin; NCT01032629, NCT01989754), and the DECLARE-TIMI 58 (dapagliflozin; NCT01730534), EMPA-REG OUTCOME (empagliflozin; NCT01131676), and VERTIS-CV (ertugliflozin; NCT01986881) trials.

Results: The weighted analysis identified a population of 23,941,512 US adults from data on key inclusion criteria and information indicating a diagnosis of T2D. Of these, 4.1% met the criteria for EMPA-REG OUTCOME, 4.8% for VERTIS-CV, 8.8% for the CANVAS program, and 39.8% for the DECLARE-TIMI 58 trial.

Conclusions: There were considerable differences in the proportions of US adults with T2D who met the eligibility criteria for these studies.The DECLARE-TIMI 58 trial criteria were the most generalizable to the US T2D population.

MeSH terms

  • Benzhydryl Compounds / adverse effects
  • Benzhydryl Compounds / therapeutic use*
  • Canagliflozin / adverse effects
  • Canagliflozin / therapeutic use*
  • Cardiovascular Diseases / physiopathology*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Glucosides / adverse effects
  • Glucosides / therapeutic use*
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Sodium-Glucose Transporter 2 / metabolism
  • Sodium-Glucose Transporter 2 Inhibitors / adverse effects
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use*

Substances

  • 2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
  • Benzhydryl Compounds
  • Glucosides
  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • Canagliflozin

Associated data

  • ClinicalTrials.gov/NCT01032629
  • ClinicalTrials.gov/NCT01989754
  • ClinicalTrials.gov/NCT01730534
  • ClinicalTrials.gov/NCT01131676
  • ClinicalTrials.gov/NCT01986881