Sodium-glucose co-transporter-2 inhibitor cardiovascular outcome trials and generalizability to English primary care.

W Hinton,N Munro,S Lusignan,M Feher,M Joy

doi:10.1111/dme.14290

Abstract

AimTo identify people in English primary care with equivalent cardiovascular risk to participants in the sodium–glucose co‐transporter‐2 inhibitor (SGLT‐2i) cardiovascular outcome trials (CVOTs). A secondary objective was to report the usage of SGLT‐2is.MethodsCross‐sectional analysis of people registered with participating practices in the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) network on the 31 December 2016. We derived: (1) proportions of the primary care population eligible for inclusion in each SGLT‐2i CVOT (CANVAS, DECLARE, EMPA‐REG and VERTIS); (2) characteristics of the eligible population compared with trial participants (demographics, disease duration and vascular risk); and (3) differences within the eligible population prescribed SGLT‐2is.ResultsThe proportions of people with type 2 diabetes (N = 84 394) meeting the inclusion criteria for each CVOT were: DECLARE 27% [95% confidence interval (CI) 26.5–27.1]; CANVAS 17% (16.6–17.1); VERTIS 7% (7.1–7.4); and EMPA‐REG 7% (6.5–6.8). Primary care populations fulfilling inclusion criteria were 5–8 years older than trial cohorts, and <10% with inclusion criteria of each trial were prescribed an SGLT‐2i; a greater proportion were men, and of white ethnicity.ConclusionsThere was variation in proportions of the primary care type 2 diabetes population fulfilling inclusion criteria of SGLT‐2i CVOTs. The more stringent the inclusion criteria, the lower the proportion identified in a primary care setting. Prescription rates for SGLT‐2is were low in this national database, and there were demographic disparities in prescribing.

Highlights

Cardiovascular outcome trials (CVOTs) are randomized controlled trials (RCTs) developed after 2008 following guidance from the US Food and Drug Administration (FDA) to ensure the cardiovascular safety of glucoselowering medications in type 2 diabetes [1]
The more stringent the inclusion criteria, the lower the proportion identified in a primary care setting
Using a national primary care database, we found that the inclusion criteria of four sodium– glucose co-transporter-2 (SGLT-2) inhibitor CVOTs applied to between 7% and 27% of people with type 2 diabetes

Summary

Introduction

Cardiovascular outcome trials (CVOTs) are randomized controlled trials (RCTs) developed after 2008 following guidance from the US Food and Drug Administration (FDA) to ensure the cardiovascular safety of glucoselowering medications in type 2 diabetes [1]. Cardiovascular superiority has been demonstrated in six CVOTs, with significant reductions for the primary composite endpoint for canagliflozin and empagliflozin from the sodium–glucose co-transporter-2 inhibitor (SGLT-2i) medication class, and liraglutide, albiglutide, semaglutide and dulaglutide, from the glucagon-like peptide-1 receptor agonist (GLP-1 RA) medication class [2,3,4,5,6,7] Generalizability of these trials to real-world type 2 diabetes populations is challenging because each trial had different inclusion criteria. A national primary care comparison of the first SGLT-2i CVOT, the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients– Removing Excess Glucose (EMPA-REG OUTCOME) trial, showed that only a small proportion of people with type 2 diabetes conformed to the trial inclusion criteria [8]. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK

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