Dataset Information

How Generalizable Are Cardiovascular Outcome Trials of Sodium-Glucose Co-Transporter-2 Inhibitors? A National Database Study: Study Protocol.

ABSTRACT:

Introduction

Sodium-glucose co-transporter-2 (SGLT2) inhibitors are oral antihyperglycemic agents for the treatment of people with type 2 diabetes (T2DM). Two recent cardiovascular outcome trials (CVOTs), the EMPA-REG OUTCOME trial and CANVAS Program, have demonstrated that SGLT2 inhibitors have cardiovascular benefit in high-risk cardiovascular patients. The aim of our study will be to identify the prevalence of patients in an English primary care setting with the equivalent cardiovascular risk profile to those included in each of four SGLT2 inhibitor CVOTs: CANVAS, DECLARE, EMPA-REG, and VERTIS CV.

Methods

Routinely collected primary care data from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) network database will be used. We will perform a cross-sectional analysis to calculate the prevalence of people that have equivalent cardiovascular risk to participants included in each of the four above-mentioned SGLT2 inhibitor CVOTs. The demographic and clinical characteristics of the subgroups will also be compared with participants in each trial. The study cohort will include people with T2DM in the RCGP RSC dataset. Subgroups of people will be identified using Read codes that most closely match the inclusion criteria of each trial. Descriptive statistics will be used to report the characteristics of people at high cardiovascular risk and compared against those of people in each CVOT.

Planned outputs

Findings from the study will be submitted for publication in a peer-reviewed journal to report the applicability of each SGLT2 inhibitor trial to real-world clinical practice.

Funding

AstraZeneca UK Limited.

SUBMITTER: Hinton W

PROVIDER: S-EPMC6531500 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveTo compare the risk of cardiovascular events between sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors among people with type 2 diabetes in a real world context of clinical practice.DesignMulti-database retrospective cohort study using a prevalent new user design with subsequent meta-analysis.SettingCanadian Network for Observational Drug Effect Studies (CNODES), with administrative healthcare databases from seven Canadian provinces and the United Kingdom, 2013-18.Population209 867 new users of a SGLT2 inhibitor matched to 209 867 users of a DPP-4 inhibitor on time conditional propensity score and followed for a mean of 0.9 years.Main outcome measuresThe primary outcome was major adverse cardiovascular events (MACE, a composite of myocardial infarction, ischaemic stroke, or cardiovascular death). Secondary outcomes were the individual components of MACE, heart failure, and all cause mortality. Cox proportional hazards models were used to estimate site specific adjusted hazards ratios and 95% confidence intervals, comparing use of SGLT2 inhibitors with use of DPP-4 inhibitors in an as treated approach. Site specific results were pooled using random effects meta-analysis.ResultsCompared with DPP-4 inhibitors, SGLT2 inhibitors were associated with decreased risks of MACE (incidence rate per 1000 person years: 11.4 v 16.5; hazard ratio 0.76, 95% confidence interval 0.69 to 0.84), myocardial infarction (5.1 v 6.4; 0.82, 0.70 to 0.96), cardiovascular death (3.9 v 7.7; 0.60, 0.54 to 0.67), heart failure (3.1 v 7.7; 0.43, 0.37 to 0.51), and all cause mortality (8.7 v 17.3; 0.60, 0.54 to 0.67). SGLT2 inhibitors had more modest benefits for ischaemic stroke (2.6 v 3.5; 0.85, 0.72 to 1.01). Similar benefits for MACE were observed with canagliflozin (0.79, 0.66 to 0.94), dapagliflozin (0.73, 0.63 to 0.85), and empagliflozin (0.77, 0.68 to 0.87).ConclusionsIn this large observational study conducted in a real world clinical practice context, the short term use of SGLT2 inhibitors was associated with a decreased risk of cardiovascular events compared with the use of DPP-4 inhibitors.Trial registrationClinicalTrials.gov NCT03939624.

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