Table 2.

Current recommendations based on CVOTs for patients with established CVD or at high risk for CVD

Guidelines	Selected recommendations for CVD management based on diabetes CVOTs
ADA 2022	For patients with T2D who have established ASCVD or high / very high CV risk, SGLT2 inhibitors or GLP-1 RA with proven cardiovascular benefit are recommended as part of glycaemic management:* • Either a GLP-1 RA with proven CVD benefit or an SGLT2 inhibitor with proven CVD benefit • If further intensification is required or the patient is now unable to tolerate a GLP-1 RA and/or SGLT2 inhibitor choose agents demonstrating CV safety; consider adding the other class (GLP-1 RA or SGLT2 inhibitor) with proven CVD benefit†
ACC 2020	For patients with T2D who have established or high risk of ASCVD consider an SGLT2 inhibitor or GLP-1 RA with proven CV benefit
ADA and EASD 2019	For patients with T2D who have established ASCVD, an SGLT2 inhibitor or GLP-1 RA with proven cardiovascular benefit is recommended as part of glycaemic management: • First-line therapy is metformin • Add an GLP-1 RA with proven CVD benefit or, if eGFR is adequate, an SGLT2 inhibitor with proven CVD benefit • If further intensification is required or the patient is now unable to tolerate a GLP-1 RA and/or SGLT2 inhibitor, choose agents demonstrating CV safety†
ESC (in association with EASD) 2019	Consider CV risk independently of Hb1Ac; for patients with T2D who have ASCVD, or high/very high CV risk (target organ damage or multiple risk factors) • SGLT2 inhibitor or GLP-1 RA (either as first add-on to metformin or as monotherapy; however, drug labels stipulate that metformin should be first line) • If HbA1c is above target, consider adding the other class (GLP-1 RA or SGLT2i) with proven CVD benefit

A summary of recommendations in major international guidelines that are based on evidence from diabetes CVOTs. These guidelines include the American Diabetes Association (ADA) Standards of Medical Care in Diabetes 2022 [44]; American College of Cardiology (ACC) 2020 Expert Consensus Decision Pathway on Novel Therapies for Cardiovascular Risk Reduction in Patients with Type 2 Diabetes and Atherosclerotic Cardiovascular Disease [39]; Management of hyperglycaemia in type 2 diabetes, 2018: A consensus report by the ADA and the European Association for the Study of Diabetes (EASD), together with its 2019 update [40, 42]; 2019 European Society of Cardiology (ESC) Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD [38]

ASCVD, atherosclerotic cardiovascular disease; CV, cardiovascular; CVD, cardiovascular disease; CVOT, cardiovascular outcomes trial; GLP-1 RA, glucagon-like peptide-1 receptor agonist; Hb1Ac, haemoglobin A1c; SGLT2, sodium–glucose transporter 2

*Other options are thiazolidinediones, DPP-4 inhibitors if not on GLP RA, basal insulin, sulfonylureas

^†Based on the flowchart of treatment of patients with T2D in the ADA 2022 guidelines, “first-line therapy depends on comorbidities, patient-centred treatment factors, including cost and access considerations, and management needs and generally includes metformin and comprehensive lifestyle modification”, and treatment choices are subsequently shown on the flowchart according to the presence/absence of ASCVD, indicators of high risk, heart failure, and chronic kidney disease