The latest update to international guidance for the management of type 2 diabetes recommends the use of GLP-1 receptor agonists or SGLT2 inhibitors to reduce the risk of cardiovascular events and chronic kidney disease, irrespective of baseline glucose levels.
The American Diabetes Association and the European Association for the Study of Diabetes (ADA/EASD) have updated their 2018 consensus report based on findings from large cardiovascular outcome trials published during 2019.
New recommendations include:
- The decision to treat high-risk patients with a GLP-1 RA or SGLT2 inhibitor to reduce major cardiovascular events (MACE), hospitalisation for heart failure (hHF), cardiovascular death, or chronic kidney disease (CKD) progression should be considered irrespective of baseline HbA1c or individual HbA1c target.
- GLP-1 RAs can also be considered in patients with type 2 diabetes without established CVD but with the presence of specific indicators of high risk.
- SGLT2 inhibitors are recommended in patients with type 2 diabetes and heart failure, particularly those with heart failure with reduced ejection fraction, to reduce hHF, MACE and CVD death, as well as in patients with type 2 diabetes with CKD (eGFR rate 30 to ≤60 ml/min/1.73m2 or urinary albumin-to-creatinine ratio >3 mg/mmol, and particularly >30 mg/mmol) to prevent the progression of CKD, hHF, MACE and cardiovascular death.*
Based on studies published to date, the ADA/EASD considers that for patients with type 2 diabetes and established atherosclerotic CVD (prior myocardial infarction, ischaemic stroke, unstable angina with ECG changes etc) where MACE is the gravest threat, the level of evidence for MACE benefit is greatest for GLP-1 RAs.
For patients with or without established atherosclerotic CVD, but with heart failure with reduced ejection fraction or CKD, defined above, the level of evidence is greatest for SGLT2 inhibitors.
In the 2018 report, the ADA/EASD said it had found no evidence of advantage for using initial combination therapy for newly diagnosed patients, but a recent study of vildagliptin in combination with metformin for the early treatment of type 2 diabetes (VERIFY) showed that using this combination of a DPP-4 inhibitor and metformin resulted in a lower rate of failure of glycaemic control than using these drugs sequentially. Therefore, the ADA/EASD now suggests considering initial combination therapy in new onset cases of type 2 diabetes.
The report concludes that while the way that GLP-1 RAs and SGLT2 inhibitors confer cardiovascular and renal benefits is not yet understood, there is now clear potential of drugs for diabetes to reduce the cardiovascular and renal complications of the disease.
*Many of these recommendations are outside the current product licenses for GLP-1 RAs and/or SGLT2 inhibitors. Clinicians should consult the summary of product characteristics before prescribing, or follow the advice on off-label prescribing at https://www.gov.uk/drug-safety-update/off-label-or-unlicensed-use-of-medicines-prescribers-responsibilities
Buse JB, et al. Diabetes Care 2019 Dec; dci190066. https://care.diabetesjournals.org/content/early/2019/12/18/dci19-0066