New Antidiabetic Drugs in Cardiovascular Prevention in International Recommendations
Results from studies on new antidiabetic drugs showing cardiovascular (CV) benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i, gliflozins) and glucagon-like peptide 1 receptor agonists (GLP-1RA) have led to efforts to create new recommendations for their use in patients with type 2 diabetes mellitus (T2DM) for primary and secondary CV disease prevention. A recent review by American experts succinctly summarizes what current guidelines from American and European professional societies say on this subject.
ESC/EASD
The European Society of Cardiology and the European Association for the Study of Diabetes (ESC/EASD) in their 2019 guidelines recommend that patients with T2DM and known cardiovascular disease (CVD) or high risk of developing CVD should be treated with GLP-1RA or SGLT2i and that metformin should be administered only if there is still a need to compensate for hyperglycemia. The cardiovascular effects of GLP-1RA or SGLT2i are described as “largely independent of the glycemic lowering effect”. They note a reduction in the risk of hospitalizations for heart failure as an indication for SGLT2i, as well as their use in patients with chronic kidney disease (CKD) with eGFR 30 to < 90 ml/min/1.73m2. The guidelines state that thiazolidinediones and dipeptidyl peptidase 4 inhibitors (DPP-4i, gliptins) should not be given to patients with heart failure.1
AACE
The American Association of Clinical Endocrinologists (AACE) in their 2019 consensus recommends initiating treatment for patients with T2DM and known atherosclerotic CVD or high risk of developing such disease with long-acting GLP-1RA or SGLT2i with proven CV benefit. Administration of SGLT2i with proven benefit is also recommended for patients with moderate to severe CKD or heart failure with reduced ejection fraction (HFrEF), regardless of the presence of T2DM. The document states that SGLT2i reduce the risk of hospitalization for heart failure in patients with known CVD.1
ADA
The 2021 recommendations of the American Diabetes Association (ADA) suggest administering GLP-1RA and SGLT2i to reduce the risk of major adverse cardiovascular events (MACE), hospitalization for heart failure, CV mortality, or CKD progression in type 2 diabetics with atherosclerotic CVD, heart failure, or chronic kidney disease, regardless of glycated hemoglobin (HbA1c) levels, metformin use, and target HbA1c. However, they still recommend metformin as first-line treatment. For patients without the mentioned conditions, these drugs are recommended if HbA1c is not adequately controlled with metformin and lifestyle modifications.2
ACC/AHA
The American College of Cardiology (ACC) in their 2020 standards recommend considering the administration of GLP-1RA with proven CV benefit for patients with atherosclerotic CVD at the time of T2DM diagnosis, unless the patient is pregnant or breastfeeding, and administering SGLT2i with proven benefit for the said conditions in patients with atherosclerotic CVD, high risk of this disease, heart failure, or diabetic kidney disease, unless the patient is pregnant or has an eGFR < 30 ml/min/1.73 m2.3
The 2019 recommendations of the ACC and the American Heart Association (AHA) suggest in primary prevention for patients with T2DM and additional CV risk factors who need further antihyperglycemic therapy despite lifestyle modifications and metformin use, to consider GLP-1RA or SGLT2i to reduce CV risk.1
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Sources:
1. Bloomgarden Z., Handelsman Y. Management and prevention of cardiovascular disease for type 2 diabetes: integrating the diabetes management recommendations of AACE, ADA, EASD, AHA, ACC, and ESC. Am J Prev Cardiol 2020 May 1; 1: 100007, doi: 10.1016/j.ajpc.2020.100007.
2. American Diabetes Association. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes − 2021. Diabetes Care 2021 Jan; 44 (Suppl. 1): S111−S124, doi: 10.2337/dc21-S009.
3. Das S. R., Everett B. M., Birtcher K. K. et al. 2020 expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 2020 Sep 1; 76 (9): 1117−1145, doi: 10.1016/j.jacc.2020.05.037.
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