AMSTERDAM – The era of guidelines that recommended treatment with either a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or a glucagonlike peptide-1 (GLP-1) receptor agonist in people with mellitus and established cardiovascular disease (CVD) ended with new recommendations from the European Society of Cardiology that call for starting both classes simultaneously.
said Darren K. McGuire, MD, at the annual congress of the European Society of Cardiology.
The society’s new, released on Aug. 25 and presented in several sessions at the Congress, also break with the past by calling for starting treatment with both an SGLT-2 inhibitor and a GLP-1 receptor agonist without regard to a person’s existing level of glucose control, including their current and target hemoglobin A1c levels, and regardless of background therapy, added Dr. McGuire, a cardiologist and professor at the UT Southwestern Medical Center in Dallas and a member of the ESC panel that wrote the new guidelines.
Instead, the new guidance calls for starting both drug classes promptly in people diagnosed with type 2 diabetes and established atherosclerotic CVD.
Different mechanisms mean additive benefits
“With increasing numbers of patients with type 2 diabetes in trials for SGLT-2 inhibitors or GLP-1 receptor agonists who were also on the other drug class, we’ve done large, stratified analyses that suggest no treatment-effect modification” when people received agents from both drug classes, Dr. McGuire explained in an interview. “While we don’t understand the mechanisms of action of these drugs for CVD, we’ve become very confident that they use different mechanisms” that appear to have at least partially additive effects.
“Their benefits for CVD risk reduction are completely independent of their glucose effects. They are cardiology drugs,” Dr. McGuire added.
The new ESC guidelines highlight two other clinical settings where people with type 2 diabetes should receive an SGLT-2 inhibitor regardless of their existing level of glucose control and any other medical treatment: people withand people with (CKD) based on a depressed estimated glomerular filtration rate and an elevated urine albumin-to-creatinine ratio.
Nephropathy was considered by the ESC’s guideline panel to confer risk that is similar to that of established atherosclerotic CVD, Dr. McGuire said.
The guidelines also, for the first time for ESC recommendations, made treatment with finerenone (Kerendia, Bayer) a class 1 level A recommendation for people with type 2 diabetes and CKD.
SCORE2-Diabetes risk estimator
Another major change in the new ESC guideline revision is introduction of a CVD risk calculator intended to estimate the risk among people with type 2 diabetes but without established CVD, heart failure, or CKD.
Called the, it calculates a person’s 10-year risk for CVD and includes adjustment based on the European region where a person lives; it also tallies different risk levels for women and for men.
The researchers who developed the SCORE2-Diabetes calculator used data from nearly 230,000 people to devise the tool and then validated it with data from an additional 217,000 Europeans with type 2 diabetes.
Key features of the calculator include its use of routinely collected clinical values, such as age, sex, systolic blood pressure, smoking status, serum cholesterol levels, age at diabetes diagnosis, hemoglobin A1c level, and estimated glomerular filtration rate.
“For the first time we have a clear score to categorize risk” in people with type 2 diabetes and identify who needs more aggressive treatment to prevent CVD development,” said Emanuele Di Angelantonio, MD, PhD, deputy director of the cardiovascular epidemiology unit at the University of Cambridge (England).
The guidelines say that people who have a low (< 5%) or moderate (5%-9%) 10-year risk for CVD are possible candidates fortreatment. Those with high (10%-19%) or very high (≥ 20%) risk are possible candidates for treatment with metformin and/or an SGLT-2 inhibitor and/or a GLP-1 receptor agonist, said Dr. Di Angelantonio during his talk at the congress on the new risk score.
“The risk score is a good addition” because it estimates future CVD risk better and more systematically than usual practice, which generally relies on no systematic tool, said Naveed Sattar, PhD, professor of metabolic medicine at the University of Glasgow (Scotland) and also a member of the guideline-writing panel.
The new risk score “is a reasonable way” to identify people without CVD but at elevated risk who might benefit from treatment with a relatively expensive drug, such as an SGLT-2 inhibitor, Dr. Sattar said in an interview. “It doesn’t rely on any fancy biomarkers or imaging, and it takes about 30 seconds to calculate. It’s not perfect, but it gets the job done,” and it will increase the number of people with type 2 diabetes who will receive an SGLT-2 inhibitor, he predicted.
Dr. McGuire has been a consultant to Altimmune, Applied Therapeutics, AstraZeneca, Bayer, Boehringer-Ingelheim, Intercept, Lexion, Lilly, Merck, New Amsterdam, and Pfizer. Dr. Di Angelantonio had no disclosures. Dr. Sattar has been a consultant to Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk, Pfizer, and Roche Diagnostics.
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