ACC offers guidance on using diabetes drugs for CV event reduction

A new expert consensus document from the American College of Cardiology singled out liraglutide and empagliflozin as the preferred drugs in their classes to reduce cardiovascular risk among patients with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD).

Published online Nov. 26, the paper represents a paradigm shift for how cardiovascular specialists should care for their patients with type 2 diabetes (T2D), according to the writing committee. This is because recent evidence has demonstrated significant reductions in cardiovascular events associated with certain sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1RAs).

“Previously, CV care in patients with diabetes was centered around risk factor optimization, and the medications used for glycemic control were not expected to demonstrate direct CV benefit,” wrote the multidisciplinary writing committee, which was co-chaired by Sandeep R. Das, MD, MPH, and Brendan M. Everett, MD, MPH. “The recent development of 2 novel classes of therapies—SGLT2 inhibitors and GLP-1RAs—has, for the first time, demonstrated that treatments developed for glucose lowering can directly improve CV outcomes.”

The authors noted the CVD risk reduction appears to be independent of the A1c-lowering capabilities of the drugs, making it necessary for cardiologists to work more closely with other specialists to optimize CV outcomes for this high-risk population and to take a more active role in prescribing these medications.

Das, Everett and colleagues said empagliflozin should the preferred SGLT2 inhibitor based upon the current evidence. In the EMPA-REG OUTCOME trial, patients randomized to that drug instead of a placebo experienced a 14 percent reduction in the combined endpoint of cardiovascular death, MI or stroke. They also showed a 32 percent reduction in all-cause mortality and a 38 percent reduction in cardiovascular death, leading to an FDA indication to reduce the risk of cardiovascular death in adults with T2D and established CVD.

“Because there is no evidence of a graded dose response regarding CV disease outcomes, SGLT2 inhibitors with demonstrated CV benefit should be initiated at the lowest available dose (e.g., 10 mg for empagliflozin, 100 mg for canagliflozin, and so on),” Das et al. wrote. “No further up-titration is needed for CV risk reduction, although dose may be increased by the doctor managing the patient’s glucose, and cardiologists should make patients aware that this may happen for non-CVD risk reduction reasons.”

When it comes to GLP-1RAs, liraglutide has “the most convincing data for CV benefit,” the authors said. In the LEADER trial, liraglutide was associated with a 13 percent reduction in stroke, MI and cardiovascular mortality compared to placebo, and a 15 percent reduction in all-cause mortality. The goal dose for CVD reduction is 1.8 mg daily of liraglutide.

The panel recommended clinicians explain to patients the potential side effects, drug-drug interactions and costs of these newer medications, because both classes of drugs are expensive and could lead to “considerable” out-of-pocket costs. They said discussions about these therapies should take place with people who have T2D and clinical ASCVD either when one of those conditions is newly diagnosed, or during a follow-up visit when both diseases are already established.

When it comes to choosing one drug class versus the other, Das and coauthors said the route of administration (oral for SGLT2 inhibitors, subcutaneous for GLP-1RA), insurance coverage and comorbidities could weigh into the decision-making. For now, the authors believe patients with heart failure or at high risk of heart failure may be better off with SGLT2 inhibitors, while those with osteoporosis, amputations, severe peripheral artery disease or peripheral neuropathy might have “a more favorable benefit/risk balance if initially treated with a GLP-1RA.”

Nevertheless, ongoing cardiovascular outcomes trials for T2D patients may cause these recommendations to be tweaked, Das et al. acknowledged—but the goals of treatment will remain the same.

“Ultimately, the main goals of care for these high-risk patients should be improving survival and quality of life. … If used appropriately, the SGLT2 inhibitors and GLP-1RAs discussed in this document should significantly reduce CV morbidity and mortality in these patients,” the authors wrote.