Five advancements in diabetes treatment to watch
3. Medications to treat both diabetes and cardiovascular disease
For the first time, medical evidence supports a cardiovascular risk reduction treatment associated with some anti-diabetic therapies: two GLP-1 receptor agonists—liraglutide (currently available) and semaglutide (began the FDA approval process in December 2016), and one SGLT-2 transport inhibitor—empagliflozin.
“These cardiovascular outcomes trials were published in 2015 and 2016 and were groundbreaking,” Pantalone says. “For the first time, some diabetes drugs were demonstrated to have an effect beyond simply lowering blood sugar levels. This is very important, as cardiovascular disease is the number one cause of death in patients with diabetes type 2. If a therapy can lower blood sugar levels and simultaneously potentially lower a patient’s risk of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke, it would be preferred to use these therapies in patients considered high risk (those with established cardiovascular disease or those with numerous risk factors for cardiovascular disease).”
In a clinical study published in The New England Journal of Medicine using the SGLT-2 inhibitor empagliflozin in type 2 diabetes patients with pre-existing heart disease, researchers reported a 38% risk reduction in cardiovascular death and a 35% risk reduction in heart failure hospital admissions. No significant reduction in heart attack or stroke was noted, however.
“Mechanistically, this continues to be explored, but it is the first drug class with well-managed modern background therapy in diabetes to show total mortality reductions,” says Curtis Triplitt, PharmD, associate professor of medicine, University of Texas Health Science Center at San Antonio. “Whether all type 2 diabetes cardiovascular patients should receive empagliflozin is currently being debated.”
In another clinical trial published in The New England Journal of Medicine, liraglutide, a GLP-1 receptor agonist, reported a 15% reduction in all-cause mortality, but most relate this to a cumulative effect of reductions from heart attack and strokes, Triplitt says. Upon further analysis, patients who took the drug as prescribed received the cardiovascular benefit. Both empagliflozin and liraglutide also reported improvements in renal outcomes; further strengthening their potential use in therapy.
The cardiovascular outcome trials of the remaining FDA-approved GLP-1RA (exenatide once weekly, albiglutide, and dulaglutide), and the other SGLT-2 transport inhibitors (canagliflozin and dapagliflozin) are still in progress and should conclude over the next few years. “If these studies find similar results, that would be something to watch, as we can then say that the observed cardiovascular risk reduction is actually a class effect, and not specific to just a few agents within the class,” Pantalone says.