Mikhail N. Kosiborod
CHICAGO —A speaker at the American Heart Association Scientific Sessions called on cardiologists to become more involved in the use of SGLT2 inhibitors and GLP-1 receptor agonists in patients with type 2 diabetes, as these glucose-lowering medications have been shown to improve CV outcomes in this population.
According to previous research published in the Journal of the American College of Cardiology, cardiologists prescribed only about 5% of all SGLT2 inhibitors from 2013 to 2017, with no appreciable increase after the FDA expanded labeling for use of these agents for CV risk reduction.
“We have a fundamental paradigm shift in type 2 diabetes management,” Mikhail N. Kosiborod, MD, professor of medicine at Saint Luke’s Mid America Heart Institute and the University of Missouri-Kansas City, said during his presentation. “There are several classes of glucose-lowering medications that were developed for glucose lowering but now have been shown to improve CV outcomes with highly favorable benefit-risk balance and [with] CV outcomes likely not being related to its glucose-lowering properties.”
SGLT2 inhibitors have consistently shown to prevent HF and the progression of renal disease, according to Kosiborod. Meanwhile, the strongest benefits of GLP-2 receptor agonists (RAs) are their effect on major CV events and arteriosclerotic disease progression.
“These emerging data should shift the focus of type 2 diabetes to comprehensive risk reduction, and cardiologists need to take a more active role,” Kosiborod said.
He noted an “avalanche of positive data for the class” of SGLT2 inhibitors. Findings from the EMPA-REG, CANVAS and DECLARE-TIMI 58 trials demonstrated consistent and significant reductions in hospitalization for HF and progression of kidney disease that was “unequivocal and highly consistent with all three agents across all three classes.” However, DECLARE-TIMI 58 indicated a higher risk for genital mycotic infections with the SGLT2 inhibitor dapagliflozin compared with placebo. Kosiborod said the trial found a statistically significant lower risk for acute kidney injury, and lower risks of bladder cancer and necrotizing fasciitis with dapagliflozin vs. placebo.
“Overall on the safety side, things look extremely favorable, and certainly [there is a] favorable benefit-risk balance,” he said.
Kosiborod’s review of data from ELIXA, LEADER, SUSTAIN-6, EXSCEL, HARMONY and REWIND indicated that GLP-1 RAs as a class showed “a consistent and significant reduction of three-point MACE.”
“The offset is a higher risk of nausea,” he said. “All of these other things that were potential concerns when these agents were developed — hypoglycemia, pancreatitis and pancreatic cancer — are really not panning out in any of the trials. If you look at all the totality of data, there is really no evidence that these are substantial concerns.”
Despite data on these two classes of agents showing an impact on CV endpoints, Kosiborod said cardiologists are “sitting on the sidelines” and have the lowest prescribing patterns for these therapies. He also said cardiologists have a responsibility to learn about the approval of and reimbursement strategies for agents that reduce CV events. He noted the injectables are easy to use and feasible for patients to self-administer. Cardiologists who worry about management of non-CV diabetes-related issues can collaborate with colleagues from other specialties.
“The main reason I think cardiologists stayed on the sidelines is this question: Why bother? I would say the argument that we have no data that intervening with any glycose-lowering medication has a significant impact on CV outcomes is clearly gone now,” he said. “So, we really need to start paying attention and get involved.” – by Gina Brockenbrough, MA
Kosiborod MN. Role of newer anti-diabetic drugs to reduce CV risk. Presented at: American Heart Association Scientific Sessions; Nov. 10-12, 2018; Chicago.
Vaduganathan M, et al. J Am Coll Cardiol. 2018;doi:10.1016/j.jacc.2018.08.2202.
Disclosure: Kosiborod reports being a consultant and serving on the advisory board for Amgen, AstraZeneca, Boehringer Ingelheim, Eisai, GlaxoSmithKline, Glytec, Intarcia, Janssen, Merck, Novo Nordisk and Sanofi Pasteur; receives research grants or support from AstraZeneca and Boehringer Ingelheim; and receives honoraria from AstraZeneca, Boehringer Ingelheim and Novo Nordisk.