Two cardiologists faced off in a virtual debate examining whether sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists should have a more prominent role in cardiovascular interventions on Monday, June 15, during the Scientific Sessions.
Mikhail Kosiborod, MD, Professor of Medicine at Saint Luke’s Mid America Heart Institute, University of Missouri-Kansas City, argued that SGLT2 inhibitors and GLP-1 receptor agonists should be used for primary cardiovascular disease (CVD) prevention during the session, Debate—Primary Cardiovascular Prevention with SGLT2 Inhibitors or GLP-1 Receptor Agonists—Are We Ready for Prime Time? The debate can be viewed by registered meeting attendees at ADA2020.org through early September.
Dr. Kosiborod said there is no physiologic reason a preventative therapy would work only in secondary prevention and not primary prevention, which was disputed by Darren K. McGuire, MD, MHSc, Distinguished Teaching Professor of Medicine at the University of Texas Southwestern Medical Center.
“Prevention doesn’t equal treatment,” Dr. McGuire said. “And that’s in the field of oncology, in antibiotics for infections—there are times when you wouldn’t use a drug that’s proven to treat a disease to prevent a disease.”
Dr. McGuire contends the readiness of SGLT2 inhibitors and GLP-1 receptor agonists is muddied by the generic “cardiovascular disease” label.
“The implication in most of these conversations, in the regulatory guidance, and in the randomized trial design and outcomes of every trial we’ve done in this space is atherosclerosis,” Dr. McGuire said. “So in this space when people say CVD, they mean atherosclerotic cardiovascular disease (ASCVD). But, of course, there’s lots of other cardiovascular diseases.”
Indeed, Dr. Kosiborod shared examples of the efficacy of SGLT2 inhibitors and GLP-1 receptor agonists in preventing morbid cardiovascular events in patients with and without ASCVD.
“This is supported by label indications and practice guidelines. It’s not just my opinion,” said Dr. Kosiborod, citing the U.S. Food and Drug Administration’s approval of dapagliflozin to reduce hospitalization for heart failure and dulaglutide to reduce major adverse cardiovascular events (MACE) in adults with type 2 diabetes and established cardiovascular disease or multiple cardiovascular risk factors.
The efficacy of SGLT2 inhibitors and GLP-1 receptor agonists makes “the juice worth the squeeze” when it comes to cardiovascular prevention therapy, Dr. Kosiborod contends. If large populations at risk for type 2 diabetes are treated with these drugs, a very large number of MACE and heart failure hospitalizations will likely be avoided, he said.
Dr. McGuire questioned the cost-effectiveness of this approach.
Based on data from the Researching Cardiovascular Events With a Weekly Incretin in Diabetes (REWIND) trial showing an absolute risk difference of 0.3%, the number of patients needed to treat with no prior cardiovascular disease is 333, Dr. McGuire explained. Using pricing found online, he calculated $3.4 million in drug costs would be needed to prevent a single MACE.
“It’s hard to convince me that this juice is worth this squeeze,” he said.
But cost is a constantly shifting parameter, Dr. Kosiborod pointed out. And although some SGLT2 inhibitors and GLP1 receptor agonists are on track to become generic and, therefore, much less expensive in the foreseeable future, he said the need for them exists now.
Dr. Kosiborod shared 2019 data from a registry of 120 U.S. medical centers looking at optimal medical therapy for people with type 2 diabetes who already have established ASCVD that showed less than 7% of patients in a secondary intervention cohort are receiving optimal, guideline-directed medical therapy. For him, this underscores the need for SGLT2 inhibitors and GLP1 receptor agonists in primary cardiovascular prevention.
“Given the burgeoning number of individuals with type 2 diabetes and clinical inertia, the time to start implementation is now,” Dr. Kosiborod concluded. “We should not be waiting.”
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