Dr Kevin Malloy Discusses the Evolution of GLP-1 Receptor Agonists

Kevin Malloy, PharmD, BCPS, BC-ADM, CDCES, Cleveland Clinic, presented on the history, current state, and future of GLP-1 receptor agonists in the management of diabetes at an Institute for Value-Based Medicine^® even hosted in partnership with the Cleveland Clinic.

As his presentation surveyed the development, use, and trajectory of this therapy, he joined The American Journal of Managed Care^® for an interview to discuss GLP-1 receptor agonists at length and the developments that have shaped their current use and understanding.

Transcript

How has the understanding of GLP-1 receptor agonists evolved, and what are some major milestones or breakthroughs that have shaped our understandings and informed the clinical uses of GLP-1 receptor agonists?

I think GLP-1 receptor agonists along with sodium glucose co-transporter 2—this SGLT2 inhibitor—these drug classes have really ushered in a change in how we manage diabetes, through food and through therapeutics. So you know, 10 years ago, treatment of diabetes with medications was really strictly looked at as glucose-lowering therapies. And using kind of whichever medications were needed and personalized to the patient with the pretty much sole goal of getting glucose concentrations, A1Cs to target, with sort of little regard to which agents may or may not provide better clinical outcomes when we're looking at reductions in the hard endpoints that we care about, which is reducing cardiometabolic endpoints. So cardiovascular disease in the form of a heart attack and ischemic stroke, cardiovascular death, chronic kidney disease, those really hard endpoints, which is ultimately what we're trying to reduce by controlling blood sugars, are yet to have agents that are specifically targeting or that have specifically shown independent of their glucose-lowering capabilities to reduce the risk of a lot of these endpoints.

And so really what we've shown, I think, with some of the initial cardiovascular outcome trials with GLP-1 receptor agonist—so the LEADER trial with liraglutide, SUSTAIN-6 with subcutaneous semaglutide; the REWIND trial with dulaglutide, which were really, you know, all published in really kind of a close period from 2016-2020, these really led to a new era in how our clinical practice guidelines are advocating for the use of specific drug classes. So, you know, in contrast to the ADA standards of care from 2016, which really just looked at using glucose-lowering therapies in a stepwise fashion and, when needed, insulin to get A1Cs and other glucose markers to target, we now are trying to preferentially use agents like GLP-1 receptor agonist in those patients with established or high cardiovascular risk before other agents. Even before metformin, which was kind of our tried and true first agent. Because we know that GLP-1receptor agonists are superior for these particular patients at lowering cardiovascular disease.

And then just an important second point, which is more of an evolving breakthrough, is that we have, of our newer GLP-1 receptor agonists, we have much—not only more effective glucose-lowering capabilities, but significantly more effective weight loss capabilities, which internally translates at a minimum to a reduction in cardiovascular surrogate markers: blood pressure, lipid profiles. These have really greatly emerged in the last 3, 4 or 5 years when we're really looking at diabetes. And even for those without high cardiovascular risk, per se, taking into context the majority of patients with type-2 diabetes in the United States who also have comorbid obesity, we're really trying to look at diabetes and treatment of type-2 diabetes through an obesity-centric management lens. I think that's one very large evolution in GLP-1 receptor agonists even in the last, you know, 4 or 5 years, that have really come on the coattails of some of the cardiovascular data that we've seen. They’ve significantly come a long way from just glucose-lowering therapies. So I think GLP-1s have really brought that into context and changed the lens at which we look at diabetes management.