GLP-1 Agonists for the Treatment of Type 2 Diabetes - Episode 4
Vanita Aroda, MD: So 2019 was a great year in terms of new guidance and consensus guidance on the management of type 2 diabetes. If we look at the previous guidelines, they recommended getting patients to goal, keeping them at goal, and following A1C [glycated hemoglobin], and adding on therapy as needed to get people to goal.
But if you look at the previous guidelines, all of the therapies looked to be almost on an even plane. And what we’ve come to appreciate with a lot of randomized controlled trials, long-term studies, short-term studies, is that not all drugs have similar effect for all patients. So what we’ve seen for the first time with the 2019 guidance is true patient-centered guidelines, putting the patient at the center of the consideration of the choices of therapy. The big changes that we saw in the 2019 guidance included evaluating whether the patient has a history of cardiovascular disease. We now know from the randomized controlled trials that if someone has cardiovascular disease, certain therapies may have benefit compared to the other standards of care therapies. So that’s the first big change: Establishing whether a patient has a history of cardiovascular disease or cardiovascular risk. And in those patients, one would consider either a GLP-1 [glucagon-like peptide-1] receptor agonist or an SGLT2 [sodium-glucose cotransporter 2] inhibitor. And there are nuances in terms of when one might consider each of those.
The second big change that we saw in the 2019 guidance is earlier consideration of GLP-1 receptor agonists. Specifically, if someone is being considered for injectable therapy, GLP-1 receptor agonists should be considered even prior to insulin, unless there’s clear indication for insulin, such as a very high A1C, such as an A1C above 11%, or symptoms of severe insulin deficiency, like catabolic symptoms, weight loss, polyuria, polydipsia.
And this year we’ve seen a recognition based on the randomized control trial evidence that GLP-1 receptor agonists have a comparable, or even greater efficacy than insulin, without the weight gain and without the associated hypoglycemia. So they’ve moved up when considering injectable therapy. So those are the 2 big changes that I would say stand out with the 2019 guidance.
John B. Buse, MD, PhD: In October of 2018, the American Diabetes Association [ADA] and the European Association for the Study of Diabetes came together and developed a new version of the recommendations around management of hyperglycemia in type 2 diabetes. So the major focus is exactly that. This is what to do to manage high blood sugars in diabetes. And the things that are fundamentally new this time are a greater emphasis on weight management and lifestyle therapy, in general. We’ve always said that that was foundational in diabetes, but now we point out that there’s even more data that patients can have clinically meaningful weight loss with lifestyle management. And if that’s not enough, we have new medications that are effective. And if that’s not enough, bariatric surgery certainly plays a role. So that’s a greater emphasis based on the fact that we know that it can work. We have more and more evidence in that regard.
The second is a greater emphasis on so-called patient-centered shared decision making. And that’s the idea that in a chronic disease like diabetes, if we tell a patient what to do, there’s a 10% chance they’ll do it. I think all of us recognize in our lives that when our parents tried to tell us what to do and our bosses tried to tell us what to do, when anybody tries to tell us what to do in any realm, it’s hit and miss whether we actually do it in the long run. But if you engage in shared decision making, the patient is really participating in the process. I do think patients are generally adherent. They do what they agree to do when they participate in that decision.
And then the third and probably biggest change is an emphasis on what to do in patients with clinical cardiovascular disease. So we say that’s the first question you should ask a patient once you get past, “Tell me a bit about your life and why you are here today.” It’s absolutely essential that we understand whether patients have clinical cardiovascular disease or chronic kidney disease. And if they do, these 2 new classes of drugs, the SGLT2 inhibitors and the GLP-1 receptor agonist, have proven benefits for reducing events, heart attacks, stroke, bypass surgeries, interventions, heart failure hospitalizations, the progression of chronic kidney disease. These are really powerful, important endpoints.
Then the fourth thing that’s new, and probably the most controversial bit in the report, is the notion that if a patient needs the additional power of an injectable medication, they should actually turn to the GLP-1 receptor agonist first instead of insulin. And it’s very important that patients and providers understand whether they have type 1 or type 2 diabetes.
In type 1 diabetes, insulin is lifesaving. It’s absolutely essential. So for a patient with very high blood sugar, who’s losing weight and is very symptomatic, you should think about whether they might have type 1 diabetes, even if they’re 70 or 80 years old. So that thought has to go through your mind before you pull the trigger on prescribing a GLP-1 receptor agonist, but we recommended that class of drugs as the first injectable because they’re at least as powerful, with regard to A1C-lowering and improving blood sugar control, as insulin. But they do so with weight loss instead of weight gain, and with no risk of hypoglycemia, as opposed to a real risk of hypoglycemia with insulin. So those are the top-line recommendations from the American Diabetes Association now in 2019.
Vanita Aroda, MD: How close do providers and clinicians adhere to the guidelines? I would say that the guidelines are fairly impactful. But with any guidelines it takes time to see the actual uptake and incorporation, and to see a change in practice. So I think that it’s both an asset and a barrier. The nice thing is that the American Diabetes Association updates the standards of care every single year. So every January you see an assimilation and incorporation of recent evidence, and a really well thought-out guidance in terms of how clinical care standards might evolve and change. But it does take time to see it incorporated into day-to-day practice. We’ve seen plenty of publications on that front, whereby it could take a good 5 to 10 years before things become part of the day-to-day process.
John Anderson, MD: The ADA guidelines, along with the AACE [American Association of Clinical Endocrinologists] guidelines, are sort of a roadmap to help think about how you approach therapy in patients with type 2 diabetes. I think the American Diabetes Association guidelines are pretty well accepted. I think people understand the reasons behind it. And I do think most endocrinologists and primary care providers try to follow it. However, if we look at the real world, a lot of times we fall short of meeting those goals.
I firmly believe a lot of that’s cost. I think for a long time these agents were thought to be way too expensive. You know, 10 years ago, “Oh, nobody’s covering it.” Well if you look, in 2019, almost every commercial plan covers the GLP-1 receptor agonists, or an SGLT2 inhibitor. Almost every Medicare Part D plan covers 1 of those 2 classes of agents. So that old argument that cost drives everything is really not as true today as it used to be. Still, we do have some patients for whom cost is the number 1 factor, which is why we still see things like sulfonylureas and agents that are a lot less expensive but don’t provide the kind of benefit that we know these other classes do.
Transcript edited for clarity.