Adequately treating diabetes demands an array of considerations and therapy strategies.
Yehuda Handelsman, MD, FACP, FNLA, FASPC, MACE: The contemporary approach to managing diabetes is not only to control hyperglycemia but also to truly prevent the next event and protect the patient from complications. Jennifer, do you want to start?
Jennifer B. Green, MD: Yes, I’d be happy to do that. Think about the ADA [American Diabetes Association] algorithm for the choice of pharmacological agents to manage hyperglycemia in type 2 diabetes, or the even newer iteration—a joint ADA/EASD [European Association for the study of Diabetes] algorithm. It’s very clear that there’s a bit of a dichotomy with the left side of that algorithm focused on the individual who has established atherosclerotic cardiovascular disease [ASCVD] or has multiple risk factors for ASCVD, has heart failure, or has evidence of kidney disease. There are very specific recommendations for the incorporation of particular agents into the care of those individuals because those agents have shown the ability to significantly reduce the risk of cardiovascular and kidney outcomes in those populations.
Another important change that’s sometimes difficult for individuals to appreciate from that algorithm is that it’s very important, to include those medications in the care of the individual, regardless of whether they need additional glucose lowering or if they’re already on metformin. For example, if a person who’s had a prior MI [myocardial infarction] is subsequently diagnosed with type 2 diabetes, then you can use [medications] from the outset. It would be very reasonable and perhaps even a preferred approach to start with these newer beneficial medications right off the bat.
In a nutshell, that’s the way we’re seeing care emerge. There are separate considerations for the “lower-risk person” with diabetes who’s focused simultaneously on glucose control and weight management, which are closely linked from a pathophysiological perspective. But we care about those things for the higher-risk patients too. There’s a lot to think about, but we have much better tools to help reduce the risk of these serious complications in our patients even if they’ve had diabetes for extended periods of time.
Yehuda Handelsman, MD, FACP, FNLA, FASPC, MACE: Eugene Braunwald, the most revered cardiologist alive, said SGLT2 inhibitors today are [like what] statins [were in] the 1990s. What do you think?
Eugene E. Wright Jr, MD: They certainly have the potential to do a lot of things in 1 class of medication that will touch lots of patients with diabetes. We talked about glucose lowering. We’ve talked about cardiovascular protection, heart failure, and kidneys. There’s a lot to be said about that. They operate in a way other than lowering blood glucose. I like that concept, but from a primary care perspective, it’s much more fun to think about preventing disease than treating illness. We certainly do that. We see lots of patients that come to us across the spectrum. It’s hard to take care of individuals who are at the end of cardiovascular disease, renal disease, or diabetes. We have tools. We have better tools than we had 5 or 10 years ago, but that requires a lot of effort. It’s much more fun, for the patient and the practitioner, to try to prevent these complications.
Jennifer B. Green, MD: That’s true. We need to think about the cost in making those decisions. The absolute benefit or reduction in risk with these newer agents is more clearly evident in individuals who are at higher risk with more advanced complications. However, it’s clear that treating individuals with diabetes earlier with these medications can also reduce risk in the person, for example, with multiple risk factors but not established disease. But you probably need to treat more individuals for a longer period of time to reduce the same number of events as you would in the high-risk population.
Yehuda Handelsman, MD, FACP, FNLA, FASPC, MACE: You can see how we’re prisoners of randomized control trials and the way pharmaceutical companies go about it. It’s always funny that we have to disclose our relationship to a pharmaceutical [company], but when we use grade A pharmaceutical studies, they’re out. There’s a dichotomy. In my mind, various regulators are a conflict of interest. However, they have 1 thing on their minds: getting the drug on the market as soon as they can. Therefore, various studies have shorter effects. Because of that, if you take somebody at higher risk with established cardiovascular disease, then you see the effects in 2 to 25 years and you get it onto the market. What happens to patients earlier? With GLP1 receptor agonists, we’ve seen in some of the studies that individuals who were at higher risk were better. With SGLT2 inhibitors, they also exist but the data is only for 2½ years, so it’s not as clear as it is with the individuals with a GLP1 receptor.
In EMPEROR-Preserved, I believe there are data to show an improvement in 18 days. In EMPEROR-Reduced, evidence shows an improvement in 12 days. These very early improvements are important. With regional studies, you start to see separation in whether individuals with established or unestablished disease have to start early on. How long are they in the study to get a statistically significant improvement? I’m with you. I want to give it early. I want to give it in combination. I want to prevent what’s going on because I know my patient has diabetes. Jaime [Murillo] just said age 36, right? Age 36, type 1 [diabetes]. We used to say patients with type 1 [diabetes] didn’t have cardiovascular disease. Age 36—this means you need to start managing them at age 25. You need to start treatment way before age 40. Here we are. It’s a big contention going on. When we’re looking at the GLP1 and SGLT2 inhibitors, there’s a new set. The data show that independent of glucose and other medication, they will get patients to their goal. Patients come to me on a diet with an A1C [glycated hemoglobin] level of 6.4%, with some heart problem. I’ll start the medication, but not metformin at that point.
Transcript edited for clarity.
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