Navigating the Evidence: From Clinical Trial to Clinical Practice

Dennis P. Scanlon, PhD: I want to move this discussion to a discussion about targeting treatments to specific patients. We’ve talked a lot about team-based care, but as we look at the evidence and we look at new therapeutic treatments that have come out, taking a patient-centered approach in diabetes care means looking at many available treatment options—SGLT2s (sodium-glucose cotransporter-2 inhibitors), and the TZDs (thiazolidinediones), and so forth. We might start with metformin, but how do we know where to go from there? How does a provider approach that decision?

Robert Gabbay, MD, PhD, FACP: I think we all probably have different ways.

Robert Gabbay, MD, PhD, FACP: I think one of the challenges is, there aren’t large studies that say that in somebody on metformin, what the best next agent is. We really have to base our decisions on the fact that each of the medicines work in different ways. They have added benefits beyond just glucose control—whether that’s weight loss, less hypoglycemia. Ultimately, it’s a negotiation and a shared-decision process with patients of what’s most important to them. Is it the cost of the medicine? Is it weight loss? Is it the risk of hypoglycemia? And, based on that and their comorbidities, choosing the right agent.

John A. Johnson, MD, MBA: I’d add 2 more factors. First being the presentation of the patient at the time of diagnosis. Some diabetics, again, are very symptomatic and severe such that an oral agent at the start may not be the right approach. But then, secondly, on the managed care side, you’ve got to consider the formulary of the member or the patient that you’re treating.

Zachary T. Bloomgarden, MD, MACE: Right. The dilemma is that we now have very powerful medicines which really have the same glycemic benefit for people who are fairly high in blood sugar—SGLT2 inhibitors, GLP-1 (glucagon-like peptide-1) receptor agonists. There are large head-to-head trials which look at, let’s say insulin glargine versus a GLP-1 drug, showing that you get less weight gain, less hypoglycemia, and equivalent or even better glycemic control with GLP-1s as compared to insulin glargine. Quite an impressive outcome. Yet, many managed care formularies will actually tell us that before using the GLP-1 drug, you have to do this, and this, and this, and this—steps that have no real medical basis other than cost consideration.

And cost is important, but we have to think that the acquisition cost of the drug is only a part. What really is expensive is the outcome. Sulfonylureas are widely used. Yet, there are these managed care databases that have been [evaluated], not so much in the United States, but in Europe and the United Kingdom, suggesting that individuals receiving metformin, and then a sulfonylurea, have higher mortality [rates] and higher cardiovascular disease outcome rates than individuals who have a DPP-4 (dipeptidyl peptidase-4) inhibitor added.

A similar study recently came out from a United States Veterans Administration database showing that thiazolidinediones lead to better outcomes than sulfonylureas when added to metformin. So, we’re starting to get this data, and yet, it hasn’t gotten to the formulary level. It has to because that will be so important in partnering with managed care when helping physicians appropriately treat their patients.

John A. Johnson, MD, MBA: I can’t speak for all of the managed care companies, but, at WellCare, we do make an attempt to make the most cost-effective agent in the different classes available to our members. There’s justification to say, “There’s an exclusion and you need to take an alternate path.” And with the documentation, we’ve had no issues with approving that. So, again, the important thing is the medications are tools. When you’re operating in the government-sponsored space, you want to make sure that you’re stewards of the state and the federal government’s money—using that wisely to make available to our members the most cost-effective agents.

Michael Gardner, MD: I don’t think you can lay this entirely at the feet of the managed care organizations and the insurance companies. Some of these medications are priced in ways that don’t make sense. Look at how much insulin has gone up over the last few years [in price]. Not just the name brands, but even the NPH (neutral protamine Hagedorn) insulin and the mixed insulins have gone up over the last few years. It doesn’t make sense.

Dennis P. Scanlon, PhD: We’ve seen that with the PCKS9s (proprotein convertase subtilisin kexin-9 inhibitors) in terms of pricing and there’s some therapeutic value—but for particular patients. Navigating that area in terms of formulary has been a big area of discussion.

John A. Johnson, MD, MBA: Yeah. And again, although none of us want to admit it, there are some clinicians that start with the agents they were trained with, or, which may not be the most cost-effective. The managed care steps in to say, “Let’s make sure that there’s a method and that there’s a step approach.” Where there are exclusions, or medication that’s inappropriate for a patient, they need to make that information available to the health plan. You shouldn’t have a problem getting it approved.

Michael Gardner, MD: Sometimes we don’t consider the total cost. The total cost of a sulfonylurea is probably far higher than the $4.00 [price at] Walmart reflects. Is it the cost of the hospitalization that results from the hypoglycemia? Or the hip repair? Because you’ve got hypoglycemia, you fell and broke your hip and now you need an expensive orthopedic procedure. I know that it’s difficult because one who may be on WellCare this year, may be on some other plan the next year.

John A. Johnson, MD, MBA: So downstream, the managed care company may not benefit from the investment of having given the more expensive drug.

Dennis P. Scanlon, PhD: We could think about that with pre-Medicare and Medicare, as well, right? If we get a handle on the population and do a bit of prevention, that can impact the Medicare program down the road.

Robert Gabbay, MD, PhD, FACP: I think there’s another opportunity, that as thought leaders, I think the endocrinology community could be more engaged with managed care in terms of driving formulary decisions and giving our input. I know that, typically, there will be an endocrinologist on a formulary committee, but they’re often not the most knowledgeable—the thought leaders in the endocrinology community. So, a little bit is on us to be able to be more involved and be able to help educate. Everyone is trying to do the best they can with the information they have, and we often have information that may not be available to everybody else and may be able to frame it in a different way.

John A. Johnson, MD, MBA: You’re exactly right. Like at, WellCare, and at most managed care companies, we have a pharmacy and therapeutics committee. We look at medications, back to your point of how soon these medications are available on the formulary. All of this is based on the evidence.

What we’re finding out is that in diabetes management, it’s an evolving dynamic environment. In the last 25 years, we’ve expanded the category of oral anti-diabetic agents by more than 10 individual categories. Therefore, the managed care community has to keep up with that information. It’s an evolving process.

Zachary T. Bloomgarden, MD, MACE: The fascinating thing is that over the past 6 months, we’ve learned of 3 different types of diabetes medicines that actually are associated with reduction in cardiovascular outcomes. That’s going to have to be integrated into how we treat people with cardiovascular disease, and also all people with diabetes whose risk of cardiovascular outcomes is, if not quite at the level of a person who’s already had a heart attack or a stroke, approaching that level.