Raising the Bar on Cardiovascular Benefit

John Anderson, MD: I think payers, whoever’s in charge of the purse, need to be looking at these newer medications. They’re not just newer medications that we’re talking about because they’re newer medications. There’s more efficacy. There’s not a single older agent that can provide me with an efficacy of a GLP-1 receptor agonist. You’re looking at most patients out there with baseline A1Cs of 8.1% to 8.3%. They have 1.5% A1C reductions. Some of the SGLT2 inhibitors are up to 1% or 1.1% A1C reductions, and they’re not making our patients gain weight or causing hypoglycemia, which is safety for our patients. And when you don’t cause hypoglycemia, I don’t have to check my glucose as often, so I’m saving on strips. I’m saving on ER visits.

There’s a reason that we recommend these newer medications: It’s because they’re better, they’re safer, and they now have perhaps cardiovascular benefits for our patients. I know they’re expensive, and bringing new products to the market is expensive, but we need to find a way for patients to be able to access this—especially the most vulnerable of our patients, who are elderly Medicare patients for whom we see the most restrictions on medications and for whom cost drives a lot of the decision making, despite the fact that you may be pushing them to medications that are not nearly as safe and certainly don’t have the cardiovascular benefit.

It’s important to treat our patients with type 2 diabetes aggressively, early. A lot of studies show that if you can get them down and keep them down for a long period of time, even if they lose control later, they still have markedly reduced cardiovascular events and microvascular events. And now that we see cardiovascular outcomes trials, the thought is that that’s also true for these agents. The other thing I’d like to go back to is the ADOPT trial: Let’s look at sulfonylureas and the time to failure, 2 years. They are the least durable medication on the market. Forget the weight gain, forget the hypoglycemia—their durability is not good.

Metformin is a little bit better, TZDs [thiazolidinediones] in the ADOPT trial are perhaps the best. I can tell you I’ve got patients who I have on metformin and a GLP-1 receptor agonist, and I put them on it 10 years ago. They’re still on the same medicines. I haven’t touched their diabetes in 10 years. I’ve dealt with their back pain, their depression, menopausal hormone replacement, and everything else that we do in primary care, but I haven’t touched their diabetes. And so, some of these questions in addition to the cardiovascular outcomes are about the durability of the effect of the medication. For example, with GLP-1 receptor agonists, are we stabilizing beta cell mass? Are we preventing apoptosis and loss of beta cell function? Are we slowing that progression to ultimate beta cell failure and the need for insulin replacement? I think so. A lot of experts think so. We haven’t had as much time in the marketplace and in clinical experience with SGLT2 inhibitors, but if you look at some of the clinical trials, they don’t tend to regress back to baseline. My patients who have been on SGLT2 inhibitors for 3 years are doing great. So, a lot of this is, are we using better medications? Can we slow the progression of the disease? Can we preserve not only A1C but also their health longer with the newer medications? I firmly believe we can.

We don’t have a lot of new classes of medications coming in, but we do have a lot of new co-formulations. Now we have 2 basal insulins with GLP-1 receptor agonists that save patients injections. We have some new SGLT2 inhibitors entering the marketplace. There’s a lot of investigation, but I don’t see anything in the next 2 to 3 or 4 years on the horizon that is going to be, “Oh wow, here comes the new, latest, greatest class of medication.” I think what we have for type 2 diabetes are fantastic medications. One of our biggest problems with getting the results that you see in the clinical trials in our patients is adherence. They get hypoglycemic, and they stop the medication. They gain weight, and they stop the medication. They feel better because they’ve lost weight. They feel better because their A1C is down. They feel better because their diabetes is better controlled. Guess what? I’m going to tend to refill my medication more.

I think right now, for type 2 diabetes, we have a surplus of good medications. The key is to teach those who take care of diabetes—particularly the nonexperts, the primary care providers, nurse practitioners, physician assistants, and primary care physicians—how to best use these agents, and then make sure that we get access for these medications for our patients. I think it’s critically important as we look at the next 10 years in diabetes in the United States that we find a way to slow the progression of this disease, use better medications, and, as we’ve talked about, maybe even prevent heart attack and stroke down the line.
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