Choosing Among Antidiabetes Agents

Peter L. Salgo, MD: I want to point out what’s going on here. We’ve got an endocrinologist, cardiologist, and somebody who’s seeing patients in a primary care setting.

Stephen A. Brunton, MD, FAAFP: Help, help.

Peter L. Salgo, MD: That’s my question. What is the role of the cardiologist and the endocrinologist? You’ve been asking them for help, now, for a question-and-a-half.

Stephen A. Brunton, MD, FAAFP: I’m sorry I did that.

Peter L. Salgo, MD: And you know what I heard? What is the role out there, in your view, for these experts?

Stephen A. Brunton, MD, FAAFP: To be able to manage patients, I think other specialty experts are very helpful. The truth of the matter is that 85% (at least) of diabetes is managed in a primary care setting. And typically, these patients aren’t referred. We do manage the whole person. We have to make these decisions based upon the best data. Being purposely vague doesn’t help me. I need something that’s very, very specific. So, I think that your point, Peter, is a very important one.

Christian T. Ruff, MD, MPH: Yes. The truth is, you’re going to get the biggest bang for your buck out of the high-potency statins. So, that certainly is where you start. The issue, then, becomes a healthcare society as well. I do believe that drugs, such as acetamide, have a modest reduction, but there’s very little downside to it. And so, I tend to be very aggressive. And even though that was a trial that studied patients post-ACS [acute coronary syndrome], in patients who still have residual LDLs [low-density lipoproteins] that are elevated (certainly around 100 mg/dL or above or even above 70 mg/dL), I think that’s a low-cost option (to add acetamide) because you will get another modest reduction. Where it becomes more problematic is now that we have new very expensive drugs, like PCSK9 [proprotein convertase subtilisin/kexin type 9] inhibitors, do I believe medically that if we added that on top of patients that we would get further reductions? Yes, but could we really ask the healthcare society to pay for that kind of price? I think, for those kind of patients, you need to have very extreme values for where we’re targeting. They’re at astronomical risk and we have to lower it. It can’t be population-based.

Peter L. Salgo, MD: There’s a whole bunch of drugs that are not directly lipid-related, that are diabetes-related, if you will, if we can put them in that silo. There are a lot of available classes of medications out there. How do you go about beginning therapy? How do you choose among all of these classes of medicines? What are these classes, anyway?

Stephen A. Brunton, MD, FAAFP: There are a number of classes. The problem is that, often, our choice is being limited by formulary restrictions.

Peter L. Salgo, MD: Let’s put the formulary to the side.

Stephen A. Brunton, MD, FAAFP: I wish we could, but in truth, I think pretty much everybody who can tolerate them would start with metformin for type 2 diabetes.

Peter L. Salgo, MD: That’s old-fashioned stuff.

Stephen A. Brunton, MD, FAAFP: It’s old-fashioned stuff that works very well. It’s inexpensive, and about 80% of the patients can tolerate it. When you don’t, then you have another problem. Then, we go into a step-wise approach. And, frankly, all the guidelines suggest that each of the agents has benefits. You have to evaluate these agents in terms of cost and side effects. I always say that safety trumps efficacy, every time. So, you really look at what the patient can tolerate.

The newer classes of agents, the GLP-1 [glucagon-like peptide-1] antagonists and the SGLT2 [sodium-glucose co-transporter 2] inhibitors, offer some real opportunities. We now understand that, physiologically, it’s not just insulin deficiency and insulin resistance. There’s a number of different organs, and people are talking about 11 or 14 physiological deficiencies. So, addressing a number of those deficiencies gives us the opportunity…

Peter L. Salgo, MD: We have all these epiphenomena with all these new drugs. They have effects on weight. There’s certainly a hypoglycemic effect, and when we talk about hypoglycemia, what I mean is, physiologically significant low blood sugar that’s pathologic. And then we also have prior cardiovascular disease and kidney disease as risks. How important are all these and how do you weigh them?

Rosemarie Lajara, MD, FACE: It’s extremely important. And, actually, they’re incorporated into the ADA [American Diabetes Association] decision-making algorithm. You have different criteria in a conversation with the patients: the anticipated efficacy, the anticipated effect in weight (whether it’s weight neutral or weight gain), hypoglycemia, adverse event profiles, and cost also are part of this discussion. Back maybe 20 years ago, when our options were quite limited, perhaps this narrative would have never even been considered. But, nowadays, these profiles for the new age, it’s the modern era of diabetes. These agents allow us to have this beautiful exchange.

Peter L. Salgo, MD: It’s an embarrassment of riches, is what you’re telling me?

Rosemarie Lajara, MD, FACE: That’s right. Absolutely.

Peter L. Salgo, MD: But, still, every one of these things needs to be considered. If you put somebody on a drug and their weight goes up, they’re going to say, “But I wanted to lose weight.”

Stephen A. Brunton, MD, FAAFP: And that’s really one of the challenges. You’ve got weight gain and you have hypoglycemia. The problem is that the cheapest agents (potentially, sulfonylureas), are effective, but they do have weight gain and they have hyperglycemia associated with their use. So, you have a GLP-1 agonist that works very well, that doesn’t do those kinds of things, but they’re priced out of the range for many of the patients. Plus, it’s an injectable and you have issues that you have to discuss with the patient, as well.

Peter L. Salgo, MD: Right.

Karol E. Watson, MD, PhD, FACC: And how many patients do you have where you say, “I have this great new drug that will lower your A1C, but you may gain 5 pounds.”

Transcript edited for clarity.