GLP-1 Agonist Therapy in a Patient With T2D and CVD

APRIL 15, 2019
MD Magazine Staff

John Anderson, MD: When you’re thinking about this patient it’s like, “OK, what can I put this patient on? Could I put this patient on a DPP-4 [dipeptidyl-peptidase-4] inhibitor?” DPP-4 inhibitors are nice. We know that in all of the clinical trials they’re noninferior. In other words, they’re safe, but they provide no extra cardiovascular risk reduction.

We know that there are 2 SGLT2 [sodium-glucose cotransporter 2] inhibitors that provide extra cardiac risk reduction. They also don’t tend to have hemoglobin A1C [glycated hemoglobin]-lowering effects that are as potent as a GLP-1 [glucagon-like peptide-1] receptor agonist, which is why the AACE [American Association of Clinical Endocrinologists] guidelines still say that after metformin, GLP-1 receptor agonists, in general, are the preferred agent over SGLT2 inhibitors. So when I look at this patient, she’s got an A1C of 8.2%. If I give her an SGLT2 inhibitor, I can lower her 1%, or maybe just slightly more than 1%, but I’m not going to get that robust lowering that I’m going to get with a GLP-1 receptor agonist.

If this patient had heart failure, or if this patient had a kidney that was compromised, then the SGLT2 inhibitor might be the preferred agent. But in this patient, for whom atherosclerosis seems to be the issue, the GLP-1 receptor agonist, in my opinion, is the preferable class of drug.

John B. Buse, MD, PhD: The next step in treatment, if I were seeing her in clinic, would be a discussion first around lifestyle issues. Are there things that she can do to promote weight loss, which is a very important goal in the setting of diabetes? And then, I’d primarily point out to her that recent clinical trial data suggests that 2 classes of diabetes drugs are associated with cardiovascular benefits, preventing heart attacks, strokes, and cardiovascular death. And in her setting, with early cardiovascular disease [CVD] and inadequate blood sugar control, using one of these agents is really important for her. The trials are associated with clinically meaningful benefits in the order of 15% to 20% reductions in the endpoints that I discussed, which really puts it on par with the benefits of statin therapy, ACE [angiotensin-converting enzyme] inhibitors, and it’s arguably greater than aspirin therapy in the setting. So it’s really important that we get patients on these medications when we can.

In this case, the 2 choices for reducing cardiovascular risk would be an SGLT2 inhibitor or a GLP-1 receptor agonist. The SGLT2 inhibitor is a pill. The GLP-1 receptor agonist is an injectable. Her blood sugar control isn’t so bad that we’d need the additional power of an injectable agent, per se, but I do think that the evidence of benefit for reductions of heart attack, stroke, and cardiovascular death—the so-called MACE [major adverse cardiac events] endpoints—is greater with a GLP-1 receptor agonist than a SGLT2 inhibitor.

The new guidelines say either/or, but I tend toward using GLP-1 receptor agonists where the dominant problem is cardiovascular disease, and I am more likely to use the SGLT2 inhibitor when the dominant problem is heart failure or chronic kidney disease.

John Anderson, MD: I am asked all the time: What about your patients? How do you get them to take an injection? I think it starts with the provider. I think the needle phobia is a lot of times initiated by the provider, and that includes the nurse practitioner, PA [physician assistant], and physician. You know, they all say, “My patients won’t do an injection.” Yes they will, just talk to them about it.

A lot of times these patients have needle phobia because of the thought of what the size of the needle is. They think it’s going to be a 20-gauge needle in their antecubital fossa like what you’re drawing blood with. I’ve had plenty of experiences of taking a patient, showing them a 32-gauge ultrafine needle, and having them do an injection. They don’t even feel it. In fact, it’s way less painful than sticking your fingers. We also have agents now that are once a week, for which you may even have a hidden needle. So there’s a lot of ways to talk about this with your patient, especially when you say, “Here’s the reason I want you to take this,” and let them participate in the decision making. The other part of this is sometimes when they hear injection, they think insulin. So that’s a different bias, and a different prejudice, and a different concern that you have to address with the patient. But I have had very few problems getting my patients to consider an injection if you sit down and talk with them about the reasons and why you’re recommending it to them.

John B. Buse, MD, PhD: It’s always a bit of a touchy subject with providers, with primary care doctors, and with other providers and nurse practitioners, as well as PAs, pharmacists, certified diabetes educators, as well as patients when we decide to go to injectable therapy. The truth of the matter is nobody really wants to take a shot. These new GLP-1 receptor agonists all come in pen devices. They’re very easy to use. One of them, in particular, dulaglutide, you never even see the needle. It’s completely hidden. I sort of sell it to patients with the idea that it’s like a magic wand: You just put it on your body, and the magic happens.

These drugs are associated with weight loss, very powerful glucose lowering, but no increased risk of hypoglycemia, absent the risk that comes from taking other medications at the same time like sulfonylureas or insulin. I’m quite successful with getting patients to take those medicines—the GLP-1 receptor agonists—and in general, I think the vast majority of patients recognize the tremendous effect in lowering glucose and this hope and promise of reducing cardiovascular risk.

Transcript edited for clarity.

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