Treating Type 2 Diabetes with ASCVD

A 60-year-old male with documented ASCVD, obesity with BMI of 34, and type 2 diabetes presents for care. The patient reports he's currently feeling well without episodes of hypoglycemia. Current laboratory assessment includes the following. A1C is 8.6 % and his estimated GFR is at 62. Current medications include metformin at optimized dose and a sulfonyl urea.

Which of the following represents the nurse practitioner's next best action?

A. continue on current therapy and arrange for a three month follow up

B. discontinue the metformin and add a DPP4 inhibitor

C. add a GLP-1 inhibitor and discontinue the sulfonyl urea

D. add basal insulin and titrate to fasting glycemic goals

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Transcript

Voiceover: Welcome to NP Certification Q&A presented by Fitzgerald Health Education Associates. This podcast is for NP students studying to pass their NP certification exam. Getting to the correct test answers means breaking down the exam questions themselves. Leading NP expert Dr. Margaret Fitzgerald shares her knowledge and experience to help you dissect the anatomy of a test question so you can better understand how to arrive at the correct test answer. 

So, if you're ready, let's jump right in.

Margaret Fitzgerald: Treating type 2 diabetes with ASCVD. A 60-year-old male with documented ASCVD, obesity with BMI of 34, and type 2 diabetes presents for care. The patient reports he's currently feeling well without episodes of hypoglycemia. Current laboratory assessment includes the following. A1C is 8.6% and his estimated GFR is at 62. Current medications include metformin at optimized dose and a sulfonylurea. Which of the following represents the nurse practitioner's next best action? 

A. Continue on current therapy and arrange for three-month follow-up. 
B. Discontinue the metformin and add a DPP4 inhibitor. 
C. Add a GLP-1 inhibitor and discontinue the sulfonylurea. 
D. Add basal insulin and titrate to fasting glycemic goals.

The correct answer is C. Add a GLP-1 inhibitor and discontinue the sulfonylurea.
Where should we start with this question? First, let's determine what kind of a question it is. Given that we're provided with a number of diagnoses for this patient and the fact that the patient is not at treatment goal, his A1C is obviously too high. Uh, clearly this is a plan/intervention question. Now, it could also be viewed as an evaluation question because the patient is currently under care and the end product of the question is an adjustment of current therapies. Although, at the same time, we're given an option here where we're not going to do anything about his therapies. 

As I've mentioned in many other podcasts, most medication questions are at their core safety questions. And what's one of the biggest issues with this patient? He not only has type 2 diabetes, but he also has established atherosclerotic cardiovascular disease, or ASCVD.

A key point in providing ongoing care for the person with type 2 diabetes with existing ASCVD is to avoid hypoglycemia. Hypoglycemia is inherently, of course, dangerous to anybody with diabetes. But for people with ASCVD, a hypoglycemic episode could trigger a cerebrovascular or cardiovascular event. The other part, the patient is nowhere near advised glycemic control for a person, and for this person, would likely be less than seven percent. Therefore, we have two major goals in treating this person. One is to help lower A1C, but the other is, of course, avoiding hypoglycemia.

Well, hypoglycemia is certainly, as I just mentioned, dangerous to anyone. We don't want to see it in particular in people with ASCVD. We're also given this person's estimated GFR which places him at stage 2 CKD. And, because I can't talk about cardiovascular disease, CKD, and diabetes without saying this is that remember: heart health is kidney health is brain health. All of these body parts are dependent on healthy blood vessels. So what we also want to keep in mind is people with established CKD who are on sulfonylureas are at higher risk for hypoglycemia.

As I help to prepare people for NP certification, I must say, few drug groups generate more questions than those for the treatment of type 2 diabetes. There are a number of major drug classes that are indicated for this treatment. And what I'm going to do here is walk you through the medication choice while giving you the rationale for each answer. Few other points before we hit the question. Please note that each question has two pieces of information or actions in it. Both need to be correct for the answer to be correct. Another comment, you’ll likely desperately want more information about this patient. I do, but please keep in mind the NP boards provide you with enough information to answer the question, but seldom anything extra.

So, one more time, let's walk our way through the question. A 60-year-old man with documented ASCVD, obesity with a BMI of 34, and type 2 diabetes presents for care. The patient reports currently feeling well without episodes of hypoglycemia. Current laboratory assessment includes the following: A1C equal to 8.6%, GFR equals 62. Current medications include metformin at an optimized dose and a sulfonylurea. Which of the following represents the NP’s next best action?
A. Continue the current therapy and arrange for three-month follow-up. That obviously is not correct and it represents something that's often called therapeutic inertia. That term is often used to describe the patient and the provider’s inertia, if you will, at changing a therapeutic plan when a patient is clearly not at therapeutic goal. I'm happy to hear he feels well. It’s great he’s not had any hypoglycemic episodes, but he’s taking a sulfonylurea, a medication what I call provides “dumb insulin release.” In other words, it’s the same amount of insulin release regardless of whether the blood sugar is 80 or 280. That’s what it does. It enhances insulin release from the pancreatic beta cells regardless of what blood sugar is. And therefore one of the major risk factors for the use of a sulfonylurea is the development of hypoglycemia. This hypoglycemia can be easily triggered by inadvertently skipping a meal, eating less food than was anticipated, there are a myriad of reasons. And to boot, as I briefly mentioned, the risk of hypoglycemia with sulfonylurea use is even higher in people with CKD because the med hangs around for so long. And one last point, remember, hypoglycemia triggered by a sulfonylurea can hang around for hours because the drug has such a long half-life. Bottom line, avoid sulfonylurea use in a person with ASCVD.

B. Discontinue the metformin and add a DPP4 inhibitor. This is also not correct. Now, one of the things I want to keep in mind—I don’t think metformin gets the praise it deserves. This is a medication that’s been around for somewhere in the vicinity of 40 years. It does have demonstrated cardiovascular benefit. However, we don’t have brand, shiny new cardiovascular benefit research on metformin. And this is in part because it has been generic for at least 20 years now, probably even more than that, which is one reason it’s so inexpensive. So whereas you’ll hear with things like the SGLT2, the GLP-1 agonist, you’ll see ongoing, very impressive data from research on their cardiovascular benefit, their benefit in CKD, etc., etc. We don’t have those data that are brand new on metformin, but trust me, the cardiovascular benefit is there. The ADA advocates that metformin use continue throughout type 2 diabetes therapy unless there is a contraindication. What’s the major contraindication for metformin use? It is advanced CKD, stage 4 CKD if you will, when the GFR is less than 30. His GFR is nowhere near less than 30. So why is it we discontinue metformin once the GFR is less than 30? At that point, lactic acidosis risk with metformin use goes way up. However, given that metformin works via being an insulin sensitizer, there is no hypoglycemia risk with that medication.

Now, what about the other answer here, though? A DPP4 inhibitor provides smart insulin release and is certainly a possibility instead of the sulfonylurea, but it would be with the metformin, not instead of the metformin. But here is one other part: DPP4 inhibitor use—this is a class of drugs with the “glyptin” suffix, sitagliptin, etc.—these do not provide added cardiovascular or renal benefit, two things we want to consider with this person.

And C, the correct answer here: Add a GLP-1 inhibitor and discontinue the sulfonylurea. This is clearly the best answer. Discontinuing the sulfonylurea eliminates his hypoglycemic risk; that alone is clinically helpful. In addition, GLP-1 inhibitor, particularly choosing one with demonstrated ASCVD benefit, can address two issues. One is of course his ASCVD, with demonstrated improvement outcomes with people with these common comorbid conditions and type 2 diabetes. In addition, I’m going to get much better glycemic control by enhancing what I call smart insulin release. In other words, insulin release in response to a rise in blood sugar. But if, like, let’s say the blood sugar was 80, the GLP-1 agonist would not be saying to the pancreas, “Hey, hey, hey, we need more insulin here.” But now the person eats a significant carb load, blood sugar goes up to 180, and the GLP-1 agonist will be saying to the pancreas, “Come on now, we need some insulin to cover that spike in blood sugar.” We also know that GLP-1 agonists also have noted benefit in CKD. One other part here, this person has a diagnosis of obesity, and the GLP-1 agonists provide a benefit to that by encouraging weight loss through a variety of mechanisms, but one of these is increased satiety by slowing GI emptying, and that typically leads to weight loss.

Just to wrap up here, not all GLP-1 agonists have the FDA approved indication for ASCVD or renal benefit, but for the purposes of the boards, they’re more likely to talk about the GLP-1s as a drug class rather than to throw you a curveball question like, “One option is, you could prescribe semaglutide, which does have all these benefits FDA-labeled, and then an older GLP-1 agonist like exenatide that doesn’t have them recorded.” They’re not going to do that. They’re not going to do that on the boards; it probably will be simply more GLP-1 agonist.

And option D, obviously incorrect since we just went over the correct option: add basal insulin and titrate to fasting glycemic goals. This also is incorrect. Yes, his A1C’s out of goal, but let’s look for a medication that can do more than one thing, and here it would be the GLP-1 agonist. In addition, of course, basal insulin carries with it a much, much lower hypoglycemic risk than rapid-acting insulin, but insulin is the drug class in the treatment of type 2 diabetes with the greatest hypoglycemic risk.

Just to wrap up here, you might all be listening to this and saying, “Yeah, but what about an SGLT2i?” Could have been a great choice on this one, but it was not in any of the answers, was it? So, therefore, I’ll make sure I talk about that in a future podcast, but we always need to deal with what we’re given in questions rather than saying, “Yeah, but, yeah, but, I want to prescribe something else.” Go with what’s in front of you.

Key takeaways in the treatment of type 2 diabetes. Avoiding problematic medication and choosing those with the most benefit for that particular patient should guide your treatment plans.

Voiceover: Thank you for listening to NP Certification Q&A presented by Fitzgerald Health Education Associates. Please rate, review, and subscribe to this podcast. And for more NP resources, visit fhea.com.