2019 ADA Standards of Diabetes Care Unpacked for PCPs

Jay H. Shubrook, DO: I'm Jay Shubrook, family physician and diabetologist at Touro University California in Vallejo. Joining me today is Neal Skolnik, professor of family and community medicine at the Sydney Kimmel Medical College at Thomas Jefferson University in Philadelphia, Pennsylvania. He's going to talk about the brand-new American Diabetes Association (ADA) guidelines^[1] and the very specific changes to the prioritization of medications for the treatment of type 2 diabetes. Welcome, Dr Skolnik.

Neil S. Skolnik, MD: Thank you so much, Jay.

Shubrook: We have new 2019 guidelines and abridged standards of care for primary care providers. Tell us more about this.

Skolnik: This is big information—a joint statement^[2] of the European Association for the Study of Diabetes and the ADA on how we should approach medical management of type 2 diabetes. There are very few conditions that are more common or more confusing in primary care than the treatment of diabetes.

The statement comprises two important themes. The first is individualization of care and how to pick medicines. The second is what to use as the first injectable. There are major changes in each of these areas.

The first aspect of individualization of care is choosing the A1c goal. It should be around 7% or less for most patients. But remember: For younger patients with few comorbidities, it can be a lot lower than 7%, and for older patients who have multiple comorbidities, we can be more lenient than that usual 7% goal. An A1c above 8% may even be appropriate for many of our geriatric patients.

Let's move on now to choosing medicines. The first-line medicine, metformin, hasn’t changed. Why? Because it's inexpensive, well tolerated, doesn't cause weight gain, has a low incidence of hypoglycemia, and data show that it has good glucose-lowering efficacy. There are even some data showing that it helps with the endpoints we want it to help with: decreasing micro- and macrovascular disease. Let's not forget lifestyle modification—diet and exercise—as a foundational piece of any approach to diabetes. That said, we're not going to talk further about those two things.

What we all struggle with is what to choose as our second medicine, and this is where the new guidelines provide some very clear advice. We start by asking: Does the patient have established cardiovascular (CV) disease, congestive heart failure (CHF), or renal disease? If they do (and that encompasses about 20% of our patients), then we start with either a sodium-glucose cotransporter 2 (SGLT2) inhibitor or a glucagon-like peptide-1 receptor agonist (GLP-1RA) with proven CV benefit. The GLP-1s are preferred if someone's main issue is atherosclerotic heart disease. Evidence of benefit is strongest for liraglutide, favorable for semaglutide, and less certain for exenatide. With the release of the topline results from the REWIND trial, which were issued after the guidelines were published, we now know that dulaglutide has CV benefit in a broad population and is also on the map.

Among SGLT2s, we have excellent outcome data on empagliflozin and canagliflozin, both of which are mentioned in the guidelines. But things are happening quickly. After the guidelines came out, the DECLARE trial^[3] results, looking at dapagliflozin, were published. That trial did not show a lower rate of MACE (major adverse cardiovascular events) with dapagliflozin, but treatment with the drug did result in a lower rate of CV death or hospitalization for heart failure. So the SGLT2s are also on the map.

A key take-home point: If your patient has CV disease, think GLP-1RA or SGLT-2 inhibitor.

If someone has CHF, an SGLT2 is preferred. If someone has established atherosclerotic CVD, a GLP-1 is preferred. If you can't use one, then use the other. And if someone has established renal insufficiency, then an SGLT2 is preferred. The data are quite robust in regard to slowing progression of renal disease. This is something people are not that aware of and I do want to emphasize it. Just as we've become used to using an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin-receptor blocker (ARB) to slow progression of renal disease, the SGLT2s now have really solid data that they do that as well.

A second key take-home point: If your patient has heart failure, consider an SGLT-2 inhibitor.

Shubrook: That is a lot of information. I want to make sure I can summarize this in a way that is useful for our audience. First, we're going to start treating our patients with metformin and lifestyle changes. We're going to individualize our goals. That's not new, but it is important. Second, if someone has CVD, we're going to look at the GLP-1RAs or SGLT2s that have evidence that they reduce CVD. If someone has renal disease—and this is a very important new addition—the SGLT2s have good evidence that they help protect against the progression of renal disease. We also know that the SGLT2s have robust data in support of their use in treating heart failure, above and beyond their effect in diabetes. Is that correct?

Skolnik: That is absolutely correct. And for renal disease, if you can't use an SGLT2, then the GLP-1s have data as well.

A third key take-home point: If your patient has chronic kidney disease, think SGLT-2 inhibitor early and GLP-1RA later.

Shubrook: You said that this affects 20% of our population. But let's say I have a 45-year-old patient. He is newly diagnosed, has done lifestyle modification, and is taking metformin. His A1c is not at goal, but he doesn't have any of those conditions that you mentioned. What do the guidelines say about that?

Skolnik: Then we go on to the rest of our algorithm. Let me take each of these issues in order. If the main issue is that we want to minimize hypoglycemia, I think it's easier to think of what not to use than what to use. Don't use a sulfonylurea and don't use insulin. We can use a dipeptidyl peptidase 4 (DPP-4) inhibitor, a GLP-1RA, an SGLT2 inhibitor, or thiazolidinediones (sometimes called TZDs or glitazones).

A fourth key take-home point: If your patient is worried about hypoglycemia, avoid sulfonylureas and insulin.

Okay, the next major issue—and this is a big deal—involves whether we want to minimize weight gain or promote weight loss. We all know how our patients with type 2 diabetes struggle over many years with weight issues. And we often give them medicines like sulfonylureas or insulin that make them gain weight. If weight is an issue, which it is for so many of our patients, the preference is toward using a GLP-1 receptor agonist or an SGLT2 inhibitor. Why? Because these classes of medicines help patients lose weight—up to 10 pounds with some of the medicines in these two classes. That compares with, for example, starting insulin where a patient can gain 5-10 pounds. So the difference is important.

A fifth key take-home point: If the patient's main goal is to lose weight, think GLP-1RA or SGLT-2 inhibitor.

Many of our patients don't have great insurance or have no insurance. What do we do when cost is an issue? For those people, sulfonylureas are great choices. You can get a sulfonylurea for $4 on the $4 drug lists [available through several national pharmacies]. TZDs are also good choices.

A final key take-home point: If cost is the major issue, think sulfonylurea, metformin, or a TZD.

In summary, we have lots of choices now. Instead of them being a source of confusion—and when you're confused you just default to what you've always done—let's move forward with a well-thought-out, well-developed algorithm where we first ask: Does the patient have underlying CVD, stroke history, or peripheral vascular disease? If so, let's use a GLP-1 or an SGLT2. Is the patient at high risk for CHF? Then use an SGLT2; if not, use a GLP-1. Does the patient have renal insufficiency? If that's the case, then an SGLT2 is preferred. Or if we can't use that because the renal insufficiency is too severe, then choose a GLP-1.

Moving forward from there, looking at weight—which I believe is the next most common issue—if we can, use an SGLT2 or GLP-1. If we're concerned about hypoglycemia, again, stay away from sulfonylureas and insulin. When cost is an issue, a sulfonylurea or a TZD is a great choice.

Shubrook: I really appreciate you summarizing those things; that is quite helpful. For those providers who want to know more, take a look at the new ADA guidelines.^[1,2]

Neil serves on the Primary Care Advisory Committee of the ADA. That committee is responsible for the abridged standards of care that were written specifically by primary care for primary care. The standards have all of this guidance, both in written and table format. It is a great reference.

Take-home point: If you want to learn more, see the 2019 ADA Abridged Standards of Care, written for primary care from primary care.

Thank you for your time today. I appreciate your discussion of this exciting and important topic.

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