Choosing a First Injectable in Type 2 Diabetes: Try a GLP-1

Jay H. Shubrook, DO; Neil S. Skolnik, MD


February 11, 2019

This transcript has been edited for clarity.

Jay H. Shubrook, DO: Hi. I'm Jay Shubrook, a family physician and diabetologist at Touro University California in Vallejo. Today we're going to discuss the brand-new 2019 American Diabetes Association (ADA) Abridged Standards for Primary Care[1] and specifically talk about the hyperglycemic guidelines, which include some important changes for primary care. With me is Dr Neil Skolnik, a professor of family and community medicine at the Sidney Kimmel Medical College, Thomas Jefferson University, in Philadelphia, Pennsylvania. Neil, we're happy to have you with us today.

Neil Skolnik, MD: It is a pleasure to be here.

Shubrook: The guidelines came out in January 2019 with important changes, especially for primary care. Today we're going to talk about that first injectable medication for type 2 diabetes. When I think about a first injectable, I just assume that the person's diabetes is out of control and they go on insulin. Tell me more about how this has changed.

Skolnik: That's what a lot of people assume. But these new guidelines are making suggestions for large changes in the way we practice. These are immensely credible, major guidelines[1,2] that come jointly from the ADA and the European Association for the Study of Diabetes (EASD).

Traditionally we've thought of insulin as "the injectable." But about 10-15 years ago, the glucagon-like peptide 1 receptor agonists (GLP-1s) came onto the scene. Initially, a lot of people asked, "Why would I use an injectable if it's not insulin?" Well, we found a lot of reasons why we should use them, which I'll go over in a few minutes. Let me first say that the technology around these products has advanced. GLP-1s that used to be given as twice-a-day injectables and then daily injectables have now become available as once-weekly injectables, making the idea of injectable therapy a lot more tolerable for our patients.

Shubrook: Absolutely. I know that when I tell my patients that there are injections that can help them lose weight, I see a big change in the acceptance of injections. Now that we can administer them less frequently, they are even more attractive to our patients.

Now there is an opportunity to give patients a medicine that helps control their blood sugars...and also helps them lose weight.

Skolnik: That is one of the important reasons why GLP-1s, not insulin, are now recommended as the first injectable for our patients with type 2 diabetes who have not reached their A1c goals with two or three oral agents. This is not an unusual scenario.

When you think about it, in the old days—which right now in medicine is prior to 2 months ago—we used to always start with insulin. Patients were afraid of insulin because it could cause hypoglycemic episodes and it predictably caused a good bit of weight gain, about 5-10 pounds. Now we're able to offer a GLP-1 receptor agonist as the preferred agent for the first injectable. Why is that? It's because of the characteristics of this class of medication, and those characteristics specifically include weight loss instead of weight gain.

Our patients with type 2 diabetes have struggled with weight loss for years. Now there is an opportunity to give patients a medicine that helps control their blood sugars, even in those who have not reached goal despite adherence to two to three oral agents, and also helps them lose weight. They can lose 5-10 pounds with this class of medications. These agents also have a very low incidence of hypoglycemia. Again, this is quite important and fairly astonishing.

When the GLP-1 receptor agonists have been compared with insulin in head-to-head trials, they are as good or better than insulin at lowering the A1c and controlling glucose. For those three reasons—efficacy, decreased hypoglycemia, and weight loss instead of weight gain—the new guidelines clearly recommend GLP-1 receptor agonists as the preferred first injectable for patients who have not achieved adequate control on two or three oral agents.

Shubrook: I want to fine-tune it a bit. Does that apply to everyone, regardless of the person's A1c? Is that everyone, regardless of the medical history? Who are the best people for a GLP-1 receptor agonist?

Skolnik: That's a great point. We always want to be careful about blanket statements. Since our time is limited, let's say that this applies to most people. Patients with a very high A1c, over 11%, who are symptomatic and losing weight may benefit from insulin as the first injectable. They may have an insulin deficiency, which will not be addressed by a GLP-1 alone. The other strategy we can consider for patients with very high A1c levels—over 10%, or 2% above their target—who are symptomatic as well is the fixed-ratio combination therapies that combine a GLP-1 with a basal insulin. Those are excellent choices for that group of patients because they can start at a low dose of GLP-1 combined with a low amount of insulin, thus helping to minimize weight gain and hypoglycemia as well as the gastrointestinal side effects of the GLP-1s, while providing better efficacy than you might get with either one alone.

Shubrook: What I'm hearing you say is that when considering a first injectable for someone on two or three oral meds who is not at goal, following the guidelines should lead to consideration of a GLP-1 as one of our first choices, for two reasons.

First, we're potentially going to get weight loss rather than weight gain. Second, we are going to have a lower risk for hypoglycemia with an equivalent, or sometimes more effective, lowering of the A1c.

I know we used to say that GLP-1s are always better than mealtime insulin, but now I'm hearing that they may be as good or better than even basal insulin as our first choice.

Skolnik: You hit the nail on the head.

Choosing Between GLP-1s

Shubrook: Now we also have evidence that GLP-1s may actually reduce cardiovascular (CV) risk. We know that insulin doesn't necessarily raise CV risk but it certainly doesn't lower CV risk, so that's icing on the cake for people who have established CV disease.

If you're going to use a GLP-1, how do you decide among them?

Skolnik: Good question. To be perfectly honest, I usually choose the GLP-1 that is in the formulary of the patient's insurance. Clearly, there are some differences among the different agents. I prefer if possible to use a once-weekly GLP-1 simply because that is easiest for our patients. The once-weekly formulations also appear to have positive CV benefits.

We know that liraglutide[3] and semaglutide[4] have had positive CV trials. And new information will soon be published on dulaglutide as well. Semaglutide [and dulaglutide] are once-weekly GLP-1s, and the data are rock-solid. From a convenience point of view, if possible, I pick a once-weekly, but really the choice is driven by what insurance will approve for the individual patient.

Shubrook: I also want to highlight, as we mentioned earlier, that if you have someone with a very high A1c who appears to be glucose toxic, insulin may be your better first choice. As you mentioned, insulin and a GLP-1 combination may provide even more benefits by reducing glucose toxicity in addition to some of the benefits of the GLP-1.

Skolnik: That's an important point. Also, when you combine the two medicines, you get better A1c lowering than you do with either alone.

Shubrook: These are a few important highlights of the new ADA Standards of Medical Care for Diabetes, which comes out in January every year. The new 2019 guidelines include substantial changes in the hyperglycemia algorithm for type 2 diabetes. Dr Skolnik is on the primary care advisory committee that writes abridged standards of care[1] by primary care for primary care, which is an excellent reference if you would like to see more about this topic. Thank you very much, Dr Skolnik.

Follow Medscape on Facebook, Twitter, Instagram, and YouTube


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.