PracticeUpdate: Diabetes

EXPERT OPINION 16

Dr. Sloane : I was wondering if you could tell me between basal insulin and GLP-1 agonist which agent should be used first in terms of treatment, and do you have a strategy in terms of when to use certain agents? Dr. Leahy: That is the perfect question because, in fact, we discuss all the time what should be the first injectable. If you approach it from a sort of clinical point of view and clin- ical trial point of view, I think the reality is that head-to-head would say basal insulin versus GLP-1 receptor agonists are pretty equivalent at improving levels of hemoglo- bin A1c even with reasonably high levels of A1c, but then there’s big differences. GLP-1 drugs come with a low rate of hypoglyce- mia, they come with weight reduction, they come with GI side effects. And basal insu- lin come with really the opposite, which is no real GI side effects or risk of hypoglyce- mia potentially, and the risk of weight gain. So the real answer to the question is, when you know those facts to communicate those facts to a patient and then really understand from the patient what of those are important to them and what are not, and in many ways you can choose either. Now, if you take one step back and say what would the specialty world suggest would be the preferred sequence? I think there’s a lot of specialists who feel we would want to start with a GLP-1 receptor agonist. The whole profile of weight reduc- tion, low rate of hypoglycemia, and the new information supporting cardiovascular pro- tection and renal protection with some of these drugs that’s pretty nice compared to Sequencing Injectable Therapies in Type 2 Diabetes Interview with John (Jack) L. Leahy MD by Jason Sloane MD Dr. Leahy is Director of Endocrinology at University of Vermont Medical Center, and Professor at Larner College of Medicine at UVM in Burlington, Vermont.

any feelings about that, in terms of efficacy or safety? Dr. Leahy: Well, so those drugs exist. We cur- rently have two preparations available in the marketplace. One, a long-acting insulin dula- glutide alongwith a dailyGLP-1 liraglutide, and onewith a short-actingGLP-1 with lixisenatide in combination with glargine, Lantus, insu- lin. What I think about them is that clinical trials have shown the combination is stun- ning. When you really look at the outcome of clinical trials on the background of almost starting therapy the attained levels of hemo- globin A1c are often in the mid-6s with some weight reduction as opposed to the stand- ard kind of weight gain that one sees with insulin alone. A relatively low rate of GI side effects, which is kind of interesting because one of the ways we use these preparations is relatively slow titration, and I think the clin- ical trials are really persuasive. There’s one I really like for both of these drugs, people who are essentially injection-naive compar- ing getting insulin alone, getting GLP-1 alone, or the combination product. And always the combination product does much better with attained levels of hemoglobin A1c, with a low rate of hypoglycemia and weight reduction. So they’re really pretty amazing products.

a basal insulin therapy. And then if that’s not enough you could add insulin later. So that’s kind of the sequence most people are talking about. Dr. Sloane: Great. That’s very helpful. Thank you. For patients who are already on basal insulin, and perhaps even on a prandial coverage of insulin, would you consider adding a GLP-1 and why? Dr.Leahy: Sure. I mean, if someone is not ade- quately controlledwhen you’re already using insulin therapy, then you have to add some- thing. And it turns out that adding a GLP-1 receptor agonist both conceptually and practically is a great choice, because if you think about what those drugs do is in some respects different than what insulin does. Now, if they’re on prandial insulin, of course, you’re having an effect on mealtime insulin. But the GLP-1s, they have weight protection, they have potentially cardiovascular protec- tion, they’re insulin sensitizers, they come with a reduced rate of hypoglycemia, and really one of the exciting kinds of research that’s been going on is to take people who are just on basal insulin and compare the next step. Do I add prandial insulin, do I add aGLP-1 receptor agonist? And it turns out you can do as well with a GLP-1 receptor agonist even when you give once a week, so that’s a pretty common strategy we do in the spe- cialty diabetes world. Dr. Sloane: Last but not least, there’s talk of combination therapy, so giving a little bit of basal insulin in combination with a GLP-1 agonist in the same treatment. Do you have

Dr. Sloane is an Endocrinology Fellow at Massachusetts General

Hospital, Boston, Massachusetts.

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