GLP-1 Agonists and Weight Loss in T2D

John B. Buse, MD, PhD: I think we were the first group to ever use GLP-1 [glucagon-like peptide-1] receptor agonists in the clinical trial in patients with type 2 diabetes, and that was in 1999. If I remember correctly, the first drugs were marketed in 2005. I might be wrong about that, but it’s been awhile since exenatide was first released. Literally being blown away by how these drugs worked in clinical trials, I think our group has used a lot of GLP-1 receptor agonists. And I don’t really know what the impact of that pattern or practice has been on our patients, but I can tell you that early in my career it was rare to have a patient with diabetes in their 70s or 80s who was doing well.

We have lots of patients in their 80s and 90s doing well today. Certainly, part of the credit goes to better cardiovascular risk management. Certainly, some of the credit goes to better technologies in general around cardiovascular risk reduction. But I do think that these GLP-1 receptor agonists, and now the SGLT2 [sodium-glucose cotransporter-2] inhibitors have meaningful cardiovascular benefits, and people are living longer. More of my patients are losing weight than gaining weight, I think, because we’re relying on these drugs more and more. And I have to believe that’s part of the benefit of this approach—weight loss instead of weight gain and lesser risk of hypoglycemia or no hypoglycemia. So it’s been a great 20 years with the GLP-1 receptor agonist class, for me, in my practice.

John Anderson, MD: Almost all our patients with type 2 diabetes, with very rare exceptions, especially here in the Southeast, are overweight or obese. Almost every one of my patients with type 2 diabetes could benefit from weight loss.

Most of the agents we had in the past that we gave patients with type 2 diabetes caused weight gain. And almost all our patients could use weight loss. So TZDs (or thiazolidinediones) like pioglitazone, and insulin, and sulfonylureas, all tend to cause weight gain. It is wonderful to have a couple of classes of agents that have that nonglycemic benefit of weight reduction. And in my experience, almost all my patients on a GLP-1 receptor agonist will lose some weight.

I think the problem is you just don’t want to overpromise it to the patients. If you tell a patient, “You’re going to lose 20 pounds,” and they lose 8, they’re disappointed. If you tell them, “You have the chance to lose some weight,” then “some weight” is a benefit. Now, we’ve all seen patients who don’t lose any weight. We’ve seen patients who lose 8 to 10 pounds, and we have those oh-wow moments where they’ve lost 20 to 25 pounds. It’s hard to predict who’s going to be in that really robust weight-loss category.

So my message would be: Don’t overpromise the weight loss, but it’s wonderful when patients come in and they’re proud of themselves. Not only is their A1C [glycated hemoglobin] down, but they’re losing weight. And I’ll tell you this, in a lot of cases I think some of these patients have struggled so much with weight loss, and have failed so many times, that when they start to see that they’re actually losing weight for the first time, it really kicks in and motivates them. “What if I do what Dr. Anderson says and I actually go to the gym or I start a walking program? What if I actually try to eliminate some of the carbohydrates from my diet?“ So I have seen patients for whom this has kick-started better behaviors.

Vanita Aroda, MD: So when we choose our agent, we primarily look at their glycemic level—where they are currently and where we want them to go. The weight loss is that added benefit, and patients really, really appreciate this. The exact opposite happens when they are started on an agent that can promote weight gain. We see this, for example, when we start insulin therapy. Patients get frustrated when their weight goes up. Even if their glucose is going down, they get frustrated with weight gain because weight, itself, is its own independent risk factor for multiple comorbidities. So what we’ve seen in care is when patients start losing weight, or when we see that the agent we use helps make them feel empowered so that they can start to lose weight, it goes hand in hand with their overall care.

Transcript edited for clarity.