GLP-1 Receptor Agonists in Cardiometabolic Syndrome

Robert A. Gabbay, MD, PhD: GLP-1 (glucagon-like peptide-1) receptor agonists have also been shown to reduce cardiovascular mortality. That started with the LEADER trial—a trial that was designed to look at cardiovascular safety as mandated by the FDA for all new diabetes drugs. To everyone’s surprise, and honestly delight, there was a reduction in cardiovascular mortality associated with the use of GLP-1 agonists. That was with liraglutide. Then, a subsequent study was done with a newer analog, in the SUSTAIN Study, also corroborating the same results—a reduction in cardiovascular risk.

So, these are drugs that have a number of benefits. They improve glucose control, they lead to some weight loss, and now, they also reduce cardiovascular disease and mortality. And they do all this in a way that doesn’t lead to hypoglycemia. In a sense, if you’re looking for a drug for diabetes, this class really is ideal in many ways. The one challenge with it is it requires injection. But interestingly, in the LEADER trial where they looked at quality of life of patients that were either on liraglutide or placebo, those that were on liraglutide actually had no worse quality of life. They were injecting a medication on a daily basis, but it didn’t seem to impact their quality of life. One wonders whether that was because of the weight loss effect that people were happy about, and if it offset the inconvenience of doing injections.

Obesity is one of the biggest challenges in the management of type 2 diabetes, and it’s been very difficult to find strategies that are effective. Lifestyle efforts are important and recommended, and probably underutilized and underemphasized, and require a multidisciplinary approach. But in the absence of that being effective, we need to think about other therapies.

If we were looking for something that would be ideal for the treatment of diabetes, we’d look for something that would improve glucose control, that would not cause hypoglycemia, and, because obesity is so common, can reduce weight and certainly not lead to weight gain (as the sulfonylureas can do). Those 3 qualities are exactly what the GLP-1 agonists do. And then, one added bonus beyond all of that is not only do you have the better glucose control and the weight loss, but you also have a reduction in cardiovascular mortality that’s been shown, now, in 2 studies.

Transcript edited for clarity.