Video: GLP-1 Medications Revolutionize Obesity and Diabetes Care, With Exciting Advances on Horizon

In an interview with Pharmacy Times®, Donna Ryan, MD, professor emerita from the Pennington Biomedical Research Center in Baton Rouge, Louisiana, discusses the current landscape of glucagon-like peptide-1 (GLP-1) receptor agonists, emphasizing their dual role in diabetes and obesity treatment. Ryan provides an overview of currently approved GLP-1s on the market, including semaglutide (Ozempic, Wegovy; Novo Nordisk) and tirzepatide (Mounjaro; Eli Lilly), and their numerous benefits beyond weight management, such as in controlling cardiovascular risk and mitigating chronic kidney disease.

Closed captions for this video were auto-generated by artificial intelligence.

Pharmacy Times: Could you provide a brief overview of the current landscape of GLP-1 medications?

Donna Ryan, MD: You know, everybody thinks the GLP-1 medications are brand new and ultra exciting. Well, they are ultra exciting. But let me tell you: we've had GLP-1 medications around for 20 years. In fact, the first one was approved for diabetes in 2005; that was exenatide (Byetta; Amylin Pharmaceuticals, Eli Lilly). The first one was approved for obesity in 2014; that was liraglutide (Victoza, Saxenda; Novo Nordisk). So, these are medications we've known for a long time. But native GLP-1, the hormone in our bodies, has effects on appetite, and it also has effects on controlling blood glucose. When your blood glucose level is high, it promotes the secretion of insulin and lowers it. The drugs have really been developed in 2 main areas: for diabetes and for obesity. But look: nobody got interested in this until about 2022, when semaglutide (Ozempic, Wegovy; Novo Nordisk) came out. Semaglutide had been around a few years for diabetes, as Ozempic, and it was approved as Wegovy for obesity. The data in people who don't have diabetes show that the weight loss was around 15% to 17%, much higher than we had gotten in prior obesity medications. This is an average weight loss of 15 to 17%. Then, tirzepatide (Zepbound, Mounjaro; Eli Lilly) came out. This is both a GLP-1 and gastric inhibitory polypeptide (GIP) receptor agonist. So, it's hitting the receptors for 2 of those gut hormones. What's important about that one is that it was associated with a weight loss average of 22.5%. This double-digit weight loss really got the public interested, but it's the doctors, I think, that really became interested in 2023 when the SELECT trial came out. It showed that this medication could prevent the second heart attack, stroke, or sudden death in people who had established cardiovascular disease. That's called a secondary prevention trial, and we had never seen anything like that before with our medications for obesity, so it really was quite a big deal. It's a combination of both the amount of weight loss that patients appreciate and the effect on disease modification, the prevention of cardiovascular disease, that really has everyone so excited.

Right now, the drugs that are available that produce a lot of weight loss for people with obesity are Wegovy—that's semaglutide—and Zepbound—that is tirzepatide. For diabetes, the same molecules are out there as Ozempic and Mounjaro. A little confusing, but believe me, just 2 molecules are good for both diabetes and weight management. So that's what we have available. There are still the other older GLP-1 medications. They don't produce as much weight loss, and they don't produce as much glycemic control, so people are less interested in them, but they're still good medications.

Pharmacy Times: Are there any new, expected study data or approved indications on the horizon or in development?

Ryan: First of all, let's go over some recent discoveries. You know, I think the disease-modifying discoveries are the ones that have really captured people's attention. So tirzepatide has a label indication now for obstructive sleep apnea—it really has a huge impact. It reduces the apnea-hypopnea events that occur in people who have obesity-related obstructive sleep apnea. So that's big news. But we're also seeing clinical trial data come out that these medications are showing efficacy in heart failure (HF), HF with preserved ejection fraction especially, and in prevention of progression of kidney disease. Then there are lots of clinical trials underway; we don't have data yet, but clinical trials are underway looking at if these drugs may have potential for neuroinflammation. So, things like Parkinson disease (PD) or Alzheimer disease (AD) or dementia; that would be very exciting. There's even an interest in these drugs as potential uses for smoking cessation and for addiction disorders. There are lots of things that we don't know about yet but that are garnering a lot of attention.

I guess everyone is also really excited about the future of this class. What we're doing is we are adding agents to that GLP-1 backbone. It's not really a structural backbone. It's just the idea that we have so many positive attributes with GLP-1; well, if we add this compound to it, we could get even greater efficacy. There are 2 big studies that are out there that everyone is very interested in, and that is the combination of semaglutide with a long-acting amylin; that is called CagriSema. We're expecting the phase 3 results to come out on that any day—very excited about that. And then the other, there's what's called a single molecule triple agonist. You know, tirzepatide was GLP-1 and GIP. Well, this molecule has three: GLP-1, GIP, and glucagon. It's called a triple agonist, and it's also in phase 3. We want to see those results because the phase 2 data make us expect that it's going to produce average weight loss in the high 20s. Those would be very powerful medications. We want to see what's going to happen there.