Transcript
Announcer:
Welcome to GI Insights on ReachMD. Today, Dr. Fernando Bril will be discussing pharmacologic management of patients with obesity and liver disease. Dr. Bril is an Assistant Professor in the Division of Endocrinology, Diabetes, and Metabolism at the University of Alabama at Birmingham Heersink School of Medicine. Let’s hear from him now.
Dr. Bril:
Because head-to-head comparisons are lacking when it comes to what we prescribe first, how we do combination therapy is a little bit of an art, like a lot of medicine is. When I'm in front of the patient, I think of them holistically. And I know that liver disease doesn't happen in isolation. These patients have increased adiposity. Many times, they have dysglycemia. They may have pre-diabetes or type 2 diabetes. They may have heart disease. They may have kidney disease. And especially if they have this increased adiposity, I try to focus on medications with known benefit in trying to produce weight loss, because, at the end of the day, obesity is driving a lot of this liver disease, kidney disease, and heart disease.
So for me, when I approach the patient, I think of a GLP-1 or incretin-based therapy as kind of the first line. You want to introduce that weight loss medication early on to try to help holistically, not only the liver, but all the other complications that are associated with increased adiposity. But we have to remember, when we are thinking about the liver, one medication may not be enough. It’s the same way for type 2 diabetes, hypertension, or dyslipidemia—many times we need combination therapies. For MASH, it's the same, so that's our starting point.
But that's why we need to know where we are starting. We need to know what the degree of liver disease is before we start medication, and then we need to monitor these patients to see where we are going. After 12 or 18 months of therapy, how is the liver doing? This will help us decide whether they will need combination therapy. And once they are on an incretin-based therapy, then you may want to combine with resmetirom if they are still not doing well, especially if the liver is doing worse after 12 to 18 months of therapy. So that's always an option. Start thinking about combination therapies.
We need to think that once patients have increased adiposity, they have a combination of complications for maybe genetic and some epigenetic or other factors. Some patients may have more liver disease, and they may progress faster to liver fibrosis. Others may have more significant kidney disease and progress faster to CKD. Others may have a heart attack and die even before they have kidney or liver disease. But all these are complications of that increased adipose tissue that becomes insulin resistant. So now they have increased insulin levels with a lot of lipotoxicity, because that adipose tissue is insulin resistant, so it's shooting free fatty acids into all the organs.
So when we tackle these patients, we want to start early on. At the core of the problem, there is that increased adiposity. So that's why I think GLP-1 and other duos or triples are kind of the backbone of pharmacological management of these patients, because we have the liver benefit, but we have all the other benefits of achieving weight loss. And then we have other more organ-specific therapies that we may need. If they have more kidney disease, we may be thinking about SGLT2s, finerenone, or ACE inhibitors and ARBs for kidney protection. If they end up having more liver disease, we have more liver-directed therapies, and we will have even more medications coming.
So we will start to think about combination therapies for the organs that they have most of the damage on. But we really want to start early on treating that increased adiposity and achieving significant weight loss, because then we'll get all the benefits across all the organs.
Announcer:
You just heard Dr. Fernando Bril sharing his expertise on obesity and liver disease treatment. To access this and other episodes in our series, visit GI Insights on ReachMD.com, where you can Be Part of the Knowledge. Thanks for listening!