SGLT2 Inhibitors: A Discussion Beyond Just the Glycemic Benefits - Episode 1
A Review of the Current Diabetes Treatment Landscape
Troy Trygstad, PharmD, MBA, PhD; Javier Morales, MD, FACP, FACE; and Dhiren Patel, PharmD, examine the current treatment landscape for the management of diabetes.
Troy Trygstad, PharmD, MBA, PhD: Hello. Thank you for joining this Pharmacy Times® Peer Exchange® panel discussion. Type 2 diabetes mellitus is a progressive disease with multiple underlying pathophysiologic defects. Most often, monotherapy cannot maintain glycemic control, and a combination of glucose-lowering agents is used. Pharmacists are increasingly taking on a provider role in educating patients on their therapy options to ensure adherence. This Peer Exchange* will explore the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors to treat type 2 diabetes mellitus. We will also review when to use them, highlighting their benefit as monotherapy and in combination therapy.
I am Dr Troy Trygstad, and I am the vice president of pharmacy and provider partnerships for Community Care of North Carolina in Raleigh, North Carolina. I’m also the editor-in-chief of Pharmacy Times®.
Participating today on our distinguished panel are: Dr. Tripp Logan, vice president of L&S and Medical Art pharmacies in Charleston, Missouri. He’s also a partner with MedHere Today in Nashville, Tennessee. We also have Dr. Javier Morales with us. He is an associate professor of medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell University and vice president of the Advanced Internal Medicine Group in East Hills, New York. And finally, we have Dr. Dhiren Patel, associate professor of pharmacy practice at MCPHS (Massachusetts College of Pharmacy and Health Services) University and clinical pharmacy specialist at VA Boston Healthcare System in Boston, Massachusetts. Thank you all so much for joining us. Let’s begin.
Dr. Morales, can you give us an overview on the currently available drugs for the treatment of diabetes?
Javier Morales, MD, FACP, FACE: That’s actually a pretty broad question. There are so many different agents that we have at our disposal for use. If we look historically, I think the first agents that actually became available were those in the sulfonylurea class, and then, subsequently, metformin came in.
Then there was this incredible snowball of new agents that have become available for the management of diabetes. What’s kind of interesting is that they each have their own particular profile in regard to how they work, from a mechanistic standpoint. One thing that we’ve learned is that there are core defects that have been described as creating the pathology of hyperglycemia. These were termed as the “ominous octet.” When we look at the different components of the ominous octet, some of these agents that we use for the management of diabetes do target some of these things, so, let’s take a look at a couple of them in particular.
The first one I’d like to mention is going to be the incretin effect. The incretins are a specific class of agents that are centered around a naturally produced peptide out of the intestinal L cell, called glucagonlike peptide 1 (GLP-1). Unfortunately, its life span is limited to about 2.5 minutes because of a ubiquitous enzyme called dipeptidyl peptidase—4. These agents are actually quite nice. In addition to offering good blood glucose control, they do not tend to create low blood sugar reactions or weight gain that could be seen with intensification of therapy.
Then we have another class of drugs that became available more recently, called the urinary SGLT2 inhibitors. In our kidneys, we actually have several receptors that are important to the absorption of glucose once we eat. These receptors are called the GLUT2 cotransporters and the SGLT2 receptors.
For most individuals who do not have diabetes, we will never see glucose in the urine. These receptors are responsible for reabsorbing glucose, so in a nondiabetic individual, you probably won’t see glucose in the urine unless you start to surpass about 160 or so. However, it’s kind of interesting—in patients with type 2 diabetes, you won’t see glucose in the urine until they surpass at least 220. Part of the reason for this is because there tends to be an upregulation of these GLUT2 and SGLT2 receptors, so the kidney is indeed part of the core defect of hyperglycemia.
Fortunately, a drug became available in the 1800s. This was actually the first described agent that would block the SGLT2 receptor. Historically, it was put on the back burner because a group of physicians felt that if it made you pee out sugar, then it couldn’t be good for the kidney, but since that time, it’s resurfaced. It’s been reexplored and validated as a useful class of drugs to use for the management of type 2 diabetes.
Dhiren Patel, PharmD: To add to what you were saying, it now hits a core defect that it previously never hit, right? That was the missing core defect that none of the other previous classes hit. Now we have something that can specifically hit that core defect for the kidneys.
Javier Morales, MD, FACP, FACE: Absolutely. So, it’s evolved. Today we have several in the marketplace. We have dapagliflozin, canagliflozin, and empagliflozin. More recently, ertugliflozin was approved into the marketplace. And then we also have some newer agents in the marketplace that look at SGLT1 inhibition, as well. These agents actually work very, very well. They block those receptors that are responsible for reabsorbing glucose at the level of the kidney. So, seeing glucose in the urine in patients who are using these agents is actually quite expected. It sets up a little bit of a question mark, as well, particularly for those who might be employed in civil service jobs—like airline pilots or bus drivers or train operators. They obviously have to go for their health screening. I’ve seen so many patients who are on these drugs who have come to me and have said, “Oh, look, they’re not letting me work anymore because they say I have uncontrolled sugar or diabetes. I have sugar in the urine.” So, if using that class, I think it’s important to take that into consideration.