When Insulin is Needed in Type 2 Diabetes

Carol Wysham, MD: In the EMPA-REG study, it’s estimated that the people that were in that study comprised only about 16% of our patient population. So, let’s sit down and talk about the other 84%. When we’re talking about the options, you can sit down with a patient and talk to them about the pros and cons of the different therapies, and it doesn’t take more than about 2 minutes. Almost everybody that can afford it will be focusing on the agents that help them with their weight.

Julio Rosenstock, MD: In the other 84%, a lot of those people have unrecognized cardiovascular disease.

Carol Wysham, MD: I am just explaining that if you are going to restrict those therapies for patients with cardiovascular disease, that you’re missing 84% of your patients—some of which, yes, are going to have unrecognized heart disease. But when you focus on the different options for patients and allow them to help make the decision, they understand. They understand that there’s options and that if this doesn’t work, that they have side effects with this, they know that they can come back and say, “This didn’t work for me.”

Vivian Fonseca, MD: I agree with Carol. Those 84% may have unrecognized heart disease, but they were not included in the trial. And those trials are going on.

Julio Rosenstock, MD: I know, for sure, that metformin and an SGLT2 (sodium-glucose co-transporter-2) will give you weight loss, will not give you hypoglycemia, will reduce your blood pressure, and so on. I want to see studies being done in people with risk.

Vivian Fonseca, MD: They are being done.

Peter Salgo, MD: They’re done.

Carol Wysham, MD: They’re done. They just haven’t been reported yet. We’re going to have them in June.

Peter Salgo, MD: The job is not finished till the paperwork is done.

Carol Wysham, MD: Yes, the paperwork isn’t done.

Peter Salgo, MD: That being said, we’ve been talking about weight. Now, I remember some of these drugs, early on, had weight loss reported with them. We were all cautioned regarding the weight loss component. It may be ephemeral; it may not be significant. But you’re telling me, in fact, it is significant. Is weight a significant issue when you start prescribing these drugs?

Vivian Fonseca, MD: It’s a huge issue for the patients. I think it’s ironic. You tell somebody, “You need to be losing weight,” and you give them a prescription or a drug that makes them gain weight. That’s just contradictory.

Carol Wysham, MD: It’s cruel.

Vivian Fonseca, MD: Yes, and then they feel guilty coming back with weight gain. So, if someone is struggling with weight and wants to lose weight, choose a drug that will cause weight loss. Although Julio says that SGLT2 inhibitors are good for this, there are better ones. GLP-1 (glucagon-like peptide 1) receptor agonists are far better at weight loss—not in everybody, but in a significant number of people.

Julio Rosenstock, MD: Yes.

Robert Henry, MD: Weight is really important, but preventing weight gain is what we’re doing. We’re not inducing huge weight loss. With any of these medications, you’re getting about 2%, 3%, 4% body weight loss with benefits, but not dramatic benefits. What you’re preventing is the natural history of weight gain that occurs in almost all patients with diabetes. When you use agents that accelerate weight gain, then you have a disease that is already prone to obesity or weight gain and you’ve accelerated that.

Julio Rosenstock, MD: But we’re talking about noninjectables, and with the noninjectables, the only one that gives you weight loss is an SGLT2 (and is very consistent). You have a loss of calories; it has a glycosuric effect. You lose 60 to 80 g of calories, so you’re in a negative balance of 200 to 300 calories a day. We’ve seen study after study after study of losing 2 kg that is sustained, which is important.

Peter Salgo, MD: Tell me about hypoglycemia. You alluded to it, you all did. How does the risk of hypoglycemia impact this decision with all these agents? Where do we go with this?

Robert Henry, MD: I think preventing hypoglycemia is extremely important. I think that in the oral agents, most of us have been trained with sulfonylureas. Especially, with the early sulfonylureas, there was horrible hypoglycemia. But if that’s all you had, that’s all you had. They got better over time with some of the second-generation sulfonylureas. But now, being able to use agents that are as effective or more effective, perhaps in multiple areas, has been beneficial. You don’t have to worry about the low blood sugars in these patients. You can tell them, very confidently, that they may have a blood sugar of 65, but that’s not going to hurt them.

Julio Rosenstock, MD: And it is true. Let’s be fair with the sulfonylureas. I’m sure that it’s been given a bad image, but if you use a low dose of glimepiride or glipizide and you have a normal renal function, I they’re not that bad. We’re actually doing a study where we’re comparing glimepiride versus linagliptin—that is the CAROLINA trial that is going on for 5 or 6 years—that is going look at the cardiovascular events. That’s the other issue of the sulfonylurea: the effect on cardiovascular disease.

Carol Wysham, MD: Getting back to your question on hypoglycemia. I actually think there’s 2 issues related to hypoglycemia. One is how often it occurs and how often it’s recognized. And the problem is that most providers fail to ask patients about hypoglycemia, and most patients either don’t recognize their hypoglycemia or feel it is the price to pay. Providers have no idea how frequently their patients are experiencing hypoglycemia. The patients are experiencing it, and they are likely doing whatever they can to avoid hypoglycemia. They don’t take as much medication, they eat bedtime snacks when they don’t need to have snacks. So, I think hypoglycemia is the biggest barrier for treating our patients aggressively when we’re using agents that put them at risk of hypoglycemia.

Transcript edited for clarity.