Updates on Treatment Options in the Modern Management of Diabetes

CARLOS R. HAMILTON, JR., MD, FACE: Hello, I'm Dr. Carlos Hamilton and welcome to the AACE Clinical Conversations. In this program, we will discuss updates on treatment options in the modern management of diabetes.

Joining me today is Dr. Brian Tulloch, Clinical Associate Professor of Medicine at the University of Texas Medical School at Houston and endocrinologist at the Diagnostic Clinic of Houston.

Also with us is Dr. Naveed Iqbal, a fellow in endocrinology at the Baylor College of Medicine.

We all know that our patients, especially those with type 2 diabetes, when we start off by giving them information about lifestyle modifications and we start them on oral agents, sooner or later, these oral agents are going to prove to be inadequate in the management of their disease.

At what point does one consider going on to other agents Brian in the management of these cases?

BRIAN TULLOCH,MD: Carlos, I think what really matters here is when the patient understands we are in trouble because I start off by telling him he is a team. He and I are in this together.

So if we've trained him properly, he'll already be beginning to think there is a problem when his glyco goes much above 7% and certainly when it's above 8%. And by the time it's 8.5%, we both agree that even no matter what his objections are, we need to do something else.

CARLOS R. HAMILTON, JR., MD, FACE: So you have the options of going either to insulin at that point, or in some cases, to some of these newer agents, some of these new peptide and other compounds that have resulted from our understanding of the pathophysiology of glucose metabolism and diabetes.

Tell us a little bit about some of those, especially the exenatide drug.

BRIAN TULLOCH, MD: Carlos, this is an exciting time to be in diabetes. I love to make a little humor in a situation like this because exenatide is something they have never heard anything about, even our colleagues in family practice haven't heard about this stuff.

On the wall I have a picture of a stomach, and beside it is a picture of a pancreas. And I explain to the patient that his stomach used to talk to his pancreas and say, "Wake up and make a little insulin. I am not full of food."

So I think go back and I also have a picture of a Gila monster on the wall. I point to this thing and said, "This thing eats one day every four months, so for three months and 29 days the pancreas is asleep, and on the 30th day of the fourth month the pancreas is woken up by a message. What you have access to is the message from the Gila monster's salivary gland, and that's going to wake up your pancreas."

CARLOS R. HAMILTON, JR., MD, FACE: You don't tell the patients that they're going to be on a diet or they're only going to get to eat every four months?

BRIAN TULLOCH, MD: I promise them if they were a Gila monster, they would get one rat every four months.

CARLOS R. HAMILTON, JR., MD, FACE: All right. Okay. Well, that will make them thankful. [LAUGHTER] So you've had some experience with exenatide. Tell us a little bit about it.

BRIAN TULLOCH, MD: Useful stuff. It really does work. Interesting because when a patient's type 2 diabetes is getting to the stage where the orals don't work, the original concern was, "Gee doc, I don't want any shots," or "My grandmother had such a bad experience," whatever.

They've read a little bit about this stuff, and their neighbor's been on it. They've seen their neighbor get a wee bit smaller. And so it's interesting, they come in saying, "Doc, what about that new stuff? What about that Gila monster, whatever it is?"

And this makes it easy. Because that means not one shot, but two shots a day. But if it's going to help them get their sugar down, and above all, 85-95% of our type 2 diabetics are also obese, if it's going to help him with his weight, he's happy to give it a try.

CARLOS R. HAMILTON, JR., MD, FACE: Certainly, my experience would be that the prospects of helping them lose weight is a great motivator and people are often welcome to give it a try. But when they do try it, have you had good results with it? Has it actually lowered their hemoglobin-A1c?

BRIAN TULLOCH, MD: Like everything else that's new, one has to monitor or modify their expectations. Some people have had wonderful weight loss. In fact, I have a colleague who had a patient come down 55 pounds.

On the other hand, at the other extreme, there are patients who get so much nausea with even 5 mcg, they can't take it. So one has to sit down and explain that the message to the pancreas to wake up and make a little more insulin is also the message of satiety that the stomach sends to the hypothalamus to say, "I'm full. Don't eat anymore," and that in some patients, that satiety message is read as nausea.

And so that helps them modulate their expectations so that when they've had this first shot, if they get a little bit nauseated, they already are expecting that and that they won't be promised a rat after four months. They will get a choice of whether to go up to 10 mcg or whether to stay at 5.

I've had a number of folk who were quite okay on 5 mcg, but the nausea problem became a 10.

CARLOS R. HAMILTON, JR., MD, FACE: Yeah, I've had that same experience. But it is certainly true that some people respond extremely well to Byetta, and other people just simply cannot tolerate it.

BRIAN TULLOCH, MD: Right.

CARLOS R. HAMILTON, JR., MD, FACE: Naveed, you've had some experience with the new drug Januvia. Tell us a little bit about the DPP-4 drugs and what your experience has been.

NAVEED IQBAL, MD: Just as Dr. Tulloch mentioned, it's a very exciting time to be in diabetes field. The reason for it -- one of the reasons for it is the DPP-4 inhibitors. What they do is the concept is very similar to Byetta or exenatide.

What exenatide does it is gives large doses of GLP-1, which cannot be broken down by DPP-4 inhibitor. So twice a day you reach the concentrations which are like 10 to 15 times the normal, and then they gradually come down.

In Januvia, what happens is it uses the human GLP-1. We do not give any GLP-1 externally, but we give the DPP-4 inhibitor. This inhibitor is needed to break the GLP-1 down.

Since we inhibit the enzyme, we see the concentrations are usually about three to four times of -- like normal controls. And this higher concentration helps with a couple of things.

The higher concentration of GLP-1 or the incretins help with reducing the release of glucagon after a meal. That is one of the major problems in diabetics because when the glucagon is released after a meal, the blood sugars go further high, and that can be a problem in diabetics, whereas once the GLP-1 levels are higher, then they do not come across.

The problem is not as bad. Like their postprandial blood sugar excursions are not that high.

The second agent -- actually DPP-4, it also acts on GIP, that is the gastric inhibitory peptide, and it breaks that down also. If we inhibit the DPP-4, that's going to stay longer also.

And the cumulative effect is multifactorial. What happens is these agents act centrally and tell the person that you are full, you shouldn't be eating anymore. The gastric emptying is slowed down.

That produces a sensation of satiety, which can be useful for these patients, and also GLP-1 -- one of the most important things with GLP-1 is that it senses the high blood sugar levels and it releases the release -- it increases the release of insulin. That is very useful with that.

But that is sort of blood sugar-dependent, so it does not cause hypoglycemia.

Also, another thing I would like to say about these DPP-4 inhibitors is that the most common problems which the type 2 diabetics face is the weight gain or the hypoglycemia. These are major barriers to improving the control. There are so many agents out there. Still there are so many patients who haven't reached their goal.

The reason for that is twofold, the hyperglycemia as well as the weight gain. The weight gain is more of a problem for type 2 diabetics. And agents like exenatide and Januvia are very good in that sense.

Byetta can cause a lot of weight loss, which is the brand name for exenatide, and Januvia is useful in the sense it does not cause weight gain.

If you compare Byetta and Januvia, the problem with Byetta is that it's an injectable. Januvia is oral. And the other good thing with Januvia is that it does not cause nausea, whereas Byetta does.

There is no weight loss with Januvia, so some of the people, they don't like the needles. You can go with Januvia.

CARLOS R. HAMILTON, JR., MD, FACE: So these two agents, and actually perhaps even some others are an important adjunct in the management of type 2 diabetics that have failed to respond adequately to the first line drugs.

At some point, most people feel that type two diabetics need insulin. Brian, how do you -- what do you feel about that and at what point do you suggest patients going on insulin?

BRIAN TULLOCH, MD: Carlos, that's another exciting area. Again, I try to have my patients so monitoring their own conditions that they know when the glycohemoglobin is starting to creep up and we tried everything, that poor old pancreas in there is needing to have a little bit of external assistance.

By that time, they're not resentful of the fact that this shot of long-acting insulin, which they'll take once-a-day, is going to be helping their pancreas. We've already introduced them to that concept. So it's an assistance...

CARLOS R. HAMILTON, JR., MD, FACE: Very good.

BRIAN TULLOCH, MD: ...rather than threat. And then I have a diagram on the wall which shows the differentiation between the short-acting insulins, which are the new log insulins, the inhaled insulin, and the long-acting insulins, of which Lantus is an example, and a newer one made by Novo is Levemir, is the second. So we have those two options ahead.

I give them the option of a once-a-day insulin. I give them the insulin of night or morning, and there is data to be said pro or con either of those. And we set out -- he and I are part of the team and he is the main component. I'm his assistant. And we set out to find out the right dose of long-acting insulin to bring his fasting sugar down to what's euglycemic.

Everyone has a circumstance when they're going to need a little more insulin than what they have onboard, and perhaps some of the short-acting insulins might be very helpful, even in a person that doesn't need short-acting insulin, but on occasions. And perhaps this is where some of the inhaled insulins might be useful in type 2 diabetics that are, say, receiving Levemir or Lantus, but they know they're going to birthday cake experience, and they might find that to be a useful adjunct.

BRIAN TULLOCH, MD: Carlos, that's ideal. That's just the way one does it. You bring in the long-acting and short-acting insulin as their assistant to help them improve their quality of life.

One small issue when you're thinking about insulin is for the guys who make a living from driving and flying. That's the one absolute line which really they will say goodbye.

If you have a public pilot or a public driver, once they go on insulin, pretty well they lose their licenses. That doesn't apply to the private flyer or the scuba diver. Again, there have been rules that have been modified over the last 10 years that allow an individual airline flyer to fly himself, even though he's taking insulin and a scuba diver to scuba dive, again, even though he's taking insulin.

But it's a very important issue. One has to be proactive with those guys who are driving and flying professionally.

CARLOS R. HAMILTON, JR., MD, FACE: And even those that do these certain activities when they're taking insulin, it's -- you know, what the rules are may be one thing, but what the patient does day in/day out is strictly a matter of checking your sugar and adjusting your treatment and your food intake appropriately to accommodate the circumstances.

BRIAN TULLOCH, MD: By that...

CARLOS R. HAMILTON, JR., MD, FACE: Generally, people can live a full life without any restrictions if they do these things.

BRIAN TULLOCH, MD: Absolutely. And also by that time, he's aware that if he's flying his own plane, his life depends on maintaining euglycemia. So he has his home glucose monitor with him. He has the ability to raise or lower his sugar right sitting there in the cockpit with him. So that's very important.

But it does take up the challenge, which we have given ourselves, which is to allow a type 1 and a type 2 diabetic to live a perfectly normal life.

These days, there are certain newer agents like inhaled insulin, and it can be useful in the patients who do not want to inject themselves at all or want to do it as few number of times as they want. And they could just get Lantus one injection every night to produce -- to provide the basal insulin, and they could take the inhaled insulin to avoid the further three shots. They could just take it with each of the meals.

CARLOS R. HAMILTON, JR., MD, FACE: That certainly would be an ideal circumstance and use for that particular agent, yes.

NAVEED IQBAL, MD: But there is another problem with that. The pump right now is pretty big, so most of the patients do not opt for it as far as like it's pretty rapidly absorbed, like NovoLog or aspart. So it acts rapidly, but the device is so big that some of the patients do not want to take it around with them.

Another thing about -- my favorite agent is Lantus, and with that I usually use NovoLog. I think it is much easier to titrate blood sugar in those because you can just put the patient on one Lantus shot and NovoLog with each meal, as opposed to MPH, which has got peaks and valleys -- with that hypoglycemia -- I feel it's more of a problem.

CARLOS R. HAMILTON, JR., MD, FACE: I think most of us would agree with you, and I think the bottom line is that we do have a lot of options and that working with the patients, and as Brian said, making sure that it's a team approach with the patient as the quarterback of this team, is -- is an important part of it.

But again, I want to thank both of you for being with us today. And again, I'm Carlos Hamilton, and thank all of you for watching.