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Prof Michael Nauck: GLP-1 receptor agonists and type 2 diabetes

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GLP-1 receptor agonists and glycemic control in patients with type 2 diabetes

 

 

 

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Clementine:

Hello! You’re on MD-FM INSIGHT, the first medical web radio. Today we’ll be devoting our "Question & Answer" program to the treatment of type-2-diabetes with glucagon-like peptide 1 receptor agonist.


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Clementine:

At the last meeting of the American Diabetes Association, in Chicago, we interviewed Dr. Michael Nauck, from Bad Lauterberg Hospital in Hartz, Germany, who presented the results of three phase III trials on a new investigational, long-acting glucagon-like peptide 1 receptor agonist, which is being studied as a once-weekly treatment for type-2-diabetes. Listen to our conversation with Dr. Nauck:


Clementine:

So Dr. Nauck, you presented 3 studies on this new GLP-1 receptor agonist called dulaglutide.. There are many molecules in this class now –how do differentiate them, how use them…?


Nauck-1: “Dulaglutide is typical of the long acting GLP-1 receptor agonists that only have to be injected once every week. And you maintain a steady high concentration of the agonist so you have a constant binding to GLP-1 receptors, and that differentiates this group from the short acting GLP-1 receptor agonists and, to give a name, exenatide, and lixisenatide, are representative of this class, which after injection, peak after two hours and then, they reduce their plasma concentrations so that, with one or two injections a day, you have some periods where the organism is exposed to the drug, and other periods, like the night, when there is very low levels --even approaching zero concentrations. So it’s an on/off mechanism and that seems to be necessary in order to preserve the acute effects on decelerating gastric emptying, which you do not observe during long-term treatment with the longer acting GLP-1 agonists.”


Clementine:

And when you decelerate gastric emptying –what does that lead to?


Nauck-2: “If you decelerate gastric emptying, that gives you a very prominent effect: preventing post-prandial hypoglycemia. So you almost have a flat line in your glucose profiles when you inject a short-acting GLP-1 receptor agonist. Because of that, they are most suitable when you combine them with a long-acting basal insulin because then, the insulin takes care of the fasting and pre-meal glucose concentrations, and the short-acting GLP-1 receptor agonist takes care of the post prandial rises.”


Clementine:

Whereas the long acting GLP-1 receptor agonists…?


Nauck-3: “The long acting GLP-1 agonists are better suited for the combinations with oral glucose lowering agents because they expose the patients to the active drug during the night, which gives you a better reduction in fasting glucose and, even though they are slightly worse on post prandial glucose, the net effect is a better reduction in HbA1c.”


Clementine:

Ok and how do you compare GLP-1 receptor agonists and DPP-4 inhibitors?


Nauck-4: “Well the common thing about DPP-4 inhibitors and and GLP-1 receptor agonists is that they are both derived from the incretin system. Although they work through different mechanisms. Clinically speaking, I think we have seen lots of head to head comparisons, like the dulaglutide study comparing to sitagliptin, that clearly show, if you need great reductions in HbA1c, then you are better off with a GLP-1 receptor agonist. On the other hand, they need to be injected, DPP-4 inhibitors can be given as an oral drug. So most patients know what they need and what they prefer. So I very rarely am tempted to give both in the same patients. I think it is very obvious in the clinical situation which one to choose.”


Clementine:

And there have been reports of incretins being associated with possible cases of pancreatitis… what do you think about this data?


Nauck-5: “So what is known is that cases of acute pancreatitis occur in patients treated with incretin-based drugs –both DPP-4 inhibitors and GLP-1 receptor agonists. What is not known is whether the probability of seeing that is higher when the patient is treated with incretin-based drugs. There are some studies suggesting that yes, you have an elevated risk, but these studies have methodological faults and cannot be taken as a final proof that this is the case. There are animal experiments in addition, and the majority of them do not show any damage to the pancreas that would be compatible with an elevated risk.”


Clementine:

So do you have a final answer…?


Nauck-6: “I believe we cannot give a final answer right now, we need more information, but we will get more information because there are a number of outcome studies with between 6000 and 16000 patients treated with such agents, and followed up for two to seven years, and we should know about an elevated risk of pancreatitis after analyzing these studies. As far as I see it, the companies have made a commitment that they give away all this information to an academic group looking exactly at that, so that the results will be pooled and we will probably be able to narrow down the risk with relatively short confidence intervals, after these studies have been analyzed.”


Clementine:

So what is your take home message?


Nauck-7: “We have new GLP-1 receptor agonists, so that now we can classify them into short acting and long acting ones. We have GLP-1 receptor agonists which have a very profound effect so they can compete with insulin, when a type-2 diabetic patient needs an injectable treatment. Some of them may be associated with the risk of nausea and vomiting, others are free from that, like albiglutide, results have been presented at this conference… So we will have a choice of different agents, so it’s much more likely that in the future we will to pick the right compound for the right patient and that more and more patients will be treated with these agents.”


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Clementine:

This show is over. By visiting the MD-FM website, you can check out the themes of the programs we will be offering you regularly.


 See you soon on MD-FM.

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