DPP4 inhibitors and incretin mimetics

We don't use them together. And the newly released guidelines suggest that they should not be used as part of the same regimen.

habeansha said:

No one seems to be able my question. But can you use a DPP4 inhibitors (Januvia/Onglyza/Tradjenta) together with a incretin mimetic (Byetta/Victoza)?

I've never seen it on any of my rotations, but encountered an RxPrep question with the scenario, not pertaining to the question. I've also had doctors claim that they do the same thing, ones just oral and ones SQ.

In my mind i would think using both together would result in longer duration of action of incretin, but is there a reason not to use it?

sorry if this is a stupid question

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How often are you going to encounter patients going on both anyway? These give marginal improvement on A1c and are 3rd or 4th line agents. If patients are going to stick themselves, they probably should be on insulin.

xiphoid2010 said:

How often are you going to encounter patients going on both anyway? These give marginal improvement on A1c and are 3rd or 4th line agents. If patients are going to stick themselves, they probably should be on insulin.

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Newest guidelines have both classes as potential 2nd line agents when something is needed as add on to Metformin. But guidelines also don't recommend using DPP4 and GLP1 together.

I'm referring to the ADA/EASD position statement that was published 4/19.

All4MyDaughter said:

Newest guidelines have both classes as potential 2nd line agents when something is needed as add on to Metformin. But guidelines also don't recommend using DPP4 and GLP1 together.

I'm referring to the ADA/EASD position statement that was published 4/19.

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Took a quickly look. Interesting. Thanks. How quickly things changes in just a year if you don't use it. I wonder if VA is modifying their algorithm as we speak. When I was there, it was metformin --> sufonyl urea --> basal insulin or TZD --> insulin. DPP-4 inhibitors and GLP-1 were extremely rare, they only gave ~0.5 improvement on A1c and just not cost-effective.

I wouldn't think it's a good idea to use them together. Dpp4 give you a 3-4x increase in your endogenous incretins, just from them not being broken down. With the mimetics, you're getting 100x increase by directly adding more, which is why you have higher incidence of n/v, delayed gastric emptying, and increased satiety with those agents. Seems that combining them would just lead to a level that's much too high.

xiphoid2010 said:

How often are you going to encounter patients going on both anyway? These give marginal improvement on A1c and are 3rd or 4th line agents. If patients are going to stick themselves, they probably should be on insulin.

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There are a few interesting studies on Type I patients and Byetta, check those out.

An important question to ask is: Does using Metformin + DDP-4 inhibitor ($8.50/day) produce better outcome than Metformin + Glipizide (10 cents/day)? What is the incremental cost-effectiness ratio (ICER)?

When looking at treatment options from a higher level (health system, PBM, governmental agency), cost-utility of each option should be compared.

xiphoid2010 said:

An important question to ask is: Does using Metformin + DDP-4 inhibitor ($8.50/day) produce better outcome than Metformin + Glipizide (10 cents/day)? What is the incremental cost-effectiness ratio (ICER)?

When looking at treatment options from a higher level (health system, PBM, governmental agency), cost-utility of each option should be compared.

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In my clinic we might prefer the DPP4 over the SU in an elderly patient for whom hypoglycemia is more risky or in a patient for whom we'd like to avoid weight gain. Of course, the patient has to be able to PAY for the more expensive drug.

You mentioned the VA world... kind of expect metformin + SU to remain first line. Don't you?

All4MyDaughter said:

In my clinic we might prefer the DPP4 over the SU in an elderly patient for whom hypoglycemia is more risky or in a patient for whom we'd like to avoid weight gain. Of course, the patient has to be able to PAY for the more expensive drug.

You mentioned the VA world... kind of expect metformin + SU to remain first line. Don't you?

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That, or Metformin + GLP-1 (Byetta) for weight loss

All4MyDaughter said:

In my clinic we might prefer the DPP4 over the SU in an elderly patient for whom hypoglycemia is more risky or in a patient for whom we'd like to avoid weight gain. Of course, the patient has to be able to PAY for the more expensive drug.

You mentioned the VA world... kind of expect metformin + SU to remain first line. Don't you?

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Very much so. The VA is very good at providing the standard of care the cheapest way possible. I wonder though if they will loosen up the restriction a bit more now due to the new guideline. But then again, VA also publishes its own guidelines.

The thing with expensive medication is that unless the patient is paying for the entire price of the drug, a large cost is still being passed onto the healthcare system and the society. This is not to say these drugs don't have a place in therapy, it is just that they should be restricted to those patients it is cost-effective.

xiphoid2010 said:

Very much so. The VA is very good at providing the standard of care the cheapest way possible. I wonder though if they will loosen up the restriction a bit more now due to the new guideline. But then again, VA also publishes its own guidelines.

The thing with expensive medication is that unless the patient is paying for the entire price of the drug, a large cost is still being passed onto the healthcare system and the society. This is not to say these drugs don't have a place in therapy, it is just that they should be restricted to those patients it is cost-effective.

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I would expect that once the secretagogues have tapped out the pancreas that they'd gave to transition to a different pathway for treatment.

Farmercyst said:

I would expect that once the secretagogues have tapped out the pancreas that they'd gave to transition to a different pathway for treatment.

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Yes, it's usually is replaced by NPH, produce similar profile and is very cheap.

VA is a very interesting system of how pharmacist can play a much bigger role. They give clinical pharmacists prescribing rights to manage much of ambulatory care patients. Pharmacists are also charged with studying cost effectiveness and given much power in guarding the formulary. I wonder just how much net saving this system produces.

This might be an good model for the expansion of pharmacy profession into the future, but there will be much legal hurdle on the non-federal level.

xiphoid2010 said:

Yes, it's usually is replaced by NPH, produce similar profile and is very cheap.

VA is a very interesting system of how pharmacist can play a much bigger role. They give clinical pharmacists prescribing rights to manage much of ambulatory care patients. Pharmacists are also charged with studying cost effectiveness and given much power in guarding the formulary. I wonder just how much net saving this system produces.

This might be an good model for the expansion of pharmacy profession into the future, but there will be much legal hurdle on the non-federal level.

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thanks God others don't follow VA model. Otherwise, there won't be any new drug

Angryrooster said:

thanks God others don't follow VA model. Otherwise, there won't be any new drug

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Or drug companies will have to work on drugs that actually provide significantly better outcomes for once. The ability of the society to shoulder medical cost for the benefit of the pharmaceutical industry is limited. Pharmcoeconmics will only become more important as new drugs keep on getting more expensive. Remember Xigris and Avastin?

Having said that, VA does allow non-fo or more expensive formulary agents. You just need to provide clinical justification that will stand up to a clinical pharmacist review.. If it's only for lower risk of hypoglycemia or a few pounds weight, he is probably going to tell you to dose and educate the patients better. On the other hand, if you have done all that and documented it, it would probably get approved.

habeansha said:

No one seems to be able my question. But can you use a DPP4 inhibitors (Januvia/Onglyza/Tradjenta) together with a incretin mimetic (Byetta/Victoza)?

I've never seen it on any of my rotations, but encountered an RxPrep question with the scenario, not pertaining to the question. I've also had doctors claim that they do the same thing, ones just oral and ones SQ.

In my mind i would think using both together would result in longer duration of action of incretin, but is there a reason not to use it?

sorry if this is a stupid question

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To answer your question all you have to do is look at how they work. Technically you can use them together but why should you? DPP4 inhib. prevent the breakdown of GLP while the incretin mimetic are GLP agonist.They both do the same thing just in different ways so it wouldn't be best to use them together.

Pharmpills said:

To answer your question all you have to do is look at how they work. Technically you can use them together but why should you? DPP4 inhib. prevent the breakdown of GLP while the incretin mimetic are GLP agonist.They both do the same thing just in different ways so it wouldn't be best to use them together.

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+1

In general a good rule of thumb for most pharmacotherapeutic situations is to use agents that act via different mechanisms of action for a certain indication (ie: CCB/Thiazide with ACE-I/ARB/Beta blocker in hypertension).

There was a head to head study with liraglutide vs sitagliptin with both arms on metformin. Likewise, in the PI for Victoza it shows it to be superior to Byetta in a1c reduction.

www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60307-8/abstract