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Choice of DPP IV i – Evidence to date – Dr Shruthi Chandrasekar

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Diabetes Dialogues Discussions – 3D Conference

And it’s a lot of patience and also in post-transplant and she is going to talk on joyce’s before evidence to date thank you dr. pitchman it was a kind introduction thank you so what i’m going to be doing for the next 15 minutes or 10 minutes is a timer so 10 minutes or so is the talk on the evidence to date on dpp-4 inhibitors specifically focusing on linagliptin

So what i will not be doing is comparing different lipton’s or dpp-4 to other class of agents so this is the introduction i’m going to give you the overview of different agents that have come over the past from 1950s to no sulfonylurea available in 1990 we recently celebrated 20 years of sulfonylurea and then with dp before with dp before now we know that we have

Data for the past 10 years right with satar lipton being first so we have enough data with dpp-4 inhibitors so the question always comes when our practice what next after metformin right to me every single drug including sulfonylurea at t cds dpp-4 glp-1 receptor sglt2 inhibitors and basal insulin have a role of what comes next right but what i am going to be

Specifically talking for the next nine minutes is giving you some sort of fascinating evidence with linagliptin as a molecule right what what are the newer evidence that has come out with energy lipton which i sort of learned while i was preparing for this talk i should really thank dr. g dk for gleaming this opportunity to sort of learn while i was preparing for

This talk so if you also have to go by the recent a da esd guidelines it is a very nice guidelines you would have all seen this where we have a patient-centric management whether you have a heart failure pre domination or a ckd or taking cost into consideration of your patient so you can actually choose the drug depending on your patient’s condition right what i

Think should also be included in the algorithm is liver disease we had an excellent presentation of nash and non-alcoholic fatty liver disease i think we have seen a whole lot i mean in our liver institute we see a whole lot of patients with nafld and diabetes so i think we should also have an algorithm specific to patients who have liver disease right so that is

Not there but apart from there all the this is a very nice patient centric algorithm that we can actually follow in our clinic so in spite of all these things we still have numerous challenges when we have to get the hba1c under control it could be age compliance the sustainability of the drug comorbidities hypoglycemia weight you know you can you can go with all

These things could be the reason why we are not able to get hba1c under control so what we need is a glucose lowering agent that is has enough data for good glycemic control because that is exactly why we use these agents weight neutral low risk of hypoglycemia of course know those adjustment required in conditions of renal disease liver disease even be used in

The post transplant setting so that safety of that molecule is very important to us cardiovascular safety and renal safety so with this we all know we had a very nice talk by dpp-4 inhibitor by dr. don answer in the morning session so we all know how dpp-4 inhibitors work and i still i’m having very less time to present my date i’m going to skip these slides here

So the most important point the 10 points about in critten is they are insulin secretion enhances two nutrients right so it is an insulin secrete agog but works in a different mechanism through incretin pathway unlike sulfonylurea which acts in the direct potassium channel in your pancreas it’s once daily oral preparation low risk of hypoglycemia you know we have

Always talked about weight gain and hypoglycemia and i’m sure majority of us know this point we have data for preserved you know betta selma’s it complements metformin sglt2 which is what krishna is going to be talking on how you can use this molecule as a co molecule you know combining with sglt2 in your practice office pleiotropic effect not that much as an sglt2

But we do have some data with blood pressure control especially with say doug leighton and some of these drugs in trials have actually even shown a subtle weight loss even though we call it generalized as weight neutral safety in elderly we have emerging studies coming out in patients with cognitive functions emerging cardiac and renal data which i’ll quickly run

Through and overall we all know for the past ten years we have been using dpp for it so overall a very safe molecule to start with so when we were actually this is exactly what i told you so when we are in a forum where they were actually comparing this to actually this bike which was introduced few years back with the tag line of just set and go that’s exactly

What we have been doing with dpp for you just started we know it works we know the durability we know the overall safety profile you know so it’s probably would actually suit this jet set go tagline which was actually sort of introduced when this onda bike came into the market and with linagliptin what we know is sustained 24 hour true control through inhibition

Of dpp for enzyme and with asians especially not just lena we have data with other gliptins as well including citizen showing that it has a higher efficacy in asian population when compared to caucasians especially whites and from the rcts that we know when you compare major dpp-4 inhibitors they all have comparable efficacy so about 0.8 to 0.9% hba1c reduction and

If you have a patient who have a higher hba1c to begin with you’re going to have a much pronounced effect like any other molecule that we know in diabetes practice right so this is just comparing all dpp-4 across and whether you use it as a mode of therapy or is a combination of sulfonylurea or even combining with t series if you are using t series in your practice

Which i do even if you compare it with combined of the t series you do have a good hba1c reduction tolerability there might be a subtle weight gain when you combine it with dz but it’s sort of not very much when you use only t-series alone so we have data with basil bowl is insulin and also you know data with sulfonylurea as well so overall it has a good efficacy

And this is all we know we know it has weight neutral we know dp before as a class has no risk of hypoglycemia very minimal risk of hypoglycemia right so what are the newer stuff that are coming out especially with what i talked started my presentation on is we have enough data with fatty liver especially in the animal model and also in humans which is going to

Be presented soon as it elevates the fatty liver you know we have seen improvement in enzymes we are safely using it in post transplant setting especially not immediately after transplant couple of weeks after transplant when we have to sort of reduce the bolus insulin dp before is something that we would start especially linagliptin because we have enough data as

Far as a fatty liver is concerned and what about elderly right so over 70 years i mean do i can i start it yes you have data not just with lena but all the other gliptins saying that it’s very very safe in elderly population because we know elderly population have a higher risk of falls and diabetes itself is a risk factor for osteoporosis a lot of women do or even

Men come to us with hip fractures with very subtle fragility fractures so it is important to prevent hypoglycemia and we have enough data with elderly population saying these drugs work well and we also have a cognitive study which is actually we will be soon published looking into the cognitive functions because cognitive disease in diabetes which is also called

As type 3 diabetes or alzhiemer’s itself is considered to be a type 3 diabetes because of brain insulin resistance we have data not just with lena but also with sit on other gliptins saying that it is it has or offers some cognitive benefits and about these are all very small studies which i sort of learned while i was preparing this talk we had the release trial

Here which showed it decreases ionic pressures in early stage of diabetes which probably could offer cardiovascular benefits if you actually start these agents early on in the treatment of diabetes and this is an effort study these are all very small studies we look at the number it’s only 16 you know 16 to 40 very small study is done for 3 to 6 months again this

Is only for 3 months but showed that it had better vascular protection in patients with diabetes by measuring the surrogate markers for vascular disease and this is again looking at that specifically at the vascular functions with linagliptin what it concluded was linagliptin tends to improve the endothelial and neurovascular micro vascular functions and it showed

A decrease in the interferon alpha and all the inflammatory markers which we think could be a cardiovascular risk factor in patients with type 2 diabetes so this is again a very nice study and a lot of times we don’t talk about it as a very small study use of linagliptin in the inpatient setting along with but a basal insulin so this is something we know we have

Been using in art practice as well even though the ata recommends all inpatient management should be done with insulin because insulin is the standard of care in the inpatient management but we have a very small study saying that patients can be on linagliptin with the basal insulin if they are non critically ill i will put it again non critically ill with mild

To moderate hyperglycemia in the hospital setting who are treated with oral medications at home because we know this doesn’t require any renal or liver clearance right so these are some of the newer studies that are out with the long rippln or all dpp-4 inhibitors same well the similarities are efficacy weight neutral hypoglycemia well tolerated and there are

Differences with cardiac safety heart failure and kidney dosing what we know with dp before especially linagliptin is there is no dose requirement adjustment required but other gliptins you have to adjust according to the renal function not because they are renal toxic but just because that those is enough for the efficacy of the glycemia control so that is one

Important take-home message it works across different patients with chronic kidney disease even in the setting of transplant we use it in renal and liver transplant setting as well and this is just the cv ot trials which dr. anand moses were already alluded to in the morning the carmelina was different because it also included the three and secondary endpoint it

Also included the composite kidney endpoint and these were the patients who were actually enrolled and carmelina trial and i’m going to just come to this because i have very limited time i have about a minute so this is just to show that dpp-4 inhibitors are very very very neutral as far as the cv safety so they are very that’s what fda wants it and it is a very

Cardiac safe medication as far as a heart failure dr. anand also said there is a black box burning for heart failure with these drugs that might change because with carmelina we had a non significant it was statistically nonsignificant but a 10% reduction in heart failure within our depth and so that labeling will change in the next year so there was no increased

Heart failure in any of these subgroups even in patients who had heart failure to begin with there were no increased risk for heart failure who were enrolled in the trial and there were also a long term renal protection which showed a reduction in urine albumin creatinine ratio which was also shown in a very smaller trial called marlene our trial which which was

New to me when i was preparing with three hundred and sixty odd patients showing that there’s a 20% reduction in an albumin creatinine ratio with dp before this is with all dpp force but this trial was specifically done with linagliptin so this is my last slide ladies and gentlemen so it might be used for a broad range of type-2 diabetic patients it’s one dose once

Daily after food independent of kidney functions liver functions cardiovascular safety including heart failure that we dwelled in the morning age i showed you in of data with the safety as was the age is concerned and also cognitive benefits and elderly bm mine because it’s weight neutral background t type to that it could be sulfonylurea it could be t series it

Could be basal insulin could be anything the background type two diabetic therapy or sglt2 which krishna is going to be talking about or the disease duration because the patients who were included in the commoner trial had duration of eight to ten years of diabetes so you it’s better you start these drugs early but you see the benefits at any stage of diabetes as

Well and also with ethnicity we do see greater frequency in patients especially the asian patients so with this i thank dr. g vijay kumar for giving me this opportunity to present this afternoon so i think it’s something to do with the pharmacogenomics right so we have pharmacogenomics which we talked about in the last session this we do have i don’t know exactly

What the genome occurs even for metformin induce gastric disturbance we have a gene that is responsible for the specific nucleotide thing so probably asians have the susceptibility for these drugs to work better so that that would be my only explanation i don’t know if anybody else it’s any other thoughts about it it’s krishna wants to answer that question 777th

Hypothesis basically well first question one is what is of course the pharmacogenomics i’m not so sure because look at the asian population which has both chinese and only 87435 or three bottles for tpp for standard standard one is fetuses dysfunction the greater the peter says this function the creative the benefit so you find the greatest benefit the ceiling in

East asians where the v dissenters commitments vary by as opposed to the caucasian is where insulin resistance is predominant chicken in the mit there seems to be an inflection point of bmi at which if you’ll be forced both better that she was inhibitors work better at a bmi of greater than 30 people pose better than mike nelson 30 this is very dirty nasty tired

In fact two of the indian tribes that took the typically force and there is an input actually show the greater benefits in respect and care and guess what is very common and both these operational fish similarly in korea but a bunch of other things but these sort of seems to stand out as one of the reasons why asian to work much better and interestingly we are going

To see some of this data from thank you the spot and that that’s a very interesting point and and it’s actually this possibility be true there are two kinds of people people always remembering down and the other so they will go i think that seems we’re 11 different in the level of actions of sorry will be p before which makes a whole bunch of thing but interesting

We remember that all of us before in a bit of the glp-1 action i would be well as shown that less than 50% of the people for any better action is made mediated through gfp one so 10 years of these molecules we are learning a lot of things thank you thank you thank you vijay and organizers for giving me this opportunity and i should appreciate greatness of this

Conference people are staying inside without a break they are not going out and it’s very interesting give them a big hand please and an audience we should appreciate them also

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Choice of DPP IV i – Evidence to date – Dr Shruthi Chandrasekar By Diabetes Dialogues Discussions 3D Conference