HALL C – CONFERENCE
Next i’ll invite dr sivatajo who is no need any introduction because he is the among the one of the or our organizing team of endocrinologists without wasting time i invite dr ratajara to start here thank you dr so thanks to all of you for coming here and connecting it’s it’s a great pleasure to see you all again physically so i will be talking over the next 15
Minutes or so about a molecule which have started using recently so that is a molecule called evocleptan and uh so it’s we all know it’s like a dpp for inhibitor so it’s a and it’s a selective potent and reversible inhibitor of dpp4 so whenever a new molecule comes in we we are slightly apprehensive how much studies are there to back its usage what is the scientific
Evidence behind all that so it it originally was approved in korea in 2015 and after that in multiple other countries and in india it was approved by the dg dcgi in august 2018 the dose is around 505 mg once daily so we know that there are some differences between the dpp4 inhibitors so the principal side and that difference relates to the site of action in the
Dpv4 enzyme so there are five s2 and s1 are the main targets of all dpv4 inhibitors and there are other subsites like s2 extensive s1 dash is s1 prime and s2 prime so binding to additional sites can provide additional dpp for innovation and increase the effectivity of the molecule and these are the classes broadly two broad classes of dpv4 inhibitors are there
Depending on their site of binding one is class one which binds to s1 and s2 and buildup lipton and saxoglyptic uh belong to that group the other group is s uh class two where uh where the molecule the dpv4 inhibitor binds to s1 s2 s1 prime and s2 prime and linagliptin and allogliptin belong to those who and evogliptin also binds to s1 s2 and s2 extensive binding
Sites with non-covalent bonding and the pharmacokinetics it it it reaches a peak at 33 to 5.5 hours dpp for innovation rapidly surpasses 80 percent in less than one hour and the terminal half-life is 32.5 to 39.8 hours so it it does not have any induction by any other enzymes it’s not an enzyme inhibitor and no those adjustment is required because primarily
The excretion is it’s it’s an urinary expression and those as an administration is in even in moderate hepatic impairment that we’ll see from the studies it does not require any alteration so it maintains a more than 80 percent dpv for innovation even after 24 hours the glp one postpandel levels are uh go up by almost 1.5 to 2.4 four times and the postprandial
Glucose level that goes down by 20 to 35 percent so there are multiple studies so there are phase three international studies which which initially led to the uh introduction of the molecule then there are efficacy in safety of evocliptin and treatment of type 2 diabetes mellitus in brazilian population the bridging study it was a randomized control trial one
Daily treatment of evocliptin 5mg you can see the hboc almost came down by 1.3 so there is the with 10 mg it came down by 1.33 with 2.5 mg it came down by 1.08 so it was more of it those findings study and 5mg was the usual dose that is approved and that is used all over so again there are evergreen studies presented in 18 2019 where evocliptin was compared to
Linux leptin there was no major difference in hb1c similar non-significant difference in hbnc reduction about 12 weeks there is no difference in glycemic variability as well that is a concept which has which is rapidly evolving and even if the speech if this patients were further followed up till 24 weeks there was no change in advances so effectively we know
That linagliptin is a very standard molecule which has been very extensively studied and it it does reasonably well in comparison to linagliptin even in randomized control trials so those these are reassuring findings in terms of their safety and efficacy for for patients with type 2 diabetes so a very common question again that comes to our mind is whether we
Can use them in chronic kidney disease patients because glypton as we all know has emerged as a very safe way to treat type 2 diabetes and ckd so because they do not have the risk of hypoglycemia they are they can be used in modes most stages of chronic kidney disease and there was a clear this study was specifically meant for patients with chronic kidney disease
And all patients all stages of ckd but except those who were on hemodialysis so they have not been studied so secret is stage one secretive stage two second stage three security stage four that is even if the gfr is uh till 15 you can safely use evogliptin without alteration in in the dosage so it’s as similar to linacleft in terms of that but for in-stage kidney
Disease patient who are on hemodialysis we do not have adequate data again another area which is a very common complication of type 2 diabetes even type 1 diabetes also sometimes is nafld so there are uh there are two aspects to it so whether using a glyph there are some studies which suggest that leptin can be beneficial to uh to maybe the liver fibrosis goes
Or the liver fat fat content and whether you can use safely in the setting of electronic liver disease so there are initial small studies which suggest that they can be slightly beneficial in chronic liver disease and there are trials which suggest that if they can be safely used for childbirth stage 1 stage 2 for stage a and b we do not have adequate data for
Child proxy so in those group of patients it should be avoided but in initial a stage and stage b cld you can safely use it so another area which which has generated a lot of attention is cardiovascular safety so we do not have a dedicated cardiovascular outcome trial for evogliptin as of now but we have a nationwide population based course study in south korea it
Was more of an exploratory objective and the the the clinical and demographic characters of patients with type 2 diabetes on glamipide dpp for inhibitors and hdl2 inhibitors were compared so it was more of a observational registry based study and the study concluded that the use of evocliptin either decrease the risk of cbd or had no association with cbd compared
To other ingredients of dp4 inhibitors or hgl2 inhibitors so it’s as safe as other tpp for inhibitors or hdl2 inhibitor and even there are some suggestions that there are a trend that if if you are comparing chlamydia to dp before any two evocleptin actually it did better in in comparison to glimmi pyrite though in an observational setting uh in terms of cv outcome
So we now look into some of the combination studies we studied the combination of evogliptin and metformin so they these group almost close to a thousand patients were studied in different randomized control trials there also they showed adequate safety adequate adjuvancy reduction even there are indian studies multinational global studies so this is a molecule as
You can all see has been quite extensively studied in korea in indian setting in other countries also and it has done well in comparison to linagliptin even it has been compared to cetacliptin it’s it’s cv safe it can be used in stage childhood a and b chronic liver disease in you can use it in most stages of ckd unless the patient is on hemodialysis and there are
No additional adverse effects as compared to other tpp 4 inhibitors so in terms of total adverse effects or pancreatitis they’re as as good or as safe as the other tpp before inhibitors so we we again hypoglycemia risk so if the person is not on uh sulfonylurea or insulin you you will not be the person again the risk of hypoglycemia is practically nil and we have
The latest data from india also for a retrospective observational study of usage of hypoglypton in type 2 diabetes patient so that also suggested that it was quite safe the results were mostly decrease was almost more than 1.2 percent so multiple events cgm data suggests that they do quite well so effect of evocliptin on addition there are studies where it has
Been added studied after metformin and limited combination again good encouraging data eight point eight was the baseline age once it came down to seven point eight and it uh if the fasting blood sugar came down from 159 to 128 the post pentel came down from 238 to 188 and we there is the active post marketing surveillance of the fixed combination of evoclifting
And metformin going on and so it’s a thousand film coated by layer tablet and so the change in hb1c is comparable to if you even if you are giving it differently so overall as you can see it’s a safe molecule it’s comparable to all other leptins in terms of safety efficacy expense reduction usage in chronic liver disease usage in chronic kidney disease no major
Enzyme interactions no enzyme induction no issues related to enzyme no no other enzyme inhibitory effects so overall it’s it’s a quite quite safe molecule and the age once reduction in most of the trials has been in the range of 0.7 to 0.8 if the h1 was very high at baseline even it has come down by 1.2 or one point four percent so this was a meta-analysis of usage
Of evocliptin which was published by deep i was also fortunate to be part of this meta-analysis so there also we found that it when it was compared to other glyptons so it it it’s almost similar to most of the other glyptons so it’s equally safe equally efficacious even we have meta-analysis which is published in indian journal of endocrinology and metabolism to
Suggest that so to finally to summarize today’s presentation on evocliptin it’s a true or truly once daily uh dpv4 inhibitor so you can you need to just give it only once long half life of 32.5 to 39.8 hours it has data to support its cv safety renal safety hepatic safety there is no need to change dosage in various stages of ckd the in the evergreen study which
Is a 24 week study which was called where evogliptin was compared to linagliptin it showed the highest reduction in glycemic variability sometimes it did better than in in terms lenovo reducing glycemic variability and they were as well as so and was non-indian non-inferior to statistically to linagliptin in terms of h1z reduction with three head-to-head studies
Against cetagliptin evogliptin also has been proven to be non-inferior versus acetoglyptin and we have a indian study of called evolution india also which suggests that it it is as safe as cetagleptan so evogliptin metformin release combination so sometimes what we see in clinical practice is that most of the dpv4 metformin combinations they have an immediate
Release preparation of metformin along with the tpv4 so sometimes patients do have issues related to gi side effects and gi tolerability but the metformin in this combination is a system release metformin so sometimes if the patient who who is not able to tolerate the immediate release metformin shift with sustainable formulation the gi side effect somehow
Actually settles down in many of our patients so even in the metformin in the evolution metformin combination is a sustain release so that is actually helpful for patients who have gi side effects related to metformin and can and it can be considered as a once daily dosage for many of these patients so if we have a comparison to other type of inhibitors the it
Is the percentage of tv for innovation is almost similar it’s like 80 so it varies between 92 percent to 90 to 80 percent for the seven for most of the dpv4 so it’s overall tp4 innovation is 80 selectivity is high dosing it’s one’s daily dosage those alteration in renal disease is not required those alteration in hepatic disease so you can give without any dose
Alteration in childhood b a and lowering versus active comparator so it’s very similar results qt prolongation it does not cause so there are some issues with uh ternary leptin in terms of uh qt prolongation so this is not their risk of hospitalization for heart failure so even though we have a we don’t have an uh dedicated cv outcome trial but whatever initial
Data we have there is no risk of hospitalization for heart failure and available in indian setting cost always remain a important deciding factor about which drug to prescribe and this is not not a molecule which is very costly so it’s not as costly as the conventional glyptons we have in market this is a new molecule with adequate safety data which you can you
Can consider in many of your type 2 diabetic patient thank you for your patient listening so i will hand over the session now back to the therapist thank you so regarding your excellent presentation about this new molecule ever lifting so if anybody has any questions is quite long 32 to 39 hours what about the complete effect after say week those are after 10
Days some amount of drug must be there in the blood already so that will be at the end of 24 hours if how much dpp for innovative activity is present so that that is almost so that remains static so even though some of these drugs do have extended half-life they do not have any uh cumulative effect as such thank you dr sabrishi for this nice presentation have
A question that among all kleptins where do we place this glypton for cardiac patients we do not have a dedicated cv outcome study with this yeah yeah i i think i wish we had so obviously if you look into hard evidence so if what you have for maybe cetagleptin or linagliptin we do not have that for evolution do we have some data related from a registry which is
Korea based but if somebody is having a genuine cardiovascular disease you have data from selenium leptin or units cetagenesis as that it does not increase the risk of heart failure so but we do not have such data from evocliptin so maybe your approach should be slightly guarded so you can even do we see very often patients getting glypton which which does not
Have any cv outcome rally when we do not have cv outcome trial for builder glypton so if you are looking at really safe cv outcomes really robust cv outcome data suggesting cv safety in in patients who are having some amount of cardiac compromise so we only have cytoglyptin and linoglepton as molecules if you are looking into hard evidence so otherwise you can
Extrapolate thank you thank you thank you thank you
Transcribed from video
SPEEDCON 2022 – 5th ANNUAL CONFERENCE By SPEEDCON
