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Cutting Edge: Episode 18

Mar 04 | 3:30 PM

Watch Dr. Mahadev Desai discuss on 'Uncombable Hair Syndrome' (UHS) is a rare disorder of the hair shaft of the scalp caused by mutations in the genes, having no definite treatment, usually resolves or reduces on its own in adolescence. Dr. Rakesh Sahay gives his take on different aspects of semaglutide: first oral GLP-1 R agonist available in India, in Phase-3 Pioneer trial it shows superiority above other all agents with no risk of hypoglycemia, no weight-gain and is non-invasive method.

[Music] good evening everyone uh we are glad you could join us today uh this is 18th episode of very amazing show on matrix cutting edge uh and uh this is uh on this eighth we have uh experts joining in uh so before uh so uh this show is actually hosted by dr mahadeva who is senior consultant physician uh from the back uh good evening we begin your story number seven with a picture of a boy and this has made the noun in the many social media instagram many other platforms i'm sure you must also getting somebody's almost similar pictures right in your social media accounts right so why we have picked up this story even though it is claimed to be very rare this 100 as a child that story is coming up every few days and then every child is added is only one in the hundred so but basically we'll go ahead and see this is a story of an uncomfortable hair syndrome uncombable hair syndrome ah as as i said earlier this particular picture there was with the caption that my child is 100 confirmed cases of uncomfortable hair syndrome it's a rare disorder of the hair soft because of the mutations the three genes which are proteins which are used for the development of the hair shaft it affects only the hairs hair's scalp and its hairs of the scalp and no other parts of the body and it may become apparent within the three months to up to the age of 12 years usually it is characterized by silvery blonde or straw colored hair which grows in disorderly fashion it can grow in any directions and that is the reason it doesn't it's not easy to calm that hair flatly and why we have picked up this story that though it is considered rare but as i said one of the boy that was shown in the picture has claimed to have only 100 but when we dug into the history on the google search we could find that one of the boy the girl was diagnosed to have this uncomfortable hair syndrome the very scientists who diagnosed in 2018 she said dr beth regina betsy said that she had diagnosed 70 cases already in 2018 and sees of the opinion that there are at least 1000 such uh patients born with a combiable hair syndrome and basically the quantity of the hair remains normal there is no definite treatment and most of the sufferers they either resolve or reduces on its own in the adolescence and that could be one of the reasons that the number of cases are not reported and we don't know the exact numbers and what is important is just give a gentle hair care using the very small hair conditioners or the soft dresses avoid the harsh brushes or the certain specific treatments like pumps or chemical reactions or excessive brushing or blow drying in fact the very appearance of the unruly hairs or the curly hairs wright gave one of the sufferers mother that very name they gave to the their post as einstein too but in fact most of the adults they outgrew the disease and by the time they come beyond adolescence they do not have this problem so probably of course albert einstein was not investigated but surely he did not have uncomfortable hair syndrome we move on to the next story that is about the novel biomarker for pulmonary artery hypertension in copd we know chronic obstructive pulmonary disease is one of the third leading cause of death in 2019 statistics and chronic obstructive pulmonary disease the main important etiology is the topical related injuries and it leads to pulmonary hypertension and that increases the mortality manifold the conventional diagnostic methods for pulmonary hypertension if you want a definite diagnosis it is a right heart catheterization and to know the exact pressure of the pulmonary artery but we can of course diagnose with the two dimensional like with the doppler as one of the investigative tool and what is known is the because of the injury of the tobacco to the endothelial linings there is an deranged angiogenic signaling and inflammations it also produce inflammations and there is new engine new vessels formations and that contributes to the pathogenesis of pulmonary hypertension and it leads to the altered circulating angiogenic factors as well as the cytokines up till now we have no circulating biomarkers or the blood indices to diagnose pulmonary hypertension here in this particular study the researchers they first have a screening cohort that means they first tried to prove the concept right by way of selecting four patients having a chronic obstacle bone disease with pulmonary hypertension the copd diagnosed by the global criteria and the pulmonary artery systolic pressure was more than 35 meters by the 2d core doppler studies so four patients having the copd and pulmonary hypertension and four patients having copd but not having permanent hypertensions then once they approved the concept they went to the validation cohort wherein they selected 46 copd patients out of which 28 had pulmonary hypertension and 18 patients of copd did not have pulmonary hypertensions and what they did they analyzed the their blood for the presence of whether there is any human angiogenesis of proteins or human cytokine proteins all these kids are available wherein you can have as many as 55 in angiogenesis markers and 36 cytokine markers what they found was that out of this 55 and 36 total proteins there is only one protein which is called tissue inhibitor of metalloproteinase one or ti pm timp1 which was correlated with the diagnosis of pulmonary artery hypertension in copd so then they went on further and they what they did they just selected a particular brand of cigarette they extracted the tobacco from it and then they created this cigarette smoking extract and they mix up with the human pulmonary artery smooth cell muscles which are available in the laboratories and they also picked up this small muscle cell medium smooth muscle cell mediums so they put the blood with in the cigarette smoking extracts and they analyze the levels of timp-1 and what they found was that the timp levels was increased manifold in patients who have copd and pulmonary hypertension compared to the patients without copd without pulmonary hypertension so what was the conclusion was that now we have got probably one blood marker or a biological markers which may be able to we may be able to diagnose pulmonary hypertension well before it becomes very severe and the levels of ti mp1 were correlated with the degree of the permanent hypertension and severity of the copd so maybe in future that becomes one of the routine tests as now we do many blood markers biomarkers for the other disease like we use vnp for the consistent heart failure or we use proponent for the marker in functions maybe this one marker may be useful in the diagnosis of copd with pulmonary hypertension then we move over to another story the story is about whether nostalgia relieves the chronic pain this appeared in the journal of neuroscience on 20th of february we know it's a very common experience the day we are very tired exhausted or having a headache and body ache and suddenly we get some good news or we get the call from a buddies right and suddenly everything changes we become more energetic all our pains disappear and that's exactly what is a common experience with most of us so the chinese academy of science also wanted to know whether this kind of nostalgic images help us in changing the perception of the pain so what they did they selected two groups of persons volunteers right in one they sold the nostalgic images of the childhood like a popular candy or a cartoon tv show or a school game or their family pictures of the childhood and another group they just keep the conventional pictures the modern day pictures right and what they did was they measured the brain activity of the adults with a functional mri they did the functional mri and they see what is the activity of the different parts of the brain and at the both in both the groups the one group was the one where the nostalgic images were shown the other was the one where conventional images were shown some images have to be shown to correlate which part of the brain is activated and for pain they use the thermal stimuli so they give thermal stimuli and they saw which part of the brain are activated during that period and what is the peace and the volunteers rating of their pain threshold so they could see that over the thalamus was definitely one of the center which is a relay center we know thalamus is this the center for the highest perception of the peripheral pain but also it has to correlate with the higher centers like the para hippocampal gyrus and the lingual gyrus so the activity was shown in both these areas also when the nostalgic images were sown which was not there in the conventional images so they could say that the tel we know that thalamus is involved in the relaying of the informations between the body and the cortex and it was correlated with both nostralogy and pain ratings nostalgic emails reduce the pain ratings the group which have shown the nostalgic images and the same pain threshold in the form of thermal stimulation had a less pain that is reported than the conventional group and they could see that the the nostalgic image is also reduced the activity in the left environmental gyrus and lingual gyrus as well as the para hippo campus which are the areas which are implicated in pain perceptions so the conclusion was that maybe for chronic mild pains it is better that we involve the nostalgic images or for our own we can say that when you are extremely having this kind of eggs maybe we start thinking of something uh of previous years as a nostalgia maybe we see the albums or our childhood film pictures and then that itself might reduce the pain then we move on to the story number four which is about the use of artificial intelligence for reducing the antimicrobial resistance and how to prescribe antimicrobial resistance using this artificial intelligence right so what they did that this was a study which is a collaboration of the israel institute of technology biology and computer science and what they did they collected the data of eight years of records of more than two hundred thousand patients for their microbial profiles their previous culture reports the sensitivity about their histories and then they focused on two common infections one was the urethrac infection another was the wound infections and they also tried to correlate the whole genome sequences of over 1000 samples which are pre and post treatment bacterial isolates and they put it into the machine learning analysis of another on one leg 40 000 unitec infections and over 7000 bone infections and they could see that if they can train the machine by putting all this data including the past histories and the previous report sensitivity reports then they could come out with an algorithm which will give on the next time when the patient have the infections either utron infractions they will come out with a particular antibiotic and that was matched with the antibiotic which was prescribed by the physicians and they could see that the antibiotic which was suggested by the artificial intelligence had a more chances of the sensitive infections compared to the one which was prescribed by the physicians and the reason was that they could find out from the analysis of the previous eight occurs record was that most of them these infections occur from the patient's own microbiota we know that there are so many organisms which are the common cells or lying over our skin or what the in nearby the wounds so what they could see that really it is the same infections either which is incompletely treated or had developed resistance and if we have the history of past history of the sensitivity reports or the number of drugs that is used maybe we come out with the correct prescription of antibiotics which will reduce the resistance and which cut down the course of the antibiotics so that is all about our first four stories so we are discussing the particular review article which appeared on yesterday's english journal of medicine that is about chronic pancreatitis we know chronic pancreatitis is a progressive fibro inflammatory disease and the classical chronic pancreas is usually associated with either alcohol use or smoking or certain genetic mutations and typically it begins with the recurrent bouts of pancreatitis followed by insidious development of chronic abdominal stability pain next in the next three to five years after the initial onset and it is end up with the exocrine pancreatic insufficiency or endocrine pancreatic insufficiency in the form of statoria weight loss sarcopenia and many of the deficiencies of soluble vitamins that is aden k and the particular review article suggests that there are three types of chronic pain classic pancreatitis type a b and c type a is one where there is intermittent severe abdominal pain attacks with or without pancreatitis which occurs usually in the early part of the disease while type b is a persistent chronic pain between the intermittent severe attacks and type c that is what we normally see over a long period of time is the chronic severe pain without severe attacks and the chronic pancreatitis leads to many complications on the long run that is pseudocyst biliary structures exocrine and endocrine insufficiency bone loss and it's also one of the predisposing factors no matter it's a type a b or c it is one of the important risk factor for pancreatic cancers the investigations we know the classical findings of chronic pancreatitis is a triad of pancreatic duct dilatations calcifications and the atrophy of the parenchymal parenchyme of the pancreas city abdomen obviously is one of the best investigations and easily available at most of the places mri is as good but ct is can be less expensive and ercp definitely gives a pathology a direct visualization but it has its own complications cost and expensive one the very important test which has been mentioned in this particular review is about the estimation of fecal elastase level we know that pancreatic elastic is one of very specific pancreatic enzyme which is released and if it is in a lesser quantity in the stool say less than 50 microgram per gram of stool there is a definite definite diagnosis of statoria higher quantity may be seen in many other diseases like diabetes and and the fecal fat is which we have been conventionally doing it that patient is subjected to consume the 100 grams of fat for two consecutive days and then for next two days during that also patient has to consume high fat and the estimation of fat content of more than seven gram in a day stool is indicative of fat mole digestion the management or that is mentioned in this particular review is about the for the pain as well as for the duct structures so for pain the most important it mean remains the analysis six and most of the patients if not taken care would be hooked to the narcotic analgesics antioxidants have a very limited role and the most important treatment to take care of this tutorial is the pancreatic enzymes here would like to have our experts opinion about the dose that we should be giving it's mentioned that most of the time that is an under dosage and that doesn't give the enough of the response to the statoria that the international treatment can be in the form of removal of the stone by arcp or if there is a smaller stone less than five millimeter we can go for the lithotrapsy and surgical treatment obviously is in the form of ductal drainage or resection of the procedure so this is what is mentioned in the review article but we want our expert doctor ahmed to give his opinion about the in the real life how they manage with the chronic pancreatitis patients how often this economy can catch patients and how they investigate as well as manage so over to you sir yes sir thank you actually it's a very good article actually it gives and capsule as to how we need to deal with a chronic pancreatitis although many of the patients may come with history of fracking francotities in the past sometimes actually they won't have much of a history and when you go into detail past history they might just give a history of dyspeptic symptoms but when they present to us it'll i mean they'll be a full bone for chronic calcititis and it they will be having a diabetes mellitus because of the exocrine insufficiency i mean endocrine insufficiency and they'll have stereotoria because of the exocrine insufficiency and it's very difficult actually to control the sugars also it's because it's highly erratic because when we give the insulin the counter regulatory hormones are also affected so actually they i mean it's very erratic sometimes they'll go off i mean the sugars will be very high you give insurance they'll go suddenly to hypo glycemia so it's very difficult to control their sugars i think the entrepreneurs will be able to say much regarding that so regarding the evaluation wise yes actually when we see a patient with chronic calcific pancreatitis we first thing is we do image yes ct is the best cet will show actually much more than the advantage of the mri is radiation is less and even in patients with chronic kidney disease we can do we can get t2 weighted images so that the contrast actually is not required we can get a clear image of the ductal system but whereas calcification sometimes can be missed in mri where a ct we can it's just like an x-ray we can clearly pick up the calcifications and then yes actually when here when when a patient presents to us and if the patient gives a history of stentoria it's not always necessary that we need to send for elastase or fat actually what we sometimes we do is we give a trial of the enzymes and we look how the patient improves and that itself is actually a diagnostic that the patient has got exocrine insufficiency so you need not always test for stool elastase stool elastase the problem is like sir said ideally although the labs say less than 200 is suggestive actually because of that we get a lot of false positive cases so ideally it should be less than 100 but less than 50 yes definitely there is exocrine insufficiency and fat estimation we hardly do then another thing is we opt is we do eus endoscopic ultrasound actually sometimes actually the subtle like sir said this is actually a lesion because if you look at that they have an increase over you as each 10 years go by their their tendency to return malignant is 1.4 times then it becomes eight times each ten years as we go forward so we do screen our patients with ultrasounds and endoscopic ultrasound because if lesions less than two centimeters sometimes the ct can miss so endoscopic ultrasound is more specific there and the ductal system also we can make out better with endoscopic ultrasound the best will be m mrcp that is secretin-based mrcp where secretions come we can clearly delineate the buckle system both the biliary as well as the pancreatic and um yes yeah so anything is see some of the patients we don't have when you take the history measures give them won't be smokers won't be alcoholics but then they do get they do get the chronic acid pancreatitis well we say that it's genetic sometimes we do test it's very expensive but then even if we find out manage advice it does not make much of a difference only thing is probably we can say that some of them are genetically i mean if you take the prss one ling gene related uh pancreatic and it is autism dominant so we can say that you know you have to look for your family members probably that is only a positive thing that we get out of it we can screen them other than that the managing advice doesn't make much of a difference coming to the man management wise yes pain is actually it's very difficult to control especially when the patient has got severe atrophic disease it's very difficult we try having various groups of painkillers then you can try gabapentoids tricyclic anterior presence and ssris we do try and in some of them if you are not able to get relieved we do them in surgery surgery is another option that is basically we decompress them see the pain is basically due to increase in the toxic pressure okay so if we if there is a structure dormant structure that is towards the head region or the body region or if it is a calculus producing obstruction producing increase in the ductile pressure like sir said we can do if it is a stone less than five centimeter five mm we can do um lithotripsy and that might take care of it and if there is a structure what we do is we try to uh we dilate the stretch and put stents actually plastic extends across and we see really nice increase the size so that we can actually dilate it so that you know so any chronic pancreatitis patient with resurrected abdominal pain if there is a dilated ductal system actually standing might help in reducing the pain attacks and yes taking care of the calcifications are the ductal calcifications if we are able to break down and bring it out yes definitely that will help and if whatever we do endoscopic therapy medication we are not able to help then probably will have to go with surgery that is we have to decompress the system the procedures like the phrase procedure where they do a lateral pancreaticogenostomy where the duct i mean the system is connected to the duct so that it will decompress into the system and yes malignancy is always a worry for us in these patients and then yeah definitely regarding the um firt that is a pancreatic enzyme replacement therapy we always give suboptimal doses i hatch actually actually it should be 90 000 industrial units minimum should be given and our formulations are like five thousand ten thousand twenty five thousand it's very expensive we can't uh blame them for not taking it measure of the patients actually stop it because they are not able to uh buy it actually otherwise ideally what they should at least 30 000 units with each meal along with the first bout of meal uh should be taken so that and what we advise is if at all we usually advise to decrease the oily content in the food but then that is counterproductive because sometimes the patient will become they'll lose all the fat and muscle so we actually ask them to take normal uh fat diet and if and we always advise them to take an extra tablet if they think that they have taken an extra fat email okay yeah and regarding the malignancy yes it is very difficult and one of the few pointers which say that you know the patient may have underlying malignancies they'll have on sudden uncontrolled diabetes because ccp can produce diabetes a sudden uncontrolled diabetes i mean usually which was under control suddenly becomes uncontrolled then yes definitely it's a red flag sign then sudden loss in weight again is a red light sign persistent abdominal pain is again a little red flag sign so these are some of the red flag signs which say that okay maybe he's having an underlying malignancy so what we do is we usually screen our patients every six three to six months with ultrasounds and at least one to two years within one to two weeks we do an eos or a cd so that you you don't miss and we do send a say cn99 levels which is the only marker but just because it is normal does not mean that the malignancy is not there it can be even be elevated and cholangitis sometimes ccp solutions may have a benign biliary structures uh which can produce mild colonization but then that is that is only marker that we have so we always send it and see whether there is a rising trend or whether it is very high or not so these are some of the ways i covered everything absolutely covered very everything and simplify and as you rightly said that we have endocrinologists so we'll request dr shahai to show through some light about the management of diabetes and chronic and creatities does it differ from the conventional manager of type 2 diabetes dr sahai is the professor of medicine at the endocrinology at the osmani medical college hyderabad welcome sir it's our pleasure to have you here yes yes sir thank you for inviting me to be here on this platform uh it's a pleasure being here and as uh was highlighted just now that uh i think the diabetes management is pretty much a challenge in patients with chronic pancreatitis because of the fact that they have a significant insulin deficiency and they don't have much of endogenous insulin although they don't go into ketosis one of the characteristic features is they don't go into ketosis unlike type 1 diabetes who also have a white fluctuation their glucose levels have a higher insulin requirement but these people also have a similar sort of situation but they don't go into ketosis that's the only difference but but they are they need always need insulin they cannot be managed with the oral anti-diabetic medications and uh and and one of the few things that we should keep in mind today is that you know the dpp for animators have become very commonly used medications so we have to be careful with the use of these medications in patients with chronic factories because that's that's one one area that we should keep in mind because otherwise are sort of very good agents which can be used in a i mean without thinking much you can use them in most of our patients with type 2 diabetes but this is one scenario where you have to keep in mind that you should avoid using vp or gf1 analogues for that matter and i think that's that's one [Music] [Music] one other aspect that is just mentioning is that we are seeing people with type 2 diabetes also having significant uh pancreatic enzyme deficiency uh exocrine insufficiency so that's again a emerging area of research where thank you very much sir for your inputs and we want you for our next story that is coming down the line and thank you dr ahmed ahmad for your presence and we wish that you also stay for the next two stories i'm actually preparing for this absolutely fine it's a real thank you sir thank you for this thank you yes and then we move to the story number two that is about the novel dressing technique to prevent surgical site infections we know that whenever the for surgeon it's a nightmare to have a surgical site infections because it becomes very difficult to manage and the very purpose of the surgery is defeated so every year almost around 300 000 cases of the surgical site infections are reported within 30 days of the procedures and resulting to as many as 13 000 deaths so and it's also proven that the bioactive vitamin d the active form of vitamin d is definitely helps in body's production of the endogenous antimicrobial peptide which is called the ll-37 ll-37 is a particular protein which is linked to a gene that is called camp gene or catholicidine antimicrobial peptide which is present in our body and which produces the innate immunity and which resist the nature the infections and that is why we don't get infections every now and then in spite of whether we have received prophylactic antibiotic or not so what is done by this oregon university researchers is that they develop a particular protein called vid 400 which is a natural enzyme emitter for the cip2 cip2424a1 and that is incorporated into a nano based bone dressing and then also they have added active form vitamin d and with the idea that this all three will put will produce the endogenous antimicrobial peptide ll-37 and which will increase the immunity so that there won't be infections and since it is a natural product and which is not an antibiotic so only we will have less chance of getting the drug resistant to the antibiotics that we give or really we may not need to give the antibiotics and what they did was they they found out the transgenic mice and they used the dermal wounds over the transgenic minds and all use applied this dressing and then they also repeated this experiment on the human skin tissues which is there are from the plastic surgery patients and they use this and they could see that the infections are less and so that is all about the new dressing and hopefully we will get this available soon so that our all surgical colleagues will be happy and maybe we have to use less and less pre-exposure prophylaxis for the surgeries and then we move on to the our very top story and that is about the first oral glp one receptor agonist available in india called sema glutathione and for this we have professor rakesh shahi who is the professor of endocrinology at the osman university we already heard him for the earlier story sir we welcome you and we would like to have your inputs about this new molecule which has definitely a game changer for the management of diabetes this very article is written by our very own indian scientists starting from dr anuk misrasar who is the chairman of the 40th hospital and also the awardee of the bc raw award as well as the kazmastery award dr aldisin and dr ritu singh both are the calcutta the specialist and they have published this article and we know that when it comes to glp1 receptagonist until now all the drugs which are available were all the injectable ones hexanetide was the first which was made available in 2005 which was the short acting one thereafter came the long acting resonating then lexi sanatide lyra glutate albiglutite doula glutite and the last one is the semaphotide and they are very useful drugs because they correct many pathological mechanisms of the diabetes they increase the glucagon level they reduce the hepatic glucose output they increase the glucose dependent insulin secretions so that and they increase the gastric emptying time so they also produce weight loss so many diabetes related pathologic mechanisms are attended by this particular group of drugs and that is why definitely it is one of the most welcome molecule the major drawbacks up to now were the injectable compounds very expensive and the gastrointestinal intolerance the as i said this trial of doctor nook misra doctor kumar singh and ritu singh have done an exhaustive search from the pubmed and the google scholars from inception till 31st january 2022 and they could get all the data this print all the data from all the studies where this hemoglobin was used and they could come out with more data of more than 9500 participants in 10 randomized tracible control many were the rcts and we know that all these studies were the pioneer studies and in which the oral sema glutathione was used and this particular studies had included were included in the meta-analysis and obviously the patients were pancreatitis or proliferative retinopathy maculopathy or neoplasm in the first previous fires were excluded from these pioneer studies and what the outcome from the dr singh and i'll have found out that the oral semichlorotides 14 milligram is superior to placebo as well as active comparators the pioneer studies are many they include different types of the oral anti-diabetic drugs like the empire glyphosene or cetagliptin metformin and they could show that the 14 milligram of oral semigluted is superior to in reducing the hp1c always as well as in the weight loss and it doesn't require any change in the dosages if the patient had comorbid renal or hepatic problems regardless of the degree of dysfunctions we can continue with the same dose and the gastrostyle intestinal side effects are definitely there and some major concern but what they could find out from the one of the pioneer studies what that if we can escalate those gradually start with the three milligram for one month and then gradually go to seven milligram and then fourteen milligram probably the gi tolerance is better and the one of the pioneer studies also showed that it is non-inferior to placebo in the cardiovascular outcome the unfortunately in all these foreign studies the relative representations of the indian patients were few so we may not extrapolate these results into our patients so for that this is why we have doctor professor rakesh shahi dr singh was also supposed to be here but really he was busy with some enterprise meeting sir we welcome you and we need your expert opinion about the real world data from the india as well as there are many things about oral sima glutathione we'll be using it if the cost is not an hindrance so we need your expert opinion about different aspects of the oral semicrotide thank you thank you once again for inviting me to be here today i think you have picked up a very very useful and relevant article because this has been a game changer now actually you could call it as a game changer because it's made a big difference in terms of you know management of diabetes because uh glp one analogues as you as you have rightly shown there tackle eight of the uh six or eight defects as you say indominus object we say that you know we have ominous operate when you're dealing with diabetes the eight different mechanisms which can contribute to hyperglycemia although there are many minor mechanisms still there but eight major mechanisms by which hyperglycemia develops in patients with diabetes so if you look at the glp one analog there they are actually addressing six out of these eight so that makes it very useful and uh and it has been shown in this clinical trials as you've shown that in the phase three clinical trials of pioneer you have seen that it is it is much uh more superior with uh dpp foreign emitters you find that there is a clear superiority of this molecule as compared to all these agents now as compared to insulin also it remains a better molecule because it causes it has a very low risk of hypoglycemia and does not cause weight gain these are the problems with with incident that all the insulin can bring down the hvac to it to a to any extent as you can say but uh the problems with insulin use are that all the insulin is also similar to glp1 analogues in terms of being a injectable therapy but it can cause hypoglycemia it can cause weight gain so those things don't happen with the glp so glp1 analogues are standing out as compared to incident also as preferred engines when you're looking at the oral agents but when you're looking at uh but when you're looking at uh injectable i mean when you're looking at the injectables the the problem of overcoming the problem of having injectable therapy then this oral agent comes out as it stands out as superior to that so now how was this developed was because they have this a peptide is added to that called the snack which increases the uh which in the gastric mucosa it increases the stomach ph avoids the degradation of the of the peptide molecule and allows its trans trans cellular absorption so although only one percent of the total dose is absorbed but it is a innovation it's a true innovation in in the sense that it has made a real change in terms of allowing peptides also to get absorbed in the stomach and so that is the the the innovation that is seen in this molecule and we have seen the proof of from all the studies now we're waiting for two two cardiovascular outcomes i mean one major cardiovascular outcome trial called this whole study which is ongoing and which we are likely to get results in a year or two which will show whether it is unlike all the other uh injectable glp1 analogues like diagram and also sigma glutathione whether this oral symmetry also has a cardiovascular benefit uh which is expected because it is working through the same mechanism and it has been shown uh in terms of all the other efficacy parameters it has shown to be a good molecule superior to all the other agents right we have rightly pointed outside that that particular semi glutamate is prescribed co-delivered with the fatty acids small fatty acids so that it's being a protein otherwise would get digested with the acid ph as well as the proteolytic enzymes in the stomach so but how do we take it there is also a specific way we have to consume the oral there is a glutathione that is another another challenge i mean in terms of when you're prescribing it you have to educate the patients about this the patient has to take this molecule early in the morning first thing in the morning on an empty stomach take it with just 120 even half a glass of water because too much of water will also cause the molecule to get washed down the stomach because we want it to be absorbed in the stomach so therefore a small quantity of water uh on an empty stomach it has to be taken after taking this molecule uh up taking this tablet the patient has to remain empty stomach for at least half an hour although one hour may make it better but at least half an hour of being empty stomach will ensure a good absorption of the molecule a better absorption than if it is if something is taken before that many of our patients are also taking thyroid medicine so can we give that together or we have to have so that is again challenging because thyroid medications also have a problem it comes in terms of the absorption but i think uh going by the by the requirement the very stringent requirement of this molecule it's best to take this molecule earlier and then after that you can take the peroxide because even if thyroxine absorption is affected to some extent because the of the earlier use of this molecule you still can increase the dose of thyroxine a little bit if required but you know this molecule is is more expensive and i think we need to focus on seeing that this gets gets absorbed effectively and patients get the maximum benefit from the use of this function right plus i think there is a notion that thyroid medicine has to be making in the morning in fact it has to be taken the empty stomach that is more important than taking only in the morning but for this particular molecule it has to be taken in the morning that is there is no doubt about it is that in many places uh in the world where uh they have an early supper i mean we tend to have a late dinner but uh people who have an early supper at about six o'clock or seven o'clock so they go to bed at about 10 o'clock 11 o'clock in the night and that's the best time to take the thyroxine because that uh becomes a very good uh time for taking that in our country because of our our eating habits and all that we prefer to take it in the morning but we could do that molecule and taking oral hydrate then i think the thyroxine can also be shifted to the night right sir another interesting question is there any difference in the oral as well as injectable cemu glutathione as far as the gastric side effects are concerned yeah as compared to the gastric side effects they are probably similar we could say they are not much different but what has been seen is that the oral molecule has slightly better tolerability as compared to the injectable preparations uh this is what is uh our personal experience also and uh and and also although there is no clear comparison on this aspect but whatever available information suggests that this is probably the oral tolerance i mean neural molecule has slightly less gi uh intolerance as compared to the injectable questions right so there is also a concept of cost to control analysis right when it comes to the such an expensive drug so what have you to say about this yeah so this is an expensive molecule actually if you look at the cost of the molecule itself it is very expensive but what you have to factor in is that what you have to look at the cardiovascular the long-term benefits that you get because we have got clear data showing that the use of these molecules has slows down the progression of the renal disease slows down the progression of the cardiovascular disease and i mean has this benefit in terms of providing protection against cardiovascular and renal disease so if you're looking at the cost of managing cardiovascular disease or managing renal disease so if you factor in that cost then definitely the cost that you're going to pay today becomes much less than what the cost would be if you are looking at the complications so this is a concept which is difficult to make people understand that because they don't really understand the cause that would be there when they are faced with the problem with the cardiovascular problem or renal disease so but this is something which has to be explained to patients and then only they can understand the importance of i mean sort of investing in their health and this at this point of time very right sir we always see that the upfront cost but we don't see the cost over a long term period and we also try to say our patient same that the treatment of diabetes is costly only when they are complicated not the routine ones uh another issue is that do we have to take precautions or which other drugs we can combine with the sema glutathione which we should be avoiding it yeah i think cloud yeah first thing is avoiding dpp before emitters there's no normal goal for adding db before any meter along with the same asymmetric when you're starting this molecule stop the db before any better now as compared to all other molecules yes it can go very well with the base insulin it can go very well with the with uh with metformin with uh with hdlt2 inhibitors also because they have uh synergistic effects there i mean in the sense that they have what good uh effects of both the molecules can be can be uh can be benefited i mean you can take the benefit of the good effects of both the molecules uh so i think the major ones that you want to avoid are the db between heaters and then you would give less preference to sus at that point of time because this this molecule also has a very good glucose loading efficacy but in those patients where you require additional glucose loading then probably you may use seo also right now only thing that you have to be careful about the hypoglycemia because of the potentiation of this issue right so what is your personal experience so far about using these drugs yeah this molecule has been very recently introduced in our country maybe just about a month since it is introduced we have a few patients but our experience also goes back to the clinical trials where we've been using this clinical trials where we have participated in the clinical transfer with this molecule and we have seen very good efficacy i mean although there you don't exactly know which patient is on the medication versus which patient is on placebo but overall we see that you know there is a good efficacy and uh tolerability has been good uh more than 70 percent of patients have been able to tolerate the 14 mg lows some have not been able to target the 14 mg dose so we continue with seven mg dose and they do pretty well with that can we use it in pregnancy or in type 1 diabetes yeah those are two situations where we should be avoiding the molecule and certainly avoid the molecule in pregnancy and type 1 diabetes and also in patients i think but for that it can be used even with significant renewal dysfunction also it can be used and with cardiovascular disease also it is preferred because it is not the advantages that in fact because of all these advantages the both the american diabetes association as well as european uh society of diabetes they have taken this drug much ahead in the ladder in the algorithm for initiation of the treatment algorithm this year i think in 2022 only the idea has changed the algorithm and has suggested that they can be used even before metformin that is if you have a person who has a car who presents with a cardiovascular disease has is detected to have diabetes not been on any medication for diabetes you can even start off with this these agents or even the sgt2 even before metformin is considered and in those who are metformin alone if they are if they are controlled with metformin have a cardiovascular disease have a need for this molecule you can stop the metformin and use this molecule so this is the current suggestion from the india while the european cardiology society was the first one to say all these in maybe two three years back but i think the ada has has made this change in this year's uh clinical practice recommendations they come out with every every january they come out with the standard of care ada i think the only that will compete it will be a cld2 inhibitors with this and acid may be taken up by the cardiologist but this drug will remain with the endocrinologist and the physician i believe true very true thank you very much sir you answered all the questions and it was real pleasure and honor to have you with us and would wish to have you on our platform for other topic of discussion of your address sometime in the future thank you so much sir thank you thank you very much for inviting me thank you thank you sir that brings to the end of our uh cutting edge stories so with this we come to the end of this discussion thank you sir thanks a lot thank you stay home and see us next week same time same place thank you good night you

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dr. Mahadev Desai

Dr. Mahadev Desai

Senior Consultant Physician | Ahmedabad

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dr. Nikhil Prabhu

Dr. Nikhil Prabhu

Consulting Diabetologist at Haut Diabetes Care, Ghatkopar ( west ) & Niranjan Diabetes Clinic, Goregaon ( West )

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dr. Rakesh Sahay

Dr. Rakesh Sahay

Professor & HOD, Dept. of Endicronology| Osmania Medical College & Hospital, Hyderabad.

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dr. Hasim Ahamed

Dr. Hasim Ahamed

Consultant Gastroentrologist, Lisie Hospital, Kerala

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dr. Mahadev Desai

Dr. Mahadev Desai

Senior Consultant Physician | Ahmedabad

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dr. Nikhil Prabhu

Dr. Nikhil Prabhu

Consulting Diabetologist at Haut Diabetes Car...

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dr. Rakesh Sahay

Dr. Rakesh Sahay

Professor & HOD, Dept. of Endicronology| Osma...

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dr. Hasim Ahamed

Dr. Hasim Ahamed

Consultant Gastroentrologist, Lisie Hospital,...

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