Obesity Pharmacotherapy: Now and Future

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Obesity Pharmacotherapy: Now and Future

11 Oct, 2:30 PM

welcome hello everyone thank you so much for joining uh welcome to yet another very very interesting session on Netflix I'm Dr Nija Kaka and uh at today's guest on Netflix is Dr Nita Deshpande she's a diabetes and obesity expert who has been serving her patients with her expertise for nearly or more than 20 years Dr Deshpande has graduated from JN Medical College belgaum with an MD in Internal Medicine a post which is also gone to get certified in diabetology and uh diabetology from University of Newcastle Australia and obesity from American Society of bariatric Physicians to top it all she's also an avid researcher and academician having published in several prestigious journals and having represented India in various International conferences as well uh cherry on the cake is just authored several of the textbooks on diabetology Obesity and she's a prolific reader as well she's been she's been invited to address and lecture of various conferences and physician lectures um several times so we are in for a treat uh today and today she Graces our platform to take a didactic session and present the future of pharmacology uh through future of pharmacotherapy for the modern epidemic of obesity uh so thank you ma'am for bracing our platform and let's begin the session over to you Ma'am thank you thank you so much for this kind introduction and at the outset I'm really thankful to Netflix for giving this opportunity to me to speak about a subject that not everybody is comfortable with both patients as well as Healthcare professionals and that is for macrotherapy for obesity so I'm going to in the next few slides talk about uh why we should use pharmacotherapy what is its role today and what's the future of this pharmacotherapy you will agree with me that obesity is now not just epidemic it's like a pandemic and it threatens to uh you know Mar or future because of so many other non-communicable diseases that obesity spawns and that's why pharmacotherapy may be an useful adjunct to other modalities of treatment in obesity so if you look at this slide you will realize that are we just treating weight loss that means are we just wanting weight loss with whatever treatment we're doing uh in a person who is overweight or obese definitely not and this slide brings home to you the fact that we are treating obesity we are not just creating weight loss because you have so many comorbidities that come with weight gain and obesity and you are attempting to treat all of that and only lifestyle modification or only just eating right just moving more may or may not actually impact all these other comorbidities that we're talking about such as hypertension or a fatty liver or uh you know obstructive sleep apnea Etc so because of all this please understand that what we're treating is a disease and that disease is obesity so it's not just a question of weight loss but you want all these other parameters also to get set right that is the importance of pharmacotherapy and I'm going to be dealing with that in a little more detail now if you look at this slide you can see that on the left hand side if you want a weight loss of up to 10 percent you have lifestyle modification honestly speaking lifestyle modification other than some outliers on a long term basis doesn't really produce more than 10 percent of weight loss it can in cases like 15 20 we have seen cases all of you know about Roy Taylor's studies where he has attempted 15 weight loss yes but on an average you would expect about 10 weight loss with usual lifestyle modification and then on the right side of the spectrum other end of the screen what you have is bariatric surgery so you have weight losses of 35 and more 20 30 35. now the Crux of the matter is that somewhere in between a failing lifestyle and again a a bariatric surgery that everyone may not accept or may not get actually somewhere in between you have a niche and that is an important Niche for pharmacotherapy and that is what I'm showing you here so the gap between an ineffective lifestyle modification therapy and an over invasive uh or rather what patients would perceive as invasive in terms of surgery in that Niche you have a pharmacotherapy now this pharmacotherapy is useful not just in that Gap but also if someone were to do behavioral modification or lifestyle modification and then later on there is a relapse there is the question of and I'm going to show that to you in the next slide as to why such relapses happen and then you will realize that this treatment Gap can very well be filled up by pharmacotherapy however we all know that there is a resistance to usage of pharmacotherapy both on the part of the patient and Healthcare professionals because it is perceived as being as having a lot of side effects and that the patient may not take it long term etc etc but I would like to stop people right in their tracks right here to tell them that obesity is a disease quite like diabetes it's chronic in nature and I want to tell you in the next slide why it was chronic in nature and why pharmacotherapy can help so when you look at the slide you realize why weight maintenance is challenging so you have a patient who's Come For the First Time who's attempting weight loss for the first time lifestyle modification is offered diet is awkward patient loses weight patient is Happy the doctor is happy this goes on for about six months maybe a year but by that time the internal biology takes over and then there are compensatory changes in the form of an hormonal imbalance in which the satiety hormones go down and the hunger hormones start to increase the hunger hormone is ghrelin which starts to increase post weight loss and the satiety of hormones like glp-1 Gip Etc they start to go down additionally energy expenditure starts to go down because the metabolic rate starts to go down and the Brain responds to food cues in homeostatic and reward regions that also begins to increase the reward center takes over so because of all these things what you find is that post weight loss a person starts to regain weight not because that person has lost his willpower lost motivation has become lazy but because hormonal metabolic adaptation takes place and Studies have shown that metabolic adaptation continues to remain for many many years which means to say that the patient's set point or the patient's new weight does not take over as that person's new weight and the metabolic adaptations can overpower that new weight at any time for many many years to come and the threat of weight regain looms large in many cases of Lifestyle modification in fact that's rather a rule no and not the exception and that is the reason that after weight loss in the first year second year the rates of relapse are so high because of this metabolic adaptation and that is where pharmacotherapy may help because the way pharmacotherapy works especially the modern drugs that we have today the way they work is that they try and overcome that metabolic adaptation so you need that little nudge or that little push with certain drugs which I'm going to show you in the next few slides which can overcome metabolic adaptations that occur post weight loss which are eminently responsible for weight regain and that the yoyo effect or the yo-yo dieting that happens with many patients of obesity that can be mitigated by the use of pharmacotherapy so that there is a smooth uh weight loss that can get sustained and that is why you must remember that weight maintenance by lifestyle modification alone can be challenging I'm not saying that it is never sustainable I'm not saying that it is impossible to maintain but it can be difficult and in these types of difficulty pharmacotherapy can give a helping hand and make it that much easier for the patient to maintain that lost weight look at the drugs that we have how do these drugs Act now we have in the brain basically two areas one area that has got a Gaudi related protein or agrp which is the one that is responsible for the person eating it increases appetite and on the other hand you have the pomc or cart neurons area which are responsible for satiety so or the drugs that we use nowadays or weight loss at the point these particular areas of the brain to increase satiety and reduce appetite so this regulation that happens in the high at the level of the hypothalamus at the level of the brain the central areas is responsible for maintaining the weight loss of course these drugs don't act just upon the brain they also act at various peripheral areas as well they can reduce gastric emptying and then they can reduce the intestinal glucose uptake increase the resting energy expenditure which is something that we want so these are the various ways in which weight loss can occur with the help of the different drugs that are available today however the history of weight loss drugs in the past has not been very encouraging in the past we've had many drugs that came in showed promise but then had to be withdrawn from the market for a variety of side effects that were totally unacceptable so this is the evolution or the history of safety or rather the loan safety of anti-obesity medications very very early on we had phenfloramine and dexplan fluoramine which had an action which was serotonergic and anorectic however we all know the story that was cardiac valvular insufficiency pulmonary hypertension and they had to be withdrawn then came subutomine and I have used subutramine I've done clinical trials with semitramine it was very very promising but it increased non-fatal myocardial infarction and stroke increase the heart rate and therefore that was also withdrawn from the market then came Ramona band which was also again very promising however it caused depression there was suicidal ideation and this also had to be banned and the last drug that very recently got taken off the market after showing decent promise was Lord Carson and this again caused depression suicidal ideation palpitations Etc and had to be withdrawn so you see that one always would treat such anti-obesity medications the newer ones that come into the market with a pinch of salt so you would always look for good amount of data enough number of patients that it has been tried on and then you would want to even think of anti-obesity medications only because of this history that I have shown you that so many came in showed promise and had to be withdrawn as you can see here now these are the drugs that are available in various countries out of all of these the only one drug that is licensed for use for obesity is orlistat in our country but the other drugs other than Lord Carson which was of course withdrawn all the other drugs that you see here in various parts of the world they are allowed to be used and you can see here the estimated weight loss that is drug minus the placebo not the total weight loss but the minus the placebo and you can see that uh for one year or so you can see that Phentermine topiramic Phentermine alone or not a Naltrexone with new propion these are drugs that are used have been used for one year and have met with uh variable success quite decent success and they are used in different parts of the world but we don't have them uh in our country except for early stat and you can see here very clearly that oddly start even with 120 milligrams Thrice daily uh the weight loss that you get at the end of one year is pretty dismal it's just about three percent which is nothing which even a lifestyle modification can do and that is the reason that I'm not a big fan of early start for this reason of course there are certain places where you can use it as you know as a customized way and I'm going to show you how you can customize therapy in uh obesity but all student done the weight loss is very very modest with oddly stack as you can see so then came the era of the glp-1 receptor agonis as all of you know when glp-1 receptor agonists were first introduced they were introduced as anti-diabetic agents because they got a good response you got a good response with the HV A1C reduction but then so many studies so many cbot trials were done and what they realized was that it can give substantial weight loss so then there was an exploration there were studies for trying to use these glp-1 receptor agonists in patients who did not have diabetes solely for weight loss and they did meet with success because as we know the glp-1 receptor agonists they act upon the brain where they increase satiety and the energy intake is reduced of course they act at the level of the pancreas and at the GI tract they reduce gastric painting and that is another methodology by which they can actually uh help to reduce weight and the the series of studies followed and uh today uh little glutide three milligrams and semiglutid 2.4 milligrams in the U.S at least is licensed for use for obesity even without a diabetes so liveroglutite is used in treatment as three milligrams uh this is a much higher dose than what is allowed uh only for obesity and semoglutid 2.4 milligrams once weekly injection so both these are injections little glutide is something that's given every day whereas semiglutite is given as a once weekly injection uh the method of action the mode of action is more or less the same there are half-lives differ and that's why you have one which is uh you know once a week and another which is uh every day and all of you are quite aware of these studies so the glp-1 receptor agonists I already told you have multi-factorial effects their effects on the pancreas are very well known and we have little glutide the leader study which told us that it reduces cardiovascular risk and in fact it is now in the guidelines that you must assess the ascbd risk rather sterotic risk and if a person is at high risk one of the first drugs that you would use is Lira glutine so cardiac function is improves systolic blood pressure is reduced inflammation is reduced so this is these are different actions like I told you right in the beginning you don't just want to reduce weight you want all those other good effects uh on diseases that obesity brings now the effects that you see on the right side on the brain are the ones that we are interested in for obesity for microtherapy and that is the reduced weight reduced by reducing food intake and increasing satiety by acting on the pomc and the other part of the brain uh because of which the satiety is improved and as I said the gastric empty is also reduced so this is how it is now when all this if you look at all the cvot trials with the different glp-1 receptor agonists they all found weight loss so the the studies were not designed to look for weight loss but however it was looked at the observation was that there was good bit of weight loss with all of them some a little more and some a little less and these are kgs lost versus the placebo so it is Placebo uh extracted uh weight loss that you are seeing over here and the last uh bar that you see is oral semoglutide which I'm going to come to in a little while so these were the trials done with lyriclotide as you can see the First Column shows you lyrically in obesity and pre-diabetes without type 2 diabetes and in fact I was a part of this clinical trial and you can see that there is an eight percent change in body weight at the end of one year and there is 80 reduction in the risk of type 2 diabetes over three years so some kind of a preventive aspect also has been studied here then of course you have the scale diabetes the scale maintenance and the scale sleep apnea which is not pure obesity but of course obesity was a Criterion for enrollment even in these particular studies so you can see here that with three milligrams of later glutide every day the efficiency of Lira glue type to reduce weight is very very good it is sustainable as you can see in this particular so 56 weeks one year this is the durability that you have seen there are additional benefits with glp-1 receptor agonists as per trial data and you can see here that this is a meta-analysis and there is a reduced all-cause mortality with grp1 receptor again is compared to Placebo which is very important for us as a pleiotropic effect and importantly we all know that fatty liver and Nash is the root cause of many non-communicable diseases and that is also favorably affected by Laura glutide versus placebo as seen in this particular slide now we come to the most recent approved Innovation which is semi-glutite so I would go into the details of the molecular structure of some of you type but I will also I'd like to tell you here that it is 94 homology with the human glp-1 and semiglutid is in the news today because uh the 2.4 milligrams of semi-glutid once weekly has been approved by the FDA quite some time back as a treatment for obesity even without diabetes just pure obesity and the man many facets of semiglutid are seen in this particular slide and you can see here that uh it has an oral bioavailability uh there is dpp4 stability so many attributes that it has and it is human glp1 based and uh you can see that it can bring down the blood sugars it affects cardiovascular disease favorably obesity of course it brings down weight then in non-alcoholic fatty disease CKD and perhaps there is a hint that it may improve cognition and uh a future use of it may be for Alzheimer's disease not right now we don't have enough data but the fact is that semiglutide has got several fasts to it and it has several uh attributes to it in multiple pathways and SEMA mutated 2.4 milligrams for obesity was studied in what we call the step trials the name of the entire program is the step program and the primary endpoint of the step program here it was not glycemia that was looked at but obesity was looked at because the primary endpoint for all the step trials is made so you had the step one to step four then step five step six various combinations were done and across all the step trials treatment with semiglutid was 2.4 milligrams once weekly subcutaneously and it was compared to Placebo as an adjunct to Lifestyle modification and only in the step three which I want to show you a little more in detail lifestyle intervention was intensive behavioral therapy backed so it was not just lifestyle modification but even behavioral therapy was used and that was the step three trial in which there was an initial eight week low energy diet and a higher Target for physical activity so that was the step three so these were the different trials the step program what we call your semiglutite 2.4 milligrams once weekly subcutaneously was used and examined and this is what you can see across the board what you can see whether it's step one step two step three up all the way up to step five also what you can see is that there is very good weight loss if you look at the percentage of weight loss across all these trials whether it is with behavioral therapy or whether you're looking at sustained weight management where you're looking at even in the maintenance period or even in the step five which is a two years weight management program you find that anywhere between 15 to 17 percent is the weight loss let me remind you here that if your target for weight loss is just about five to seven percent lifestyle modification is good enough but if you have a lot of comorbidities like diabetes hypertension fatty liver Etc five to ten percent weight loss may not be enough and what you require is anywhere between 10 to 15 weight loss or all these ncds to become better and as weight loss increases this data now to show us and as weight loss increases to more than 15 percent of the existing weight more than 15 percent that is the time that you can get incremental benefit in the form of reversal or remission or certain in series so up to 10 is lifestyle modification and all you can you can just get a good glycemic control or you can just get good health but any comorbidities are present up to 10 weight loss may not be sufficient and you may require up from between 10 to 15 for microtherapy fits in very very nicely more than 15 weight loss I'm going to show you some drugs which can produce even that and then that is the time that you get an incremental response so you can see here that with 2.4 milligrams once weekly of semi-glutide across all the step trials what you get is a 15 to 17 weight loss which is phenomenal which was not there with any other weight reducing drugs so far even the ones that got banned none of them produced between 15 to 17 weight loss so this is that particular step three trial which is semicuted 2.4 milligrams its efficacy with intensive behavioral therapy and this is the one that caused 16 weight loss it was a double blind randomized phase 3A trial with BMI more than 30 or BMI more than 27 with comorbidities but not diabetes because this was a non-diabetes trial so that is the important thing to understand over here so this is the overall summary of 2.4 milligrams of semiglutyride ones weekly and it has been investigated solely for weight management to reduce energy intake and control appetite and all together the step one to four included five thousand and not patients so you have a huge database here and it showed a mean weight loss as a set of 17 to 18 in subjects without diabetes and effective double-digit weight loss in subjects with diabetes and it is effective in inducing weight loss there was a study this step uh the third one that I showed you where maintenance of body weight also was there and improved cardiovascular risk factors if you look at the safety profile it is very similar to all other glp1 Ras and there was no new safety concern so the cvot also if you look little gluten and semi-glutid you find that there is no signal for any increased uh cardiac risk or anything of that they're pretty safe in that particular respect again importantly uh there was significant reduction in base circumference which is a surrogate marker for visceral adiposity and you know that that is the bad fat and if bad fat is also reducing with pharmacotherapy it's a double bonus because it's not just weight loss but you're also getting reduction in visceral adiposity which is so very important for us and that was seen in these particular studies now came what they call the game changer and that was oral semicutide you should understand that some or until up until this molecule came in all of the glp1 RAS were injectable although some of them were only once weekly a little tight is every day but they were all injectable and we know the acceptability of injectables is not so good and that is how oral semiglutide came in it's a new route of administration of any jlp one ra ever and it is an innovation and first in class so the possible uh with they have used what they call an absorption enhancer and that is the technology that has been used and that's and hence they have ensured that absorption can happen so they came up with a a program of different trials studying different aspects of it and that was the Pioneer program so with diet and exercise the Pioneer one uh the oral samaglotide was versus placebo in Pioneer 2 it was pitted against sglt two Inhibitors in Pioneer 3 it was used versus dpp4 in Pioneer 4 it was used versus glp1 receptor administ or Placebo and then Pioneer seven so different varieties of patients with different medications all of them were tested for uh with oral semi gluten please remember that as of now oral semiglutid is not been licensed for use anywhere in the world uh only for obesity it is always with diabetes diabetes with obesity it has been licensed for use and that is why all the studies that you're seeing here are with different anti-diabetes agents and that is the Pioneer program and if you look at this I've summed it up in one slide you can pinch it out for a better View and you will find that whether is monotherapy or versus empathy Frozen or cytogliptin or letter of gluten various permutations combinations you will find that uh progressively from three milligrams because that is the dosage of oral samagutide from three milligrams to 7 to 14 you find that the highest weight loss is with protein and even if it is used at seven it is still higher than all the other uh comparisons that have been pitted against it so whether it is with Emperor or whether it is with Sita you can see that everywhere the A1C is better and the weight loss also is better the upper panel talks about the hpa1c and the lower panel talks about the weight loss because I told you it is to be used with diabetes and obesity and you can see here so we clearly that it scores over all its other competitors against which it was compared so the Pioneer study gives us robust evidence that both A1C and body weight are very effectively reduced with the differing uh with the increasing doses of oral semiglutid as you can see here so you could get an A1C reduction of up to 1.5 percent and weight loss up to 5 kgs so this is the safety somebody across all the Pioneer trials and you can see that there is a large safety database for oral semiclutite more than 5700 patients have been exposed to it most common as usual uh the Adverse Events were gastrointestinal but mild to moderate in severity and at short duration of action and there was very little propensity for hypoglycemia of course unless it was used with insulin there were no new unexpected findings it was well tolerated quite similar to other glp-1 receptor agonus now coming to now I have given you an overview of all the drugs that we have available today so I'm telling you a few hints on how you individualize obesity pharmacotherapy we always talk about individualizing diabetes therapy now I'm talking to you a little about individualizing obesity pharmacotherapy if somebody is there with coronary artery disease pre-diabetes and diabetes you would like to use either liver glutine or semiglutide of course there are contraindications like a family history of medullary thyroid carcinoma or a personal history of pancreatitis so this is so with diabetes and coronary artery disease you would want to use leroglutide or semilutite supposing if Naltrexone bupropion was available and the patient is a patient who has lacked so many of these patients have if there is depression or those who want to stop smoking then though or who have food addiction and Cravings actually food addiction so any kind of addictions then you might be better off trying to use this molecule only start as I said uh is not really too effective unless there is someone who doesn't want to take a drug that acts from the brain and acts on the different organs and acts at a local level then maybe you want to give this or somebody who has got a very high fat diet then maybe it is useful so this is like individualizing it phenter mean Topiramate patients with chronic migraines and obesity uh this might be more helpful for them there are contraindications like uncontrolled anxiety depression cardiovascular disease Etc so you have to be careful you know the pros and cons of course we don't have it here but just for completion sake I'm telling you how one can individualize obesity for microtherapy should this be available in that particular country now I am going into the future I am talking about an absolute game changing new molecule which is also called a twin why a twin because it is a glp-1 Gip receptor dual Agonist so two incretings are what it uh acts upon or is a Agonist for and that is why it is also known as a twin it's a multifunctional peptide and it has shown amazing results I am going to show you some of that this is the newest kit on the Block and it has especially in the American Diabetes Association this year it has made waves actually for the data that it has thrown up the mean Half-Life is five days and hence this drug also can be given as a once weekly dose but it is given uh subcutaneously is an injection and there are trials in type 2 diabetes and there are ongoing transfer obesity four to five trials have been completed already and published as far as type 2 diabetes are concerned with obesity and there are ongoing trials for obesity one of them is already being published so this is the surpass program where it is appetite the twin was used in type 2 diabetes so I am showing you data of surplus one two and three over here but the Surplus 5 and 6 has also been done and what you can see here is that with differing or increasing doses of disappear of 5 10 and 15 milligrams you can see here that whether it is against Placebo or whether it is compared to semi-glutid one milligram which is what you give for type 2 diabetes or whether it is in comparison to insulin degree deck look at the change in body weight percentage-wise so in kgs rather so you have got an immense amount of weight loss as compared to Placebo as compared to semiglutite and as compared to insulin degree deck in which of course the weight increases a little bit because it is of course insulin so this is the surpass program where it is the peptide is used in type 2 diabetes with obesity then comes this important seminal trial which is called the sir Mount one trial this is the first trial in the Obesity program of tilzepetide where tissiperite is used once weekly for the treatment of obesity it is a phase three double blind randomized control trial and the objective is to assess the efficacy and safety of the zipper type a novel twinkle and glp-1 Agonist in the treatment of obesity about 2000 500 and odd patients people with a body mass index of 30 or more or 27 with at least one comorbidity but not diabetes please remember that for obesity pharmacotherapy the international guidelines are the same that is you have to start pharmacotherapy if the BMI is more than 30 or if it is 27 or more with one comorbidity of obesity that's when you can actually start a pharmacotherapy in reality this does not happen but these are the international guidelines and this appetite five milligrams 10 milligrams 15 milligrams in this particular trial was compared to Placebo and the primary outcome that they were looking at was percentage change in body weight with the 15 milligram dose and what you can see here is a 20.9 weight loss as compared to 3.1 of placebo now this is phenomenal because 20 weight loss goes somewhere close to bariatric surgery in fact and weight reduction they also looked at the primary outcome of weight reduction of at least five percent so 91 of people in the terzapatite group lost at least five percent of weight as compared to 35 percent in the placebo and the secondary outcome was Adverse Events caused treatment discontinuation so discontinuation was in 6.2 percent of patients versus 2.6 in Placebo so the conclusion of this surmount 1 trial which has uh been actually published very recently it is a 72-week trial not just a one-year trial in participants with obesity where they use three doses 5 10 15 once weekly and they go what they got as a result was substantial and sustained reductions in body weight so if you look at these uh different graphs I would request you to just concentrate on the a part of it that is the top left graph that you see so you have five milligrams 10 milligrams 15 milligrams and Placebo and what you see there is 20.9 percent of weight loss at the end of 72 weeks and this is in comparison to Placebo then they've looked at other uh uh indices such as the body weight reduction Target and also percent change in body weight by that time and I'm going to show this to you a little more in detail this is the the proportion meeting weight loss Targets in surmount 1. so if you look at this very carefully what you find is that more than 85 percent of trial participants lost more than five percent body weight at all doses so even if you'd use just five milligrams of uh principle type 85 you know people lost more than five percent of body weight again more than 50 percent of patients lost more than 20 percent of body weight now 20 is huge and half the patients at 10 milligrams 15 milligram doses that's why I said that it has been one of the most talked about molecules in recent times and Adverse Events were of course similar to glp1ra and included dose dependent nausea and vomiting mainly during the dose escalation part and the nausea and vomiting is actually attributable to the glp1 part of it and not the Gip part of it actually the giac be part of it reduces nausea and the glp1 part of it increases no share so they actually need to negate each other but that didn't exactly happen and there was nausea and vomiting especially during the dose escalation so that was about disappeared something to watch out for sermon two sermon sermon three are again uh trials that are being done with the zipitide and the results are going to be out by early 2023 so there are more number of Trials and they are there are head-to-head comparisons with other glp-1 receptor agonists Etc and that is in the offering so this is a drug that we need to watch out for especially for obesity because the exciting part is 20 weight loss in more than 50 percent of trial participants which is very very exciting this is something new it is going to come in future the clinical trials are underway and that is an amylene analog called kagrel intide plus semoglutile used together preliminary Studies have shown that cagligent type alone versus semaglutid alone versus this combination versus placebo it was found that the combination worked best it was addictive synergistic so greater weight loss with calculated more than 0.3 plus semicutide than with SEMA alone or with Catalan type alone so this is something that is underway and it is going to uh you're going to start seeing the results very soon uh maybe in the next few years you are going to see results of this combination of Catherine and tight Plus semiglutide so to summarize weight loss improves Associated complications we all know that and that's what we want maintenance of weight loss as I showed you can be difficult due to compensatory biological mechanisms which we call metabolic adaptation that encourage weight gain and the adaptation stays for a long time emerging pharmacotherapy options work when modifying body weight regulation as I've already shown you I've shown you a slide as to at what level these drugs act at new developments in the therapy for obesity management that complement our understanding of genetics and biology of obesity so as I said the twin is on the horizon and it has potential for weight management with obesity with and without diabetes finally please understand as Healthcare professionals that obesity is a chronic disease requiring lifelong treatment I already just had a glance at one of the questions which come which came in that how long should we use it I'm going to answer that a little later but please remember obesity is a chronic disease just like type 2 diabetes and it has many cardio metabolic osteoarticular and oncological morbidities which you should not forget there are a number of treatments that can be successful if used judiciously diet and exercise should of course Remain the Cornerstone of obesity but you may have to supplement it with pharmacotherapy some cases bariatric surgery depends upon case but Case by case it is critical to respect the patient and involve them in their obesity treatment planning explain to them counsel them that obesity is a chronic disease treatment is lifelong whatever you give them things are very very important for us to understand and that is what we should be doing and do not we should not hesitate to use pharmacotherapy when we have it so it is not a cosmetic issue it is a real metabolic issue so we have to be very careful and explain to our patients we need to be convinced first as Healthcare professionals and then we will be able to convince our patients that it is a long-term process so I thank you all very much for watching and I'm ready to take in thank you so much ma'am for an engaging yet such a comprehensive session uh we shall take some comments and queries that have come as a lot I can imagine just a moment here doctors uh firstly Mom thank you so much thank you for teaching us so beautifully about a topic and just breaking it down simpler and simpler making it so easy to understand for all of us we're going to give our doctors a couple of minutes to put in their questions here in the comment box so let's start with the questions [Music] um we can start with Dr Ramesh Kumar as well as Dr Ansari shafiya anjum tayab Hussain both have asked how to manage psychotropic induced obesity well uh that is a very uh different kind of uh very specialized kind of obesity and it is Case by case basis so uh we can of course try to use these drugs also in them but that is not simple obesity what of course obesity is never simple but uh this is what the drugs that I have told and everything that I have talked about is basically for cases of simple obesity provided you have kind of assessed the patient for any genetic causes any of these special kind of cases and then on a case-by-case basis they have to be assessed and treated control um also uh Dr Ramesh Kumar has asked again does glp uh do glp against stabilize endothelium well we don't have any uh data as such where endothelial dysfunction or inflammation has been studied but going by the metabolic parameters uh I'm not aware of any biomarkers that have been studied for this but uh yes little glutide has been licensed for use as a drug that can reduce acvd risk and it is an ADA ESD guideline and so definitely it could be stabilizing the endothelium and that is why it is shown such results where it is beneficial in reducing the cardiovascular risk all right um again Dr Ramesh Kumar has asked cost of semi-glutile and duration of treatment right so yes it is expensive uh in India today uh we have oral semiblutite we do not have the injectable one the oral semiglutid costs around 300 to 350 rupees per tablet and it is for how long I've already answered that that it is long term lifelong I don't know but on a long term basis definitely because if you stop it there is a trial actually where you can see that you stop a glp-1 receptor Agonist and the way it starts to go up again which is true of any chronic disease you stop therapy you relapse so that is going to do this so you stop lifestyle modification also you relapse you stop the drug also utilapse are there any drug uh contraindications or interactions with glp again Dr Ramesh Kumar results right so uh it is there on the package Resort you are not supposed to use it in anybody who has a history or a family history of medullary thyroid carcinoma you are not supposed to use it in anyone who has a history of pancreatitis because there could be a red flag in these but other than that uh there are no basic contraindications and such there are some cases of a little bit of a worsening retinopathy for person already has retired of the team so these are some of the cabinets that are there for glp-1 receptor items all right thank you ma'am Dr Vikram pawar has asked as many GPS have not used oral samglutite can you elaborate on how to initiate uh the dozing and the up titration of the doors and relation to meal also is there added benefit in Sugar control if used with oral dpp4 inhibitors so these are very good questions very practical questions so oral semiglutite comes in three strands that is three milligrams seven milligrams and 14 milligrams you're supposed to start with the lowest dose and up titration is done once in every four weeks because uh the tolerability can be an issue so whichever strength you are using the three milligrams start with the three milligrams it is always to be given on an empty stomach first thing in the morning with precisely 120 ml of water not more than that otherwise it's not effective and for 30 minutes after taking the tablet there has to be no intake of anything at all if a person needs to take thyroid medication it has to be taken after that half an hour so this is the methodology of taking it you titrate it after four weeks to seven milligrams watch it and then again so this is how it is to be done and I think the second part of the question was can you use a dpp4 inhibitor with it it is absolutely uh um useless to use these two together the reason being that both belong to the ingredient family and dpp4 inhibitor acts uh in a milder Way by just increasing the endogenous glp1 prolonging the action of the endogenous glp-1 whereas by giving analogues you are giving Supra normal levels of glp1 so what is the dpp4 going to do so it's up to you so you don't you never combine them so if you want to start a jp1 receptor Agonist you must always withdraw the dpp4 inhibitor because it is of no use you're already giving such high doses of glp1 so you don't need the DPT for people thank you for the answer ma'am uh Dr Sumaya Abdul Kalam has asked is there any contraindication to use semi-glutides for patients with retinopathy yeah I already just alluded to that that you will have to really watch it if you want to give it if a person already has retinopathy where worsening has been seen in some cases so you have to be very very Vigilant maybe if it is just early background diabetic retinopathy well controlled and all of that you could give it but you have to watch it okay uh uh the thing we have Okay can metformin be used for obesity without diabetes has been asked again by Dr Sumaya petivala yeah so this is an often asked question whether metformin can be used as an anti-obesity medication well the results have been very very dismal uh there are few patients who have quite a bit of weight loss but they are the outliers if you look at a whole mass of people and if you look at the trials metformin doesn't really cause much weight loss it's quite disappointing as an anti-obesity agent okay Dr Ramesh Kumar has again asked uh does uh semi-glutid improve hypogonadism in obese patients most of the comorbidities improve but particularly hypogonadism is not something that I have looked at honestly speaking so maybe if we go into the details of some of the studies that have been done it could have been one of the parameters that have been studied but I'm not exactly sure which one all right uh Dr nirmala has asked if uh intolerant to 14 milligram of semiglutide can we continue with three by seven milligram dose three or seven milligram doors yes absolutely I've had patients like that in whom I have used three gone up to seven at 14 they have started to have intractable GI symptoms and I've had to down titrate them back to seven milligrams where they are comfortable so yes if the side effects are absolutely incapacitating then we we do down titrate and come back to the lower dose so the lowest tolerable dose or the rather the highest tolerable dose is what you should be using has asked what about vomiting on oral semiglottite 15 milligram yes it's there all the GI symptoms are there so you have you can have nausea and vomiting as the prime symptoms uh you in the first four weeks you can give some symptomatic treatment because it is expected to Abate after that most of these uh GI symptoms do await uh after four weeks they start to go down and then the patient becomes comfortable until that time to tide over that period you can start give symptomatic treatment all right now uh uh Dr shubham vasudeva has asked can depoglyphosene be used in obesity without diabetes no it has not got I mean there are some trials underway but as of now it's not licensed for use but there are some trials underway for its use as an anti-obesity medication but we don't have any data yet so ma'am all these off label drugs uh their usage like bupropion and Metformin there are a lot of questions about these so do they have any role in pharmacotherapy of obesity without of the primary uh disorders disease being present in the patients yeah you one people do use it off label for one thing but the effectiveness of bupropion used alone without a Nitric zone or just Phentermine people do use it and in occasional cases uh if the weight loss to be had is uh the weight loss goal is low it has helped but then again it is an off-label use so people do use many of these drugs in fact uh little glutide if it is used in obese patients in India or some are gluten oral used for obesity in India is all off label if at all people are using it right because as I said on label only only start in India as of today so uh whatever is used probably is off label of course things may change in times to come very soon and we may have one of the glp-1 receptor Agonist that can be approved by the dcgi for obesity alone and then we are good to go as far as the glp-1 receptor Agonist is concerned will be very useful for us has asked antioversity medication for patient on medications like acetylopram that causes weight gain as a side effect basically drug-induced obesity yes so uh as a blanket statement I would say that uh we share about drugs especially antipsychotic antidepressant drugs that cause weight gain it is always wise to talk to the psychiatrist and try to get them to use a drug uh which causes less weight gain or no weight gain and they usually oblige and they try to you know change it over especially if a person is putting on a lot of weight so those issues have to be sorted out first before you can actually give anti-obesity medication otherwise it's of no use giving anti-obicity medication and then giving another medication which causes a lot of weight loss a weight gains uh Dr yogesh panjay has asked products like Herbalife are products like hobby life useful is there any schematic guidelines for the management of obesity like hypertension uh diabetes diabetes well uh since he's this person has used a particular name I would like to direct this person to several uh reports that have come in uh prestigious or peer-reviewed journals where a lot of hepatotoxicity has been seen with this particular drug so with this particular uh formulation this Herbalife and it is not medicine it is they they uh you know propose it to be used as uh some kind of uh uh replacement or uh you know calorie reducer and things like that but there are enough and more reports which talk about uh its contents causing uh hepatotoxicity there have been a few deaths in fact and this is there in the journals to see so this is not something that we would advocate for weight loss and definitely not weight losses of 15 and 20 that you get with pharmacotherapy uh Dr Ramesh Kumar has asked what about exynatite yes excellentide is good it gives good weight loss but now it is excited is usually used twice daily of course there is a once weekly xenotype also uh but now we have better molecules and now we have the oral one so anxiety of any kind is not licensed to be used for obesity in any case anywhere in the world not just India anywhere in the world it is not licensed to be used for obesity so when you have drugs like now you have two injectables and once weekly semiglutide both licensed for use in the U.S for obesity so why would you go back to internet right ma'am your session has been praised extensively in the comments section as well through all of these medications in pcod treatment I saw the question a couple of times I've been somewhere earlier as well so that that's a very valid and a very important question good that it was raised so it hasn't been studied particularly in PC only but yes it will be useful in pcod because I have shown you some data where it can prevent diabetes from happening it's been used in pre-diabetes and it can reduce weight very nicely and uh it has a role in pcod related obesity for sure for your closing notes yeah thank you very much to this and uh obesity pharmacotherapy is a science by itself it has to be Mastered by all of us because obesity is a pandemic and it should be readily acceptable because there is enough data and it is scientific to use obesity pharmacotherapy in the appropriate cases the use of it should be judicious so it is here to stay by so we should all become very well versed with its usage and on how to counsel patients for obesity pharmacotherapy so that we are able to beat it but having said that my bottom line and my uh takeaway thought would be diet exercise behavioral modification lifestyle modification are the Cornerstone they can never be given up even after bariatric surgery so it is there for all time to come and that is lifelong so thank you very much for having me here thank you so much for giving us your time we thoroughly enjoyed learning from you we hope to see you many more times of Netflix my pleasure thank you thank you thank you


The obesity pandemic continues to grow at an alarming rate. Because lifestyle modifications have been limited in their success in weight loss maintenance, pharmacotherapy plays an important role in achieving clinically significant weight loss and preventing the development or exacerbation of comorbid conditions. The plethora of on- and off-label AOM's(Anti obesity medication) creates the unique challenge for physicians to decide which medication may be most appropriate for the individual patient. Interestingly, Tirzepatide has also been investigated for the management of obesity in individuals without T2DM. Dr. Neeta Deshpande, a renowned expert on Diabetes and Obesity, aids us in our understanding of obesity and associated Mx.


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