Diabetes: Drug Therapy

We welcome back our audience to MedPods, the podcast on topics of medicine from the Department of Internal Medicine at AFMC. This conversation that we are having today is going to be a follow-up of our earlier discussion on the topic of diabetes mellitus, in which we spoke to the commander Sandeep Kumar, associate professor in medicine and endocrinologist in the department. Welcome back, Sandeep. Thank you, sir. Today, we are going to talk about following up on our previous conversation on diabetes and take the discussion now on to treatment of diabetes. We considered the various aspects of non-pharmacological means of management in detail in our previous edition. Today, we shall dwell deeper into the drug therapy of diabetes and I understand how complex it is, as far as the way pharmacotherapy of diabetes goes, just because we have so many drugs and newer being added every day. So what I would expect that in this conversation, we shall first talk about the various drugs, the various groups of anti-diabetic drugs starting from the oral anti-diabetics. And then we move on to certain newer molecules, which are now in practice. And then we will culminate our discussion on these drugs, brief discussion on various types of insulin. So I now want you to dwell on these oral anti-diabetic drugs. Sir, once we have discussed the non-pharmacological management of diabetes, yes, so when we have given the non-pharmacological advice to the patient, we will progress to starting the patient on oral anti-diabetic drugs. And what is there? We have host of drugs and for the management of diabetes since age old and we have a lot of experience with respect to their use. And also because just by virtue of prevalence of diabetes, there's a lot of research which is going on with respect to this and we keep on adding, having the newer drugs almost every one to two years and with this, the drugs available in our momentarium are many. And just to summarize, all of these drugs have their advantages, but yes, with like with any other drugs, they do have certain adverse effect as well. And whenever we are choosing, we should keep this in mind. So just to tell about the older version of the medicines, drugs which are available. So first one would be bygunives and the metformin is the one of the most important drug. In fact, I would say this is the biggest gift which the scientific community has given to the mankind. It has been, we have a lot of experience easily available, very effective and it has you know benefit which is beyond diabetes and it has been seen that metformin can cause HPA1c reduction which can be more than about 1% in our practical scenarios. And then we have other drugs which also has been used for very, very longer durations and these are sulfonylureas. And why this drug is important to remember because the HPA1c reduction capacity is also high like and the drugs which are under this headings are glipipride, glipizide, gliburide and they can also reduce HPA1c significantly to the tune of 1%. However, in our practice, we all our students should remember that whenever you are using such drugs, since they are sulfonylurea, they are scretagox and what do we understand the scretagox is that they increases the insulin secretion from the beta cells. So once they increase the beta cell insulin secretion, these have propensity to cause hypoglycemia and in our practice we do see, you would agree that there are certain people, we do few of the people we see who land up with hypoglycemia with over treatment or overdose or when we are not titrating in the well, titrating the sulfonylurea as well and I forgot to mention about metformin. So metformin is a beautiful drug which has low chances of causing hypoglycemia and it increases the insulin sensitivity. What does it mean that it increases help in entry of the glucose into the muscles and fat by increasing the expression of the blood for and also it activates AMP kinase in the love liver and decreases the glucose production at the liver level and hence this drug is a very beautiful choice in management of the diabetes. Mollitus in fact, certain authors also call it reculant to the exercise and why so because it increases the insulin sensitivity. Then sir, we have thysolidinidions and it has been also being used for very long durations and the drug which is under this is bioglutazone and again this drug is beautiful in the sense that it reduces the insulin resistance, it is helpful in certain, helpful when the setting of the stroke and all it can be used where it can demonstrate certain benefits and however we have to be careful with respect to fluid overload especially in the patient who are in the heart failure etc. And there was a concern regarding urinary bladder cancer earlier with this drug, however it was refuted by the subsequent studies and then it can also reduce the HVA1C which is mild and which could be through the tune of less than 1% and we have alpha-glucosidase inhibitors A-carbose megalitole and we do use it in a day to day practice but their capacity to reduce HVA1C is only limited to about less than 0.5% but yes in the appropriate setting they are useful and how do they act that they prevent the breakdown of the complex carbohydrate into the absorbable or simplified carbohydrate and hence in the when the patient is not getting having a post meal excursion or specifically than patients then they are not obeying dietary advice which we have discussed in a previous talk, we can add these drugs in them and then they are also safe. We also have megalitonid analogs like naticlineid or epaglineid, they can also be used and they also are kind of scrittagogs because they help in the potassium mediated, they act at the potassium channel at the beta cells and helps in insulin secretions and they also have mild to moderate HVA1C reduction capacity. We also have DPP4 inhibitors and SGLT2 inhibitors, GLP1 receptor agonist which are newer drugs which do have their benefits and yes we would be as you told we would be discussing as we progress towards today's podcast. So it is very confusing for a person who is learning this subject to start with. So the students must understand that it is always important to start with history and as you rightly mentioned starting off with metformin onwards these are the drugs that are very routinely used, they have a great advantage that they are less expensive and have moderate efficacy which is high saying that things like sulfonylubia or metformin and in Indian context where carbohydrate intake is so high the alpha glucosidus inhibitors also become an important drug by reducing the post-prandial glycemia. So over the last decade or two we have had newer molecules coming and in that the DPP4 inhibitors were first to come when we looked at the incretin pathway and thereafter we had newer drugs like GLP1 receptor analog also which work through the incretin pathway. So I want you to tell our students what does incretin effect mean and how is this pathway manipulated by these drugs. So there was a very beautiful observation which was made in year 1932 by Bara Hetal and what they observed is when the equal amount of the glucose was given by intravenous root and oral glucose very, very surprisingly the insulin secretion was higher when the glucose was given by the oral root. So it was this concept intrigued them then they further investigated and they found out that it was a certain hormones which was secreted from the gut and these hormones were going to the pancreas, stimulating the beta cells and also to some extent the alpha cells as well and it is causing the glucose stimulated it means oral intake after the intake of the oral glucose it was causing the more insulin secretion and later they gave the name to these molecules and these mediators were number one is GIP that is glucose dependent insulin tropic peptide which was secreted from the proximal intestine from the K-cell and another one was glucagon like peptide 1 that is called as GLP1 and that was secreted from the distal part of the intestine and this concept was most very, very phenomenal finding with respect to diabetes research and this is being now you know researched to the very great extent because it is not only the glycemic benefit which you know the memetics of these molecules are giving us but also you know the benefits beyond the glycemic or glucose reduction with respect to you know benefit with reduction of the even weight, obesity, hypertension and reduction of the cardiovascular risk as well. Ya so that was very interesting because unlike the other secretrogogs which we had classically like sulfonylurea which would cause insulin secretion irrespective of how much your blood glucose was and hence led to hypoglycemia these drugs although they cause release of insulin they do it only when there is hypoglycemia and that makes them prone to cause less hypoglycemia or almost negligible hypoglycemia and that makes them wonderful drugs and unlike sulfonylurea they also do not cause weight gain in fact they cause weight loss with GLP1 receptor agonist so that has made them promising molecules of this decade. Now another group of drugs that we have actually been found to have great advantage and it has probably the latest group that we are actually using are the SGLP2 inhibitors. These are drugs which do not act either through insulin or pancreas but they have an independent mechanism of action so can you elaborate on them? Ya so this is another group of drugs which is very very important in the diabetes management and this is called as SGLP2 inhibitor so let us understand how we discovered SGLP2 inhibitor so what happens is that the glucose is you know the excluded from the glomerulus and the entire glucose is reabsorbed we very well students can recall that we have a renal threshold of 180 milligram per deciliter and in the normal individuals we do not have any glucose in the urine. So what is happening once the glucose is filtered large amount of glucose from glomerulus but in the normal individuals it is not coming in the urine so what was happening was that at proximal convoluted tubules there were certain you know channels at SGLP1 and SGLP2 and the researchers found out that SGLP2 were responsible for about 90% of the reabsorption of the glucose which was filtered through the glomerulus and if we they thought if we are able to block these channels or then there would be increased glucose excretion in the urine but the serum concentration of glucose will reduce and so I would you know be very candid in accepting that so once these drugs were being discovered we thought that it is kind of antifysiological mechanism but once these drugs came into existence and the drugs are like cananglifogin, dapaglifogin, umpaglifogin they showed a very phenomenal outcomes in trials as well as a real world and today we are using in a day to day practice and they have translated into very good glycemic benefit, good glycemic control and it is not only the glycemic benefit it is also beyond that it has a safety and benefit with respect to the kidney disease and ethylosclerotic cardiovascular disease and in heart failure as well. So that's what has been a very promising development in the last 5 to 10 years and we have now molecules with like SGLT2 inhibitors and GLP1 analogs which are now being used even in patients who do not have diabetes just for the benefit that they have on kidneys and the heart. So that's something that the students should read more about and look at it in a very promising future that these drugs have. Now moving on to probably the most important molecule in management of diabetes which is insulin. Insulin happens to be a complex molecule because of the various formulations that exist and to understand insulin itself would probably take a podcast to explain. So I just want you to briefly tell our audience what are the various types of insulin in practice and why do you need so many different types of insulin when actually nature in human body has only one insulin with which it manages everything. Yes sir, so as you said insulin is one of the most important intervention and in practice we often see that we have to use insulin in many scenarios in diabetes and I am not talking about Taiwan diabetes where it is exclusive drug and has to be given and there is no thought beyond that because that is a scope which we would be discussing into the separate podcast but yes in the type 2 diabetes and in the other type of diabetes insulin is very important drug and in all the emergencies hyperglycemia related emergency when the patient present with the catabolic state and even though in the inpatient critical illnesses and many other situations and in the situation where the patient is not getting controlled with a usually available oral anti-diabetic drugs we have to choose insulin. So what is insulin? So normally in the body we have two patterns of insulin secretion one the same kind of insulin there is the same insulin is secreted at a basal tone which gives a basal coverage throughout the 24 hours and there are also perennial excretion of the insulin which God has made in response to the your diet intake obviously when we take a carbohydrate or any diet then it has to be neutralized and for that we have a perennial secretion and that happened three times at a beautiful graph which is available online and in all the books which our students can refer to. So basically the scientific community prompted to replicate or mimic this physiology so they did a research and then from the conventional insulin which were made from the pancreas of the poor sign and other animals it now we have graduated towards you know the graduate towards a DNA technology and now we have a designer insulin which are available. So basically fundamental is that you basically you are trying to mimic that physiology where you are trying to give a basal insulin which should have a coverage throughout the day and one which should give a cute excursion to address the perennial or food consumption. So with this need we have two types of insulin which are available one would be rapid acting which would be addressing that perennial excursion or shorter acting for that matter and one would be a basal or longer acting kind of thing. So among the shorter acting we have a regular insulin but the regular insulin had the weakness that it had a very long duration of the action which you know once the it was meant for that perennial addressing of the food consumption but you know the onset of action was also delayed you have to take it around 30 to 40 minutes prior to your meal and the duration of action also lasted about more than you know the duration of the food content so it had a propensity to cause a late post perennial hypoglycemia. So this weakness was identified and then we have a rapid acting insulin so which constitute as part your LISPRO insulin gluocene and we also have ultrafast acting you know versions of these as parts and LISPRO so they are just making you know the perennial insulin which the god has made so it can be taken immediately with the meal and it addresses you know the post meal glucose rise and then you know it has a it immediately after you know the one one and a half hours to two hours it you know goes off from the concentration and as I talk that there has to be some basal insulin so we have a basal insulin which you know can take care of the you know that base the basal tone which has to be maintained throughout the day and for which we initially had deti mir which did not have a duration for entire 24 hours has to be given twice a day then we had a glass chain which could add a short duration which also did not cover it 24 hours and now we have an insulin like degluteg which can give a coverage which can last more than 24 hours and these insulins are meant to be you know giving the basal tone can be taken you know anytime like degluteg can be taken anytime of the day so basically we are making the physiology where we are providing you know the basal tone as well as you know the perennial coverage and our audience would have understood by the now time so in if you are trying to mimic this and whenever we are trying to utilize the insulin we may have to use you know the insulin three times one is for the meals rapid acting insulin for three times once before each meal that is breakfast lunch and dinner and one we have to take a basal so that would you know come to about four injections so that was also a shortcomings and the hence whenever we have a weakness which is identified so that leads to research so scientists also you know did a research where they discovered they mixed the insulin so that a single injection can only give a perennial coverage or rapid acting kind of coverage and one can give a longer coverage so there we have a spart to mix the 70-30 we have a lis pro mix various you know 70-30 or 50-50 are available so how they were made so as part when it is you know protonated the it becomes a little longer acting and a simple rapid acting as part is mixed with the like protonated as part and vice versa with lis pro as well and they gives us a coverage of perennial and you know the kind of longer also so these kind of insulin can be used twice a day so just for a sake of convenience they are ideal insulin which can be given just before break for one injection before breakfast and before dinner and we have a better version advanced version where even a deglutek is combined with a spart and the same kind of benefit of basal and perennial in a mixed kind of thing can be utilized in then so so so broadly so these are the basically insulin and there are certain nitty gritties how do we use insulin and generally we can at times start with only basal then we can graduate towards you know the rapid acting which is called as boluses or we can choose once a mix and they are these options or we can play around in real time patients in appropriate setting so insulin is definitely the most effective drug as far as managing hyperglycemia is concerned and it has very few if any contra indications then and it's very effective in all situations so but we also know that type 2 diabetes is not a condition where you always require insulin you can always manage these patients with oral drugs as well so what are the conditions in type 2 diabetes where insulin plays a major role as a treatment. Yes sir so basically majority of patients as we have discussed would be managed by the oral drugs for the diabetes but occasionally sir we land up with a situation where we have to use to do the insulin and the most important number one I would be say when if the patient is sick that is a message which all of us should understand when the patient is sick please choose the insulin when patient present with first time with the severe hyperglycemia and if we have to give a figure according to the guidelines that comes from HDI again from 2024 if HVA once is more than 10% or blood glucose level is more than 300 milligram per deciliter please start with the insulin and the concept behind this kind of beta cell rest it gives if you use insulin initially when if the patient has a severe osmotic symptoms or catabolic state means patients having a weight loss ok you know patient is sick is having a increased appetite you know polyuria, polytipsia with weight loss in such a scenario please go ahead and use insulin till you stabilize the patient and slowly you can you know the vene of the patient towards the oral drugs and then as I told the patient who are sick who are in ICU patient who requires surgery patient like in the gestational diabetes in such patients where the insulin becomes a choice and there are hyperglycemic emergencies like we are aware about diabeticative seduces hyperglycemic hyper osmolar state even without these complications if we are hyperglycemia the insulin becomes the drug of choice in such patients and then in type 2 diabetes which are garden variety we often don't require initially with insulin but since the diabetes is progressive disease the beta cell reserves falls subsequently and once this patient progress and not not controlled by 1 or 2 or 3 drugs there is no use of adding more drugs subsequently because studies have shown that addition of drugs beyond 3 would not translate into good glycemic benefit and in those scenarios also sir we you know start with the insulin we choose insulin at least we start with the beta cell kind of insulin in those patients so fine we have actually talked about all the drugs that are available and it's one of the few conditions where you have so many options so although it's a very good thing to have too many options but it also makes it very confusing for the patient as well as doctor when you are encountered with so many options so as a person treating diabetes how do you select a drug for diabetes so if you could just give a few examples or based on the guidelines how do you manage to decide how which drug to start and how to follow yes sir this is a very very important aspect of the diabetes management in fact all the knowledge which you gain from reading textbooks or from learning you may not get you know the clear algorithm how to approach using the drugs because I mentioned earlier all these drugs are have their own advantages and disadvantages and not to forget as sir as mentioned that cost is very very important and which we should keep in mind and it is not only cost I you know take you back to our first podcast with respect to diabetes because we have our Indian population has a unique pattern of diabetes and hence we need to you know the tailor treatment or modality according to our patients and which we have already discussed so sir coming to how to choose a drug is important so first of all let me tell you that in a normal garden a variety of the patient it is always prudent to start with a metformin we start with a metformin and it has a got a phenomenal benefit it is a affordable it has a you know the weight neutral and in fact at times may be well with respect to weight so that is a drug of choice so beyond that I just want my audience to remember six things which are important while managing diabetes and that is number one is presence of chronic kidney disease number two is presence of coronary artery disease number three is present of the heart failure number four is obesity number five is consideration of the hypoglycemia and number six is a cost so this six aspects six verticals you should always remember whenever you are instituting using which drug to select from where so these things should be looked for so if I come to the obesity as we were discussing so you should choose a drug which you know give us a benefit with respect to weight and even if you are dressing the cost please try to choose a drug which does not give a additional weight gain to the patient so like I just discussed earlier so insulin is a drug or insulin scretagox which we are talking about cell phonylureas they are the drugs which can cause weight gain so we that these they would not be appropriate in whenever we are also addressing obesity and management of obesity is integral framework of management of the diabetes and in appropriate in available resources the drugs to choose is as we talked about SGLT2 inhibitors they should be there they can be chosen for weight loss but ideally would be a GLP1 analogs glucagon like peptide 1 and we were discussing earlier they are in creatine kind of molecules and they also have a glycemic benefit but also translate into a significant weight reduction and that has been and we have a you know robust scientific evidence with respect to use of these drugs and they cause weight gain by you know the delaying gastric empty they are the central level also they act you know by decreasing the appetite and many other mechanism why which they help in the weight reduction and then I told you we can also use as a LT2 inhibitors in these patients who help with respect to the weight weight loss and otherwise DPP4 inhibitors like Lipton group of the drugs they are weight neutrals and even the metformin may have some benefit with respect to weight loss so that is obesity which is most important so we are coming to coronary artery disease whenever there is a coronary artery disease if resources permit we should use a GLP1 analogs in these patients if not if or SGLT2 inhibitors because both these drugs have demonstrated the cardiac benefit in the real world life and we have a robust evidence with respect also coming to the heart failure I am not talking about only the heart failure with you know preserved reduced ejection fraction but also with a preserved ejection fraction and again we have very very robust evidence that these are beneficial in the management of the heart failure and in the chronic whenever there is a chronic kidney disease again the these both these drugs like you know the preference would be the SGLT2 inhibitors because they are trial like you know MPAR, kidney, credence all these have demonstrated they are beneficial in the kidney disease and the GLP1 receptor analogs can be chosen in them then coming to the hypoglycemia and this is very important answer we like we keep on discussing everyday is the hypoglycemia is one of the also important aspect we often you know is compromised in the various practice places and we should always remember because it often seen in the elderly who are you know having a multiple comorbidities and interaction with the drugs so sulfonylureas and the drugs which we scrape about insulin they have a propensity to cause hypoglycemia that should be kept in the mind because there is no use of you know controlling the glycemia if the patient your patient land up into the fatal or disabling hypoglycemia and the most important which message which I want to convey to audience is that our country is in the phase where we have a you know the both the world where the people can have a good affordability where we can use all these drugs but in other scenario we may have to you know the select the drugs which patient can afford and there as we were discussing the older or conventional earlier kind of older anti-diabetes would be good choice and we can play around with them to achieve our targets so cost factor is important because it was easy and I can you know tell you about various trials and outcomes but as long but all these drugs would be very costly and they may not translate into benefit to my patient in the real hope it is when I see them. So it's very important to understand each drug the benefit that it has and the setting in which we are going to use them as far as the patient his comorbidity is concerned so we must utilize these drugs for the best of their benefit without there being any contraindication and of course affordability is very important. Now also the fact that now any of these drugs can be used upfront although we always use metformin as the first line but we can always use any of these older drugs that you spoke about upfront for the benefit that they have. Depending on insulin always remains a choice thereafter once we have achieved or not able to achieve those targets or we can add further molecules and beyond like you said two or three drugs there is no great advantage and we have to resort to insulin. So management of diabetes is always based on targets and what are the targets that you are looking at when you treat a patient. So this is very important so basically what happens is if I have to tell you know what is the guidance so I would say that HV1C less than 7% fasting blood glucose 80 to 130 and your post-prandial glucose less than 180 milligram deciliter is your targets. But then this statement might not be right in practice because it is you know if my audience or my students who are hearing they can go with a rigid idea where they would apply this framework in the 40 year old or 30 year old patient with the diabetes and they would also apply this framework in the patient who is elderly living alone they have multiple comorbidities and who is around 80 years old. So what is the important message and which has been taught to us by you about a decade back also that always remember that there is an individualized or personalized management of the diabetes mellitus. So you have to you know select your targets according to what type of the patient is sitting in front of you. If the patient is young, he is educated, he is more alert about conscious about his diabetes management, he has increased life expectancy, he has no comorbidities and individual you know have you know increased motivation you can have a stringent target and where you can at times get back to even the lower than 7% can be the choice in them. And then we the contrary we have elderly patient where the life expectancy is low and you have you know a lot of comorbidities in them there is a social constraints with respect to the management. If they have a visual impairment, if they have other disability like hearing impairment in them we need to be very very less stringent we have to be liberal and at times even more than 8% 8.5% HPA1C or more liberal control would be you know more prudent to approach these patients. So basically the message is that the literature says that good you know the stringent glycemic control translate into better microvascular complication benefit but at times it may can lead to you know the disabling and fatal hypoglycemia and even it has been seen that very tight glycemic control can have adverse cardiovascular even the patient who have cardiovascular disease hypoglycemia tight glycemic and glycemic control might not be good. So it is very thin line where we have to walk and it is a personalized and individualized management which should be applied there and those are we have latest you know technologies also which we are coming and we are utilizing like time in range when we are using the continuous glucose monitor where we try to achieve 70% of time in range which is the glucose level within you know 70 to 180. So in a simple way I want to tell my audience that the amount of time the patient should be living within this target sugar glucose would be 70% and maybe you know less than 50% or 50% in the patient who are sick and having multiple comorbidities or the care amount of care is not very good with them. So I think key bird there would be individualizing therapy and so that is why even now when somebody asked me what is the treatment for this level of glucose I always tell them or ask them who is the patient because unless you know who is your patient in front of you you cannot decide targets for them and accordingly you cannot use the drug that you want to and that is where I think to a great extent treating diabetes is an art more than science although science is helping us to treat it very artistically. Now diabetes is not all about glucose management and especially type 2 diabetes where there are various other factors like the lipids or the blood pressure or excessive adhesion of platelets or inflammation which is contributing to various complications. So when you manage type 2 diabetes other than glucose what are the targets that you are looking at and what drugs would you use in these patients? So correctly brought out sir in my opiates I try to say that diabetes is not about the sugar at all and it is it can encompasses the holistic management or other aspect also. So I mean I will give you know the basically the example to audience so imagine if there is a patient who is a 40 year old and you are having a very good glycemic target of 7% and everything is fine and he comes to you with blood glucose of 100 fasting and even good control so you know what happened would you be happy? So answer to that is no because we have to see the patient in a holistic picture if that same patient is obese or is gaining weight, if that patient is not having a good blood pressure, if that patient is having a deranged lipid profile, that patient has developed a fatty liver disease and that patient is having a you know increased risk for atherosclerotic cardiovascular disease. So I think we have failed in management of the diabetes and that is not a proper management of the diabetes. So diabetes is a holistic three-dimensional look where we have to address the patient's blood pressure, we have to address his atherosclerotic cardiovascular risk, obesity and even other aspects of the social aspect also because these patients also go on to develop diabetes, distress and depression. So coming to few important things which we should keep in mind is the blood pressure. So these patients we should target the blood pressure less than 130 by 80 and the BP if we are higher has to be confirmed in two or three occasions and if it is higher then we label these patients as hypertension and in those scenarios you know ARBs, angiotensin receptor, blockers or ACE inhibitors would be a drug of choice. Then coming to the statin therapy and this is the problem which we see in our prescription in day-to-day life. So the statins are basically it is not only for you know the cholesterol or LDL components of the lipid management but it also has a various pleopropic and clot stabilizer effect where it can translate into better atherosclerotic cardiovascular risk. So it has been seen that all diabetes over 40 to 75 should be on statin, at least moderate intensity statin and the high intensity statin can be given if they have very high LDL levels are present and the patient who are less than 40 years of age in whom then also we can consider statin if they have a high risk for cardiovascular disease. So how do we you know target these statins so it has been seen that the patient should be having LDL cholesterol less than 150 milligram LDL cholesterol less than 100 and in the patient who have established cardiovascular disease his LDL should be less than 70 and his triglyceride level should be less than 150 and that then we would say that he is adequately managed and when we choose you know the moderate intensity statin we are aiming at about 30 to 40% reduction in LDL and in that scenario we use about 10 to 20 milligram of torvastatin or 5 to 10 of asrosovastatin and double the dose is called as high intensity therapy and that is used in the patient who have a high cardiovascular risk and high LDL level and there we are targeting more than 50% reduction in the basically LDL cholesterol and also with respect to aspirin so the secondary prevention means when the patient has established cardiovascular disease then there is no doubt it has to be used but yes in appropriate setting when you think your patient is you know having a high risk for the cardiovascular disease we should choose these patient to have we can you know give this patient on a ecospirin and we can aspirin so that they we can address their cardiovascular risk as well and not only this we should you know address the patients these days non-alcoholic fatty liver disease is common in we should test we should screen this patient and appropriate intervention should be given obesity we have already discussed that should be addressed and even the your psychological health and as I told patient who find the problems with diabetes management and they can manifest with diabetes distress and you know diabetes depression as well so diabetes constitute you know addressing the overall health and the primarily the targeted towards atherosclerotic cardiovascular disease chronic kidney disease fatty liver and their blood pressure and even their psycho social health as well. So I think that's very comprehensively addressed these are various other factors other than glucose that we need to target for ensuring that patients get optimum benefit lastly I would just like you to summarize on the follow-up aspects of these patients once we have started them on therapy how do you follow them up how frequently they do they need to do their glycemic control checks or other tests that are required. Yes sir that is also very important aspect because even the best started treatment may not translate into good outcomes because follow become poor and that is relevant in our practice because when the patient has to come from far off an education level if it is lower. So basically sir coming to the blood glucose level if the HPA1c is well controlled that is can be defined by HPA1c less than 7% patient can be you know test these every three months and uncontrolled basically should be you know the followed up frequently and sometimes you know very uncontrolled sugars we can test this every two weeks also HPA1c is important because it carries the cost also because unnecessarily investigation is not required. So if well controlled less than 7% should be done you should repeat 6 to 1 year. So even once a year HPA1c is good enough in uncontrolled you can do it every three months and I already mentioned that you know neuropathy annual assessment has to be done foot examination every three months has to be done test for retinopathy should be done one to two years if it is not present if it is present then you have to do two to three times in a year and the annual exam screening for nephropathy should be done by albumin creatinine ratio and other components like lipid profile and urea creatinine and even your liver function test can be done once in a year and not to forget the clinical examination taking blood pressure and you know assessing the clinical should be done every visit in these patients. So I think that's a very comprehensive assessment that is required in every patient of diabetes because whatever drugs you use the disease is a very active disease it's a progressive disease so whatever you use today and is adequate may not be adequate tomorrow. So it's very important that we continue to monitor the patient we educate the patient to monitor themselves and also come back to us more frequently if required to ensure that the targets are achieved. So I think in this podcast we have addressed the issue of drug therapy of diabetes and the follow up very comprehensively it's a it's a complex interplay of various drugs and their effects, benefits, advantages and disadvantages and their effects on the comorbidities. This is an understanding that a student can develop over years of learning and practicing clinical medicine. So the learning goes on and I think you will agree that we are still learning every day that we see our patients and that's why that's what I expect from our students also and they should continue to learn while they teach and practice medicine. So with this we come to the end of this edition of podcast and our discussion on the topic of type 2 diabetes. I'm sure the students have learned a lot but they would have to revise, come back to us if they have any doubts and they seek clarification and we'll be very happy to answer their questions and also as always we expect them to give us feedback and any need for improvement in this that we would be very happy to address. So thank you Sandeep for sparing your time and I hope that our discussion in this topic further would be on type 1 diabetes which we will address in the next few weeks. Thank you sir.