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Expert speaks series |2| Dr. Neeta Despande talks about benefits of Dapagliflozin in CKD patients.

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Dapagliflozin belongs to the class of drugs known as Oral antidiabetics or antihyperglycemic agents.

So greetings everyone my name is dr supredic bhattacharya and today it’s an absolute pride and pleasure to have with us dr nita deshpande dr nita mdf rcp edinburgh and uh post graduation endo from london is bp obesity certified from usa and he’s the senior consultant dermatologist and bariatric physician she is also the director of belgaud diabetes center

With watch children’s diabetes center she’s a professor and head of the department of medicine mm dental college bill cow and also associate professor of medicine usm kelly international medical program she has several presentations on obesity and diabetes in national and international meetings she has done publications in peer review journals and textbooks

She’s been the past chairman of karnataka rssdi principal investigator for several clinical trials krss d.i oration for 2016. she received the rssdi fellowship in 2016 and frcp edinburgh december 2016. she has been the coordinator of the consensus group rssdiesi clinical practice recommendations for type 2 diabetes 2020 and she is a close personal friend as

Well so it’s once again uh absolute privilege to introduce to you to dr nita thank deshwande so much dr bhattacharya and today i i should thank the organizers also for giving me this opportunity to speak about this molecule and this class of drugs in particular which is the rage now and i would say i wouldn’t be wrong if i said that it’s the molecule of the

Century actually speaking and i shall launch into certain aspects of it especially about the heart failure aspect which is being talked about now a lot with respect to diabetes uh and otherwise also so here we’re going to talk about diabetes heart failure and dipagliflosing well just to give you an introduction of the connection between heart failure and

Type 2 diabetes let’s first look at the burden of heart failure in type 2 diabetes patients we all know that diabetes increases the risk of heart failure twice in men twofold but five-fold in women and the term diabetic cardiomyopathy which is basically heart failure was coined 40 years ago so in general we know now that patients with diabetes mellitus are

At greater risk of developing heart failure than their counterparts without diabetes and the risk is at least twice those of non-diabetic individuals which is considerable if you had to look at why this is so and what the pathophysiology of heart failure and diabetes is to put it in a nutshell we all know that pathophysiologically in diabetes what you have

Is hyperglycemia insulin resistance and hyperinsulinemia and this triad which is there is responsible for several metabolic problems for example you have inflammation dyslipidemia and endothelial dysfunction because of this triad of metabolic abnormalities which of course predisposes to coronary artery disease and that can lead to ischemic cardiomyopathy and

This can lead in turn to heart failure also there are other mechanisms by which diabetes can predispose to heart failure and that is cardiomyocyte hypertrophy or lb hypertrophy which can again lead to diabetic cardiomyopathy leading to heart failure also you can have the renin-angiotensin system to get activated which in turn leads to this cascade also you have

Autonomic dysfunction there could be disordered calcium handling formation of advanced glycation end products and all of these together contribute towards diabetic cardiomyopathy leading to heart failure therefore this triad of hyperglycemia insulin resistance and hyperinsulinemia that often accompanies diabetes triggers a cascade of deleterious effects that

Contribute to the development of heart failure in diabetes therefore not surprisingly the risk of developing heart failure because of all these events is at least twice that of non-diabetic counterparts and then you have so many therapies nowadays and nowadays apart from reducing the blood sugar you also talk of cleotropic effects you would always want an

Anti-diabetic agent to do more than just reducing the blood sugars and that is why you have a plethora of agents today which can do that and different uh anti-diabetic drugs act through different pathways and give you different effects so you have the bygonites the sulfonylureas the tcds etc you have the whole list of them that are helpful in diabetes mellitus

And they are going to act through various mechanisms such as the liver the pancreas the kidneys adipose tissue the skeletal muscle etc and with all of this they have variable effects on the propensity to cause heart failure as well so these are the different ways in which you could modulate this particular function by giving an altered myocardial substrate

Metabolism mitochondrial bioenergetics playing around with the oxidative stress and the lipotoxicity reducing inflammation endothelial endoplasmic reticulum stress etc so these are all the different areas in which the different drugs can act and bring about pleuotropic effects in a bid to reduce the heart failure problem in type 2 diabetes now coming to

The other end of the spectrum and that is the hb a1c we all know that the hemoglobin a1c is the parameter that we use to assess the glycemic control of a person most clinical trials or rather almost all the clinical trials up until now use this as the goal post and hba1c is important for us and all our guidelines tell us what the hb a1c should be like now

Uh in the latest ada and easd guidelines and in many of the other guidelines also in the recent past rather than having a fixed goal post the goal post changes based on several parameters and there could be patient factors there could be cost factors and many more for example if a person is expected to live long and has got stage a b or c heart failure no

Serious comorbidities no serious diabetes complications and that person can have a 6.5 percent you can have a target of 6.5 percent on the other hand when you have somebody who has a limited life expectancy and has got organ damage and so many other comorbidities in such patients your goal post is different and it could be as high as eight point five percent

So a patient’s clinical and functional status self management capacity the social support the hypoglycemia risks the costs etc all of these are going to matter when you are going to decide what the target a1c should be for a particular patient now comes the role of dapagliflozin in patients with heart failure you have the famous zapa hf study and you will have

Insights from that study into this this was a seminal study in which you had more than 4500 patients with an nyha class 2 3 or 4 heart failure and an ejection fraction of less than 40 and you can see here that there is a remarkable risk reduction in fact there is a 26 relative risk reduction and a 4.9 absolute risk reduction which is very very good this is

The hazards ratio and confidence interval which is so very reassuring and you can see that right from the beginning there is a separation of the lines and all across this is the hazards ratio that you have and this study has very elegantly demonstrated that dipagliflozin demonstrates a lower risk of worsening heart failure or death from cv causes and better

Symptom scores irrespective of diabetes status now this is a very important thing for us to understand that this particular study had patients who did not have diabetes so this drug which was originally meant for as an anti-diabetic agent is now studied in the dapa hf trial where they had a population of heart failure patients that did not have diabetes and

Even in them this same benefit was seen and that is why it is said that the relative risk reduction with this drug for heart failure is irrespective of the glycemic status which is very very important and one of the important outcomes from this study so the key messages from this presentation would be that we know that women with diabetes are at greater risk

Of developing heart failure than men hyperglycemia triggers mechanisms of heart failure in diabetes patients i’ve already shown you the mechanisms with which by which this can happen glucose lowering therapies showing effects beyond glycemic control and modulating heart failure outcomes should be preferred in heart failure patients with diabetes mellitus

Also the a1c goals should be individualized in patients with heart failure and diabetes and regardless of the prevalence or absence of diabetes patients with heart failure and a decreased ejection fraction who received dapagliflozin have a lesser chance of worsening heart failure or death from cardiovascular causes so all in all this is a drug that has been

Studied very well and it has been shown to reduce the risk of heart failure which is very prevalent in diabetes individuals and it has got the cleotropic effects of reducing glycemia or reducing the blood sugars as well as reducing the risk of worsening heart failure thank you thank you so much dr this monday for your uh insights into this subject and thank

You for taking out your valuable time and being with us i’m sure all of us are going to go back wiser and use this knowledge into our clinical practice uh and just as a quick reminder that uh this program has been made possible in partnership with koi equila and watch out the space for more such enlightening and engaging videos so thank you once again for

Your time thank you so much thank you you

Transcribed from video
Expert speaks series |2| Dr. Neeta Despande talks about benefits of Dapagliflozin in CKD patients. By Koye Equila