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#EASD2022 Discussion on the issue of an Insulin free type 2 diabetes treatment

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EASDtv hostess Vivienne Parry speaks to debate participants Bruce Wolffenbuttel and Apostolos Tsapas together with session chair Leszek Czupryniak.

Every year on the easd program we have a couple of debates and they are always fiercely contested contests of will and passion and the particular debate that we have at the moment to talk to you about is incident free type 2 diabetes is coming but the other side says it’s nonsense so let me introduce you to the protagonists in this debate plus their long-suffering

Chair so first of all arguing that actually it’s nonsense we have bruce wolfenbrattle from the university of bronigan and then obviously on an equal footing at the moment we have apostolus satas from aristotle university in thessaloniki and the chair the long-suffering chair the one who must make the wisdom of solomon and come down between them is leshach tubrinak

Head of the department of diabetology at the university of warsaw and a firm easd favorite i might say so who is going to go first bruce i think you should because you say that this is all nonsense there will be no insulin-free type 2 diabetes treatment yeah that’s correct um i’m afraid that well type 2 diabetes is a combination of people having insulin resistance

And uh poor insulin secretion by the pancreas and when people get diabetes the beta cell function already has diminished by 50 and it goes worse over time so if you live long enough you will go to insulin now we know that there are subtypes of people with type 2 diabetes and there’s a fraction of people who’s about 25 percent who are characterized by being insulin

Deficients shoulder only logical treatment for them is insulin replacement therapy only if you’re obese you may postpone insulin treatments by losing weights and we have new medication that can do the job but in the ends after 15 to 20 years of type 2 diabetes people will need insulin replacement therapy as a logical consequence of the natural history of their

Disease so bruce is saying insulin is inevitable what do you think yeah indeed i mean uh insulin is a one of the major drugs that we’re using for treatment of type 2 diabetes but it has very significant drawbacks so use of insulin is associated with a significant body weight gain and if you compare that to novel agents that are these days available we know that

Glp-1 receptor agonists for example they reduce body weight by a significant amount of kilograms and if you think for example also of hypoglycemia we know that insulin is associated with a significant incidence of hypoglycemia which is quite important because it’s associated with increased mortality and on the other hand one might argue that people that insulin

Reduces hbo and c much more than the novel options which is not the case because we know that glp-1 receptor agonists can reduce it to be honestly much lower than insulin and if in fact this has been shown to be durable in the long term in a series of trials and post-trial observations where we see that people who are on other pharmaceutical therapy rather than

Insulin we they do lower hb and c for longer and much more efficiently compared to people who are using insulin we are living in a universe which is outcome centered we’re not any longer in an hb on scenic glucocentric universe so i think at the end of the day we have also to think of the effects of treatment on other non-glycemic outcomes like cardiovascular

Mortality or chronic kidney disease so we know that novel agents have a fantastic effect on these outcomes and i think it’s important to think of these outcomes as well and at the end of the day we know that just around the corner the novel therapies that are coming they have been tested in patients with type 1 diabetes bruce mentioned for example mentioned the

Problem of insulin deficiency but we know for example that eyelid transplantation is a very efficient treatment in type 1 diabetes and we know for example that there are stem cell derived eyelids that are now being tested in patients with type 1 diabetes which combined with crystal technology can offer viable option in patients we hope that this will be available

For type 2 diabetes in the future in the meantime we know that other options like bariatric surgery like metabolic endoscopy they are viable they are associated with a reduction in hb and c and body weight and at the end of the day which i think is also important from a societal perspective they are cost effective when compared with insulin treatment now let’s

Check if i can summarize this argument so far apostolic seems to be saying that actually insulin has had its day and if you’re preventing people getting diabetes then that’s the way to go and there are all these other new technologies coming along whereas bruce is saying that actually for at least a quarter of your diabetes patients they’re going to become insulin

Deficient and you’re going to get there anyway where do you fit in this argument well the aim of making this debate is to draw people’s attention that actually we are seeing a major shift in the treatment algorithm and insulin in which we love we are lovings we love using it in patience and and basically swing treatment is something which defines a diabetologist

One of the definitions of diabetologists this is a physician who uses instinct on daily basis and is not afraid of using it as a drug so on one hand we love it but on the other hand with the arrival of all new technologies clearly there will be a change will be and i guess we all agree we’ll be starting insulin type 2 diabetes later because the new drugs may delay

It and also what we see from the studies that both sglt2 inhibitors and glp receptor are agonists they are able to decrease the industry requirement by half so perhaps if we use these new drugs more or at higher doses or earlier here we might totally delay insulin treatment but of course we are also undergoing the change in understanding what type 2 diabetes is

And there will be new subtypes more officially arriving in coming years i believe and yeah sure there will be people like bruce madison who will need history rather sooner than later but perhaps this is not the type to diabetes we understand as we understand it today we really associate with obesity with insulin resistance and beta cell dysfunction as a somehow

The secondary thing to to beat us being unable to compensate those insulin resistance but clearly there is a subgroup of people who are different and they will take insulin whatever happens but perhaps they are not really type 2 maybe there is something totally new type we learn but we are undergoing the change and i guess we all agree and i sometimes say just to

Make the argument more provocative that if any company tried to register in swing today for a type 2 diabetes treatment they would have hell of a lot of problems because high pose increasing body weight and no effect around cardiovascular mortality so probably it might not even be licensed to be used in type 2. on the other hand indeed some people do need it we also

Live longer we also live longer the equation here that we absolutely must not forget is that people who live with diabetes for them they would really rather not take insulin they would really rather not be injecting every day so they perhaps might wish for an insulin free future yeah well we all agreed at an agent’s free future would be ideal but it’s it’s science

Fiction it’s not reality and it has to do with several things one is that islam is often used too late so if people are already in poorer control already have complications for instance insulin early in the disease can be used sometimes by doctors i have to admit as a threat if you don’t adhere to your diet you will get to insulin so people are people with diabetes

Are fearing insulin and often they have a neighbor or a family a relative who had consequences of their diabetes during insulin treatment but not caused by insulin treatment that’s one thing on the other thing my opponent gives a couple of examples of the future but island transplantation is not realistic for everyone’s type one diabetes at the moment let’s say

People with type 2 diabetes but i think we agree that there are medication that can help especially the 75 percent who are not purely insulin deficient but resistance to overcome insulin resistance to reduce body weights now israel is not very difficult but we can make it as difficult as it is and of course insulin treatment may cause hypoglycemia and the reason

That it can cause hypoglycemia is how we are using it isn’t it used on the the wrong place you’re injecting it by a subcutaneous administration it not goes through the liver like native insulin is doing and you can mimic or you can minimize the risk of hypoglycemia by multiple daily injections by frequent monitoring blood glucose which is not very popular for people

With diabetes but now with new devices like continuous glucose monitoring instant therapy can be administered very safely both in people with type 1 and in people with type 2 diabetes but let me repeat again at least a quarter needs insulin within the first five years and even if you’re obese and you have 25 years of type 2 diabetes your pancreas will be exhausted

So unless my opponent has real good pancreatic pacemaker insulin replacement is physiological replacement and maintains normal glycemia in people so he seems to be making a killer argument here how would you respond to that i mean presumably you could stratify people much much earlier you know do mass screening and that would get you to perhaps your insulin-free

Future yeah i i mean i i do see bruce’s arguments and his one must admit that in in an idealistic world where i mean everyone would be using cgm and insulin would be used under ideal conditions indeed it would be a viable option but that’s never going to happen but that’s never going to happen exactly so results both from rcts which have in fact limited external

Validity but are there with the highest internal validity as well as from observational studies which is a real world they underline the fact that insulin use no matter what regimen you are using no matter how you use that is associated with body weight gain with hypoglycemia i know that in an arguments in the debates i have full class can be presented you know

As full or empty depending on the perspective but being in stockholm i have to remind you that dr banting when received the nobel prize for the discovery of insulin he underlined that fact the fact that insulin should not be regarded as a cure but rather as a treatment i think almost 100 years after that we have to be arguing for an insulin free treatment of time

To diabetes and of course you can’t argue with that so let’s check does sum up for us why people should come to this debate because it seems to me perhaps actually more finely balanced than than you might suppose well the people should come to our debate just to have full view full perspective on the dilemmas we are facing today having our cities result on one hand

With new medications and hundred years of history of insulin users on the other hand and we have as the apostolus as both the my colleagues and friends said we have a very strong ally in discussing this issue who are the patients i’ve just met one or two patients who really asks for insulin having type 2 diabetes most of them are really afraid of for the reasons

Bruce so elegantly listed so it is still an important issue becoming more controversial with the arrival of new technology is not just drugs but also cgms so if anyone feels confused and thinks okay forget he’s been type 2 or no no you mustn’t forget it because it’s the foundation of every diabetes treatment let them come to the debate and see all the sides of

The coin and then think of yourself or yourself or your patience thank you so much all three of you and do go and have a listen to that debate because i think that you’ll find it very stimulating and as it says it gets more controversial by the year

Transcribed from video
#EASD2022 Discussion on the issue of an Insulin free type 2 diabetes treatment By European Association for the Study of Diabetes