Robert Busch, MD: Reaction to EMPEROR-Reduced Topline Results

An endocrinologist with The Endocrine Group discusses his reaction to the topline results of the EMPEROR-REDUCED trial scheduled to be presented at ESC 2020

And a practicing endocrinologist and someone who has a special interest in cardiometabolic health as a whole we saw this sort of quote unquote class effect from sglt2s first displayed in dappa hf where it showed benefit for heifer often patients with and without diabetes what does it mean to you now as an endocrinologist that this is almost all but confirmed that

This is part of a class effect that we’re seeing this cardiovascular benefit from epilephasa now it’s great for us as prescribers and great for our patients and what’ll be interesting is when the cardiologists come on board as you know most cardiologists you know they they look at the data they like the data but they don’t prescribe the drug and still sglt2s are

Vastly underprescribed so i think even from when emperoreg showed less heart failure hospitalization not in this population and then it was shown in the other uh studies uh canvas showed that as well then certainly credence got the indication in the renal patient and dapper uh declare showed it sort of as almost primary prevention diabetes with risk factors but

There was that sub study of declare if you looked at the low ejection fraction patients they did dramatically well that was sort of the appetizer to dapper hf and now you have this so and then even with vertices lack of of uh no mace but benefit for heart failure obviously this is a class effect of this class are they different do some do better than others well

You know they have different populations and stuff um the background medication makes a difference how well treated they are do you have additional benefit beyond their background therapy what will be interesting to see in this study because the inclusion criteria is pretty similar the gfr went down lower the gfr went down to 20 in emperor heart failure and 30

In uh in uh dapa uh hefref but um what is the background meds like there are a lot of beneficial background meds for heart failure was there the same amount of rass blocker or the or the uh arnie’s whether it was is more intresto in one verse to the other which makes it a more difficult bar to improve upon it’s a higher bar if you have a lot of better good stuff

On board for the patient to prevent heart failure and then you prevent heart failure on top of that so that’ll be interesting uh one you know class effect yes all great for heart failure two is there a difference uh can you still do better and better despite what the background therapy is so that’ll be important too now let me ask you as we learn more about the

Cv benefits of this class do you think that there will come a point where it sort of becomes a decision for the cardiologist whether to describe sglt2s in their patients that are diabetics or is this going to remain sort of in the endocrinologist’s wheelhouse so who’s treating diabetes primary care and endos and those i think are more aggressive with sglt2s but

Certainly there are excellent primary care docs who do the exact same thing that we do and use the same you know glp sglt2 and you know like we do it versus a more traditional either met salt for medtepp4 basal insulin versus sglt2 and glp1 so will cardiologists do it well i think heart failure has always been their domain so um will they do it and bite the bullet

And say okay look you know i’ll give the primary care one shot or i’ll put it my note and if the patient comes back to me i’m doing it the next time but why wait you know you can avoid that heart failure hospitalization while they’re waiting so you know this class is what you’re discussing with the patient in terms of of uh you know if they’re on hypoglycemia

Drugs like assault for insulin i think the cardiologist will have to be comfortable with tapering that or let the primary care doc know i’m starting this medication for heart failure i know they’re on other diabetes drugs that can potentially cause hypoglycemia like insulin itself but if they’re just on metformin or glp1 or dpp4 you know they have to know and be

Reassured you’re not going to get hypoglycemic so don’t worry about that and the yeast infection thing yeah cardiologists may have to ask patients are you an uncircumcised man or do you get a lot of yeast infections or if you’re a woman and they don’t usually ask that question of their heart failure patients so but i think you know they’ll come around when they

See the impressive data with this as add on to the other standard of drugs that they use it would be like saying okay i’m a cardiologist i’m using a statin but i’m not going to use zetio i’m not going to use a pcsk9 that’s someone else’s problem because it’s an injectable drug or whatever you know they do if you’re a lipidologist you do lipids and you don’t have

To be a cardiologist to do lipids just like you don’t have to be an endocrinologist or diabetologist to do heart failure therapy i don’t expect them to do to manage all the diabetes because you know they have enough other stuff to do but i bet some of them do that either the minority do that and certainly the minority are prescribing this class of drug for their

Patients but i think they’ll come around eventually so we’ll see depends how much hand-holding they need and reassurance that they’re doing no harm thank you for that and now as we move forward and we learn more about these drugs and sort of the benefits that they give it seems a lot of people are still a little bit reluctant um it seems a lot of people still

Favor glp ones for hba1c control and weight loss what type of risk factors would you have to see in a patient beyond just being a diabetic for you to initiate therapy with an sglt2 hoping to sort of see that benefit and reduce heart failure or improve renal function so what kind of risk well first of all the good diabetes drugs remember that’s why they first

Came out you know not every diabetes drug do you not get hypoglycemia lose weight and lower blood pressure so it’s sort of they call it diabetes trifecta to do that when they first came out and they compared very favorably with dpp4s in terms of a1c drops dpp4s were the market-leading branded drugs after met self but then you’ve had emperor egg and then you had

The renal the emperor egg and the other cardiovascular trials with sglt2s then you had credence and then we’ll have the dapa ckd and eventually have empa kidney and now we have two you know mega heart failure trials so i i think it’s enough to say okay i’m giving this drug early on in diabetes will they ever supplant metformin which doesn’t have this kind of

Cardiac benefit or heart failure benefit or renal benefit i don’t know i mean maybe because of course metformin will always come first but metformin has you know substantial side effects we know that metformin just had that pull with the metformin ers where it was very distressing for patients to call up to get a call from their pharmacy that your drug may cause

Cancer call your primary care doctor see what they want to put you on so you know i think the more of that stuff with metformin and the more cardiovascular benefits with this class where it’s not only am i stroke and death but heart failure and renal protection and i we’ve talked about this once before if i told my chief of endocrine you had a drug that lowered

A1c lowered weight lowered blood pressure prevents end-stage renal disease or lowers the slope to that treats and prevents heart failure hospitalization and lowers mi stroke death and death that’s a pretty good drug what a yeah like that so i think you’re going to see a lot more use of it it’s vastly underused even though the drug’s been out several years and

Cost usually isn’t an obstacle with commercial insurance because these drugs have very good copay cards so most of them with commercial insurance are free to the patient so that’s a big deal you know whereas it’s a very generous copay card for commercial insurance and even medicare and the other government plans tend to cover this class of drug may not may not

Be the one you want to use but at least you can get it sglt too and then just lastly i know you hit it on a little bit in your answer there well the latter half of your answer there despite some really strong data there seems to be a bit of hesitancy still on behalf of some endocrinologist or some primary care specialist to prescribe these drugs i’ve seen some

Figures suggest that it takes five years after a drug’s approval for people to really start prescribing it the way they should what do you think are some of the barriers that still exist because from my perspective all the data seems really great it seems like a no-brainer that you should be prescribing sglt sglt2 inhibitors to your patients but what are the real

World barriers to the clinical application of this data and these drugs so still discomfort with the mechanism many of us grew up on sugar in the urine is bad now we’re leveraging the kidney to by blocking you know the proximal tubule sglt where the transport system is to leverage the kidney to urinate out sugar so some are still uncomfortable with that mechanism

The yeast infections what if you get burnt and you choose the wrong patients in your first five patients get a yeast infection you’re going to be a little slow to prescribe it on the sixth patient you know i i personally when i used an ace inhibitor early on when i used capital adaptation with angioedema well imagine if i never used an ace inhibitor after that

So you know that was one in a hundred thousand but here yeast infections are not uncommon and yeah you could define you know you could um leverage your risk by talking to the patient when was your last yeast infection 20 years ago that’s different than someone when was your last yeast infection oh i have one now and i’ve had five in the last year and i’m on an

Antibiotic that’s a different kind of patient who’s at risk for the yeast infection some are painfully fearful who haven’t prescribed the drug of urosepsis because it’s in the package insert well utis are not uncommon if you ignore a lower uti and treat it as a yeast infection you’re going to get an upper uti because diflucan doesn’t work to treat a a uti so i

Think if they get burnt by side effects it takes some time to discuss this with the patient the typical verbiage is uh you know this drug will make you urinate out more sugar salt and water it will drop your blood pressure if your pressure’s too low you might get hypotense you may want to cut down the thiazide diuretic that they’re on you’re not in a heart a

Heart failure patient they’re on uh you know loop diuretics but you might want to back off a little bit on that loop diuretic because this has a glucoretic effect to it and that’s not going to negate the heart failure benefit effect that has not just a diuretic effect is as you know many other benefits the sympathetic tone goes down and other things like that

Um but they’re talking to the patient you give it to a man with bph who’s urinating every hour what are you going to say now you can urinate every half hour so you have to choose the right patient give the right counseling and you know and and have benefit with the first couple of patients you prescribed it if you’ve never prescribed it before not that you get

Burnt by side effects that the man with bph calls you back i’m peeing too much or i’m thirsty all the time or i’m passing out because their pressure was 100 to start with and you didn’t cut down the thiazide or they’re on a sulfur insulin and the drug worked and they got hypoglycemic so the counseling to a patient that takes a couple of minutes and you know in

A follow-up office visit those couple of minutes would have been spent doing something else so it’s a decision if you’re going to start this is not just here’s your script goodbye see you the other thing is the drug works very quickly to have its benefit you know the the separation of the curves happened early i i think it happens within 20 or 30 days in in dapa

Hf it happened very early on some of my colleagues kid around and say that it happens as soon as you e-scribe the medicine the patient has benefit but i do think they have to put it in their mouth first at least take it a couple of weeks but most patients on the drug want to stay on it and interestingly if you had a woman with a yeast infection or a history uti

After it’s treated they want to go back on the drug you know they know the drug caused some weight loss the drug has these other benefits so they want to stay on the drug the drug made up lower their a1c better than previous drugs so i think the time it might take to discuss with the patient is a little more than here’s your dpp-4 and move on to something else

But of course dp people you get what you pay for dpp fours lower sugar don’t get enough hypoglycemia no weight loss no blood pressure lowering and none of these cardiovascular benefits are renal benefits so it’s a long answer to your short question uh sometimes the long answer is needed it’s definitely a bit of a troubling question when you see this great data

And wonder why people aren’t prescribing it and just lastly before i let you go what exactly are you looking for when you go and watch the emperor reduced presentation uh at the end of next month in august what are you looking for from that data as an endocrinologist okay you even know the timetable of this that’s it’ll be right at the european uh meetings that

Will be discussed so what am i looking for what were the background meds that they want how does it compare is it different than the background meds in dapa hf where they are with a better managed patients where they’re more you know more rasp blockers more rnas more of the other standard of care cardiovascular drugs but modernized regimen what was different

There we know that some from the dapa presentation i think you interviewed um silvio anzuki about the prevention of diabetes when that came out at ada i watched that see your your style which is very good but anyway they may look for time to development of diabetes how you know that’s different you know of course you’re going to get less diabetes you’re using a

Drug that makes you clear sugar in the urine but time to development did that go down and the average time in the placebo group and these are in the patients who did not have diabetes so not only prevention of diabetes but what was the separation of those curves how quick did that happen so things like that i’d look for that obviously that you know what was the

Overall um heart failure hospitalization and the the combined endpoint and then how did each one individually do so i think the background therapies would be different the uh different percentages of of the um cardiovascular death or heart failure hospitalization how did that go out as the primary endpoint and then a lot of the secondary endpoints they may have

Some different things the renal benefits of the drug here the gfr went down to 20. how did those patients do how the gfr 20 to 30 patients do because that wasn’t studied in in dapa hf because i think the cutoff was 30 there so the trials differed enough that you can get some additional data versus saying okay big whoop i know this already from before what are

You teaching me new you know so they extended the gfr to 20 there were different background meds in the in the uh study as well you know maybe was there a lot of glp use in this versus before it was a later study maybe there’s more glp use in the background that so i don’t i don’t know you know and i’m sure there’ll be some other things they point out

Transcribed from video
Robert Busch, MD: Reaction to EMPEROR-Reduced Topline Results By Practical Cardiology