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Highlight on Dapagliflozin in Patients with Chronic Kidney Amr El-Husseini,24 Sep 2020

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Highlight on Dapagliflozin in Patients with Chronic Kidney Disease. prof. Amr El-Husseini, MD, FACP, FASN

Hi this is amrit hosseini and i’m going to talk to you all today about an interesting study that was published today in the new england journal of medicine about use of sglt2 inhibitors that deva uh glyphosate ambitions with cqd as we know that the sglt2 inhibitors has showed significant benefit with efficacy and the safety profile in diabetic patients and also

In vision towards congestive heart failure uh two weeks ago there was a very nice new engine journal of medicine uh trial published uh called also dabba heart failure and the truth that the dabba was you know significantly able to reduce the primary and secondary composite endpoints and um patients with congestive heart failure with and without diabetes also this

Study is very interesting the one that was published today in new england journal of medicine because also it showed as a safety and efficacy of use of daba and ambition was ckd even if they are not diabetic this study is funded by astrazeneca i just need to say that i don’t get any uh fund or money from um astrazeneca or other pharmaceutical companies i’m part of

Several randomized critical trial multicenter trial but none of them are related to diabetes or to the pharmaceutical agents of using uh you know the sglp ii inhibitor so this is the study that was published today and as you see here the date is 24 of september 2020 and they used a very good number of visions more than 4000 patients all of them had chronic kidney

Disease prestige 2 3 and four with gfr uh ranging between 25 to 75 um you know per minute beer a 1.73 meter squared surface area and all of them they have protein area ranging from 200 to 5000 so some of the patients actually have a nephrotic range of protein area the primary outcome was a composite of sustained decline of egfr at least 50 percent reduction of

Gfr or in the stage kidney disease or death from renal or cardiovascular causes here is the study design so the inclusion criteria all were adults above 18 years of age with gfr between 35 to 75 and protonoria as we discussed and they have a stable kidney function on a’s or arvs for at least four weeks the exclusion criteria they excluded for some reason or type 1

Diabetics i don’t know exactly why and they also executed visions with polycystic disease lupus nephritis unconstituted nephritis and inhibition who are getting immune subreserve medication in the last six months prior to that study they uh pre-screened the visions for two weeks then they ran them the vision either to the daba ten milligram once daily or to the

Placebo so it was double blinded by cebu controlled the study and they followed them up and actually the study was terminated early because of the efficacy or and the safety of the deba and the ckd visions it is an intention to treat study so they calculated the power of the study to attain 90 percent power to detect 22 reduction and the primary composite into

Buoyancy need to have at least 681 events here is the demographic and the clinical characteristics of the participants the ages are around 61 in both groups and the placebo uh controlled group and the dhaba group uh the majority were men and uh the res the majority were white um also majority were obese with the bmi around 29. smokers just a small percentage of

The patient uh had smoking history blood pressure was well controlled and most of uh patients in this study and the egfr the mean gfr was 43 in both group and here you can see the distribution of the gfr among the two groups so very important to mention that they have about 14 percent of their participants with egypt are less than 30. this is the first study

To my knowledge that they use the sglt2 inhibitors with gfr less than 30. and here is other parameters some inhibition with nephrotic range of protonauria they have about 10 percent of vision visions with uh more than one gram of protein about 50 percent actually had more than one gram of protein so the majority have a significant degree of proteinuria a very

Important diabetics uh only 67 percent so two-thirds of the patients had diabetes one-third you know as they are not diabetic you remember that more than uh four thousand participants so if one third of those participants are non-diabetic on division with ckd for other reasons this means that they have more than thousand uh cqd non-diabetic visions in this study

Cardiovascular disease about one-third of participant had the history of cardiovascular disease ten percent had air conditioned heart failure and majority of the patient were receiving either uh ace or arvs mainly arvs here is a fascinating result you can see the primary composite outcome which include 50 at least 50 percent reduction of gfr or need for dialysis

Or a death because of renal or cardiovascular pose was significantly lower in the daba group the renal specific outcome was significantly lower also the death because of cardiovascular reason or any cause of death was significantly lower in the deva treated group and here is most important subgroup analysis and i’m more interesting here uh comparing diabetic

To non-diabetic i thought in the beginning diabetics will have more benefit but actually you see non-diabetic the hazard ratio for uh primary endpoint and non-diabetic and ckd vision without diabetes very significant 50 percent wow that’s that’s very good to know so it seemed that we now have an evidence that we can use the sglt2 inhibitors not only for diabetics

But also for cqd visions without history of debits of interest also the kidney function patients with gif are less than 45 they have relatively decreased efficacy so i think it’s uh important to note that it might be a good idea to use these agents early in the cpd rather than lead the degree of proteinuria for patients who had um you know more than one gram

Of protein leakage of urine the response was little bit less and the patient who had the um you know the systolic blood pressure was less than 130 th they have very good um impact so it seemed that we need to use it maybe earlier in ckd with less protein area and with better control of blood pressure i think these are the subgroup of vision who can get the

Most benefits also for interest here is the black population the hazard ratio for the black population seven you know 67 percent reduction of the primary endpoint and black population here is the gfr so for interest you know for the whole entire period of the study so as you see here in the deva group there was uh initial deb of the gfr bro you know possibly

Because of the decrease of the grammar filtration rate because of the decrease of intercongrature and tension but this effect on the long term you see that the kidney function was much better in the deva group compared to the placebo group so here is the summary of the primary endpoint as you can see the primary component and points that include the 50 percent

Reduction of gfr or indistinguishability disease or death because of cardiovascular or renal uh codes was significantly lower you see here 39 reduction and here’s a confidence interval it’s uh you know the range is very narrow this means that it’s very precise and as you see here’s in the state kidney disease the gf are more than 50 percent reductions all

Significantly lower in the daba treated group here is a secondary endpoint also here is you see a significant difference between the patient who received daba compared to the bracebo group so lower risk of kidney failure and all cause mortality so it’s very effective what about safety here is a comparison between the safety profile between the two groups so that

This continuation for any reason or for uh adverse events were very similar and also the adverse if you know events in general in both group world very similar you remember uh you know 10 years ago when we started to uh hear about the sglt2 inhibitor there was a concern about ambition i think this concern is vanishing now more and more study showing that it

Doesn’t increase the incidence of the peripheral vascular disease or the ambition zero ketoacidosis fracture rate is little bit higher i would i would be interested to study that and see what is the effect of the hglt2 inhibitors on the bone health arena related adverse outcome was very similar hypoglycemia was actually much less in the daba group and volume

Depletion was relatively higher so i think we need to ask the patient and discuss with the vision that because of the glucosauria and increased diuresis the vision has to drink enough amount of fluids so to conclude here it looks like the daba and the sglt2 inhibitors we can start to use them and seek divisions without history of diabetes the underlying mechanism

Is not completely understood but however there is many uh you know proposals that the benefit of this agent is not only uh depends on the glucose lowering uh effect but also because of the net ureases you remember this is not only working on uh increasing the glucose execution in the urine but also the salt execution so this agent has matures effect and actually

This is one of the major reason that we use it now in vision was congestive heart failure and also because it caused glucose induced osmotic diuresis so it improved the serum sodium it improved the volume and this is actually the concern that the vision might have some degree of hypovolemia so we have to be careful when it comes to fluid management of visions on

Sgl2 inhibitors um but it reduced the intergovernmental pressure so initially the same like ace or arb initially you see that serum creatine might go up up to 10 20 maximum 30 percent increase of serum creatine is acceptable but if the serum grate is more than 30 percent or the gfr is less than 30 percent compared to the baseline this is a concern but as you see

Safety and efficacy based on this study and other study you know every couple months now we are having more and more studies um just confirming and assuring us that the use of the sglt2 inhibitors and diabetics and now in non-diabetic visions of cpd and vision dose contrast heart failure is safe and effective i think the question now when we need to use that for

What vision and is it better to use it early or late what degree of function what patient population i think um starting to use this agent and getting ourself familiarized with this agent and their side effects and safety profile is going to tell us more and more about this medication i really thank you for listening and if you have any question please feel free

To contact me my email address is armor dot at and thank you for your attention

Transcribed from video
Highlight on Dapagliflozin in Patients with Chronic Kidney Amr El-Husseini,24 Sep 2020 By Academy of Kidney Diseases and Transplantation