Thread by @ckd_ce

1a) Welcome to one of our favorite events on the @academiccme #accredited #tweetorial feeds: a takeover of our programming from @GoggleDocs! The focus of this tweetorial is data from #ADA2022 on #SGLT2i beyond cardiac disease. Our expert author is @GoggleDocs' @drpatrickholmes.

1b) Check out our other #ADA2022 recap #tweetorial by new @GoggleDocs family member @Ines_VFonseca who focused on the cardiac data presented: ckd-ce.com/dkd13_ada22a/

2) This program is #accredited for CE/#CME #physicians #physicianassociates #nurses #pharmacists #nursepractitioners & is supported by an educational grant from the Boehringer Ingelheim Pharmaceuticals Inc and Eli Lilly Company. It is intended for healthcare professionals.

3) Faculty disclosures and statement of accreditation are provided at ckd-ce.com/disclosures/. Please FOLLOW @ckd_ce and @cardiomet_CE so you don't miss any of our unique #accredited #serialized #tweetorials, always 🆓, always from expert authors!

4) #ADA2022 was held in #NewOrleans and represented a welcome return to #FTF meetings for this vast and influential group. June 3-7 more than 6600 clinicians attended.

5) 🌟Highlight for us was the presentation of the New Joint Statement from ADA-KDIGO on the Management of #Diabetes & #CKD
@ADA_DiabetesPro @goKDIGO
Available in draft from
👉 🔓kdigo.org/wp-content/upl… 👈

6) 🙏writing groups and support staff

For @goKDIGO: @deboerih @KatherineTuttl8 @kamleshkhunti #Tami_Sadusky

For @ADA_DiabetesPro: @BakrisGeorge @JoshuaNeumiller @ConnieMRhee & @sylviaerosas

7) 👉Today we are going to focus purely on the utility and application of SGLT2i in the consensus statement.

📍If you want to read more check out this 🧵:

https://twitter.com/ckd_ce/status/1503714286757363717?s=20&t=_iAPNUOYKvZdICL6z9zviw

8a) Whatever the overall image, be it a "Greek Temple with pillars of care" (ADA), or my personal favourite "Egyptian Pyramid of Care" (KDIGO), care looks like
📍Foundation remains lifestyle change & education

📍management of risk factors

➕ Drugs to protect kidney & heart

8b) More detail at
👉🔓kdigo.org/wp-content/upl…
and from @BakrisGeorge himself at ada2022.org/live-stream/23…

9) Just a reminder that #SGLT2i have great evidence for
⤵️ adverse kidney outcomes
plus
⤵️ 🏥💔
Based on numerous trials
So go forth and #flozinate!!

👏@Sglt2inhibitorL @ChristosArgyrop @SantosGallegoMD @GoggleDocs

10) 👉What’s more than this is that #SGLT2i may delay the progression to dialysis by nearly 13 years❗️(based on data from the #CREDENCE trial)
🔓link.springer.com/article/10.100…

11) Remember Chronic Kidney Disease is common.

📍40% people living with #T2D develop #CKD

📍30% people living with #T1D develop CKD

📍half with either progress to Kidney/#HeartFailure

📍Cardiac death is much more common than renal death

🔓cjasn.asnjournals.org/content/17/7/1…

12) So ideal treatments should also ⤵️ adverse cardiovascular events as well as ⤵️ adverse kidney outcomes

13) What's new with #SGLT2i?
👉SGLT2i initiation cutoff been reduced to ≥20 mL/min/1.73m2
Rationale:
📍Benefits & risks similar across eGFR groups (other than⤵️HbA1c)
📍EMPEROR trials recruited down to eGFR ≥20
📍CREDENCE & DAPA-CKD included on-trial continuance of drug eGFR<30

14) Perhaps the major change in the ADA-KDIGO joint statement is the inclusion of mineralocorticoid antagonists (#MRA)
📍steroidal MRA (e.g. #spironolactone) for hypertension
or
📍non-steroidal MRA (e.g. #finerenone) for persistent albuminuria despite RAS blockade and #SGLT2i

15) The roles in delaying progression & improving #CV outcomes come from the pivotal trials using #finerenone

📍FIDELIO-DKD trial
📍FIGARO-DKD trial
&
📍the FIDELITY Pooled analysis

Please read more about the data in a tweetorial by @drkevinfernando
🔓

https://twitter.com/ckd_ce/status/1483778724180938752?s=20&t=d5eC06PgoCOplSynapWY2Q

16) So we now do have three pillars of slowing #DKD progression & reducing adverse cardiovascular outcomes:
1️⃣Renin-Angiotensin Blockade
2️⃣ SGLT2 Inhibition
3️⃣non-steroidal MRA
@BakrisGeorge at #ADA2022: ada2022.org/live-stream/23…

17a) Q: Does combining SGLT2i and ns-MRAs improve kidney outcomes❓
📍different mechanisms of action
📍a rodent study showed empagliflozin PLUS finerenone ⤴️survival in a DKD mouse model
📍In FIDELITY. No interaction seen between SGLT2i use or not. So benefits appear cumulative?

17b) See 🔓karger.com/Article/FullTe…
&
🔓academic.oup.com/eurheartj/arti…

18) The combination of the 3 pillars holds promise to almost halt the progression of #DKD - Well that's what @BakrisGeorge says 😊
📍The manufacturers of finerenone have initiated a Ph2 study CONFIDENCE investigating combining #empagliflozin & #finerenone
clinicaltrials.gov/ct2/show/NCT05…

19a) ⚠️Use of #RASi + #MRAs brings with it an ⤴️risk of #hyperkalaemia.
📍Although ns-MRA, like #finerenone, have a much lower risk of hyperkalaemia than steroidal MRA's
📍Finerenone was assoc. with ⤴️ discontinuation due to hyperkalaemia in the FIDELIO-DKD trial (2.3 vs 0.9%)

19b) See
🔓ahajournals.org/doi/full/10.11…
🔓academic.oup.com/eurheartj/arti…
🔓jasn.asnjournals.org/content/33/1/2…

20a) Can #SGLT2i ⤵️ #hyperkalaemia risk❓
📍SGLT2i ⤴️ distal 🧂 & water delivery, ⤴️ electronegative charge in the tubular lumen that regulates potassium excretion in the distal nephron
📍glycosuria may also ⤴️ potassium excretion
📍SGLT2i ⤴️ aldosterone so ⤵️ serum potassium

21) Discussed at #ADA2022:
👉Results of ROTATE 3
📍randomized crossover clinical trial
📍#Dapagliflozin⬇️some ⤴️ serum K+ seen with #eplerenone (MRA) tx in pts with #CKD
📍The combination also ⤵️ urine #ACR more than either drug taken on its own
🔓pubmed.ncbi.nlm.nih.gov/35440501/

22) And more #ADA2022:
👉Post hoc safety analysis by @brendonneuen #CREDENCE trial found #canagliflozin
⤵️ risk of composite of investigator-reported #hyperkalaemia events or initiation of K+ binders
⤵️ initiation of K+ binders 😊
⤵️ risk of K+>6mmol
🔓ahajournals.org/doi/full/10.11…

23) More from the ADA-KDIGO session at #ADA2022:
👉Baseline concomitant use of #SGLT2i with #finerenone associated with a ⤵️ in #hyperkalaemia events in the #FIDELIO_DKD trial, compared to non-use of SGLT2i at baseline
See 🔓pubmed.ncbi.nlm.nih.gov/34732509/

24) So #SGLT2i may be excellent agents to help prevent #hyperkalaemia in people treated with

📍RAS blockade ✅
and/or
📍MRA ✅
...although don't forget you may still need to consider potassium binders‼️

25) 👉SGLT2i treatment for heavy albuminuric CKD may even be cost-effective, meaning it may improve quality of life and reduce health care costs compared to placebo‼️
New data from #ADA2022:

26) So how are we doing here? Drinking from the firehose? Let's make sure you're keeping up!
The @ADA_DiabetesPro - @goKDIGO consensus document recommends #SGLT2i are initiated above what eGFR threshold for the treatment of CKD?
Mark your best answer!

27) #SGLT2i have what effect on hyperkalaemia seen in people with CKD treated with RAS blockers and/or MRAs?
a. Slightly⤴️ risks
b. Have no impact on hyperkalaemia risks
c. Slightly⤵️ risks

Mark your response here too & RETURN TOMORROW for the correct answers & your 🆓CE/#CME!

28) WELCOME BACK! We are reviewing key highlights of #ADA2022 with @drpatrickholmes of @GoggleDocs, who is focusing on new data re non-🫀 effects of #SGLT2i.
Did you answer yesterday's quizzes (tweets 26-7)?
The correct answer for BOTH is C.
Did you score 💯 ??
Now, ONWARD!

29) Still from the #ADA2022 @ADA_DiabetesPro-@goKDIGO session: a word about screening & treatment gaps:
📍90%+ of people with #T2DM have #eGFR testing
📍about 50% with #T2DM have #UACR tested within a year
📍Although these are🇺🇸 data, very similar data are found in the 🇬🇧

30) Furthermore, the more you screen, the more #CKD you will find.
Because #CKD is not only associated with risk of progressing to renal replacement therapy #RRT, but also ⬆️risk of adverse #CV events like #HeartFailure, we need a population health approach

31) Thinking about #population_health two more questions spring to mind:

1⃣Are the right people prescribing #SGLT2i?

2⃣Are the right people being treated with SGLT2i?

32) Are the right people prescribing #SGLT2i?
📍SGLT2i initiation has shifted from endocrinology to us in primary care ☺️. This has to be a good thing when thinking of population health❗️
📍Initiation by cardiologists and in particular #nephrologists has to improve

33) Are the right people taking #SGLT2i’s?
More concern for kidney doctors is that among pts with #CKD in 2019
📍 only 20.6% are on a RAS Blocker
⚠️ potentially reno-toxic drugs (NSAIDs & PPIs) are prescribed in 20.5 & 13.2% respectively
☹️ only 0.1% of people are on SGLT2i‼️

34) At #ADA2022 @christinelimont presented more recent prescribing data on prescribing in people with #T2DM & eGFR ≥30 from #NHANES data 🇺🇸
📍only 5.6% were taking a #SGLT2i
📍SGLT2i use didn't differ across high risk groups (CV or CKD)
📍⤵️ use in uninsured & ethnic groups 😡

35) Q. Does the out-of-pocket expense cost influence initiating #SGLT2i in patients #T2DM + established #ASCVD?
A. Yes 😡
👉Analysis by Prof. Jing Luo presented #ADA2022:
👉Retrospective cohort study
👉Mainly in Medicare Advantage (🇺🇸 data)
🌟⤴️costs associated with⤵️initiation

36) So which of these appears NOT to be a barrier for someone being initiated on a SGLT2i?

a. Being over 75 years of age
b. High out-of-pocket costs
c. Being of white European descent
d. Being of black African descent

Answer before you scroll ⤵️

37) The correct answer is c—being of white European descent is NOT a barrier to being initiated on #SGLT2i therapy.

So . . .

38) Q. Can #SGLT2i help reduce the risk of Kidney stones?
A. Could do, per poster presentation at #ADA2022‼️
#CaReMe
👉SGLT2i ⤵️ kidney stones when compared to:
📍DPP4i
📍GLP-1RA

In a propensity matched cohort study:

39) More #ADA2022:
Q. Does frailty impact on extended #MACE outcomes of #SGLT2i (i.e. including all-cause ☠️ &🏥💔)?
A. Relative risk ⤵️remains the same, although absolute benefits appear greater in frail patients‼️
⚠️Population based study - Medicare (🇺🇸)
✅ Propensity matching

40a) Moving on to another area of growing importance in #type2diabetes, namely Non-alcoholic Liver disease (#NAFLD: for more info/credit, see cardiometabolic-ce.com/nashbonus/ by @mcharltonmd).

Can #SGLT2i help with this condition?

40b) I will try to summarise a great session at #ADA2022 by one of the friends of @GoggleDocs - @drshafikuchay

41) #SGLT2i may prevent the development of #NAFLD in #T2DM
📍best evidence comes from a large population study in 🇬🇧
👉Compared to users of #DPP4i, SGLT2i use was assoc with a relative reduction in risk of developing NAFLD of 22%

🔓diabetesjournals.org/care/article-a…

42) 👉#SGLT2i as a treatment for #NAFLD
📍Data from #MRI studies

#SGLT2i:
⤵️ Liver Fat
⤵️ Liver Enzymes
⤵️ Inflammatory and fibrotic markers

43) More #ADA2022:👉#SGLT2i as a tx for #NAFLD
📍long-term data from #EMPA_REG_OUTCOME study
#Empgagliflozin assoc. with
⤵️ALT 2.22u/L at 28 wks
⤵️ALT 1.26u/L at 164 wks
⤵️greatest is highest ALT quartile
👉 ALT⤵️ independent of changes in weight/HbA1c
🔓link.springer.com/content/pdf/10…

44) 👉SGLT2i as a treatment for NAFLD/NASH in #T2DM:
📍Multi-centre RCT in 🇯🇵
📍n=55
📍Liver biopsy study😊
#Ipragliflozin use assoc. with
⤵️ Liver Fibrosis
⤵️ Progression from NAFLD➡️ NASH
⤴️ remission from NASH

🔓aasldpubs.onlinelibrary.wiley.com/doi/10.1002/he…

45) So how does SGLT2i ⤵️ Liver Fat❓
📍multiple mechanisms:
👉 Glycosuria➡️Insulin⤵️
👉⤴️ Glucagon/Insulin ratio ➡️ Ketogenesis
👉 ⤴️ Hypothalamic insulin sensitivity ➡️ Vagal nerve tone⤴️

🔓diabetesjournals.org/care/article/4…

46) In summary #SGLT2i
📍⤵️ risk of developing #NAFLD
📍⤵️ Fibrosis
📍⤵️ portal hypertension

As well as
⤵️ #HbA1c
⤵️ Adverse #CV events
⤵️ Adverse kidney events

47) At #ADA2022 David Cherney presented interesting data from the now published BETWEEN Study, aimed at testing theory that #RAS blockade (#rampiril) & #SGLT2i (#empagliflozin) had complementary effects of in restoration of Tubuloglomerular feedback
📍Only pts with #T1D recruited

48) Randomised, double-blind, placebo controlled, cross-over trial
📍Primary outcome effect on empa+ramipril on GFR vs placebo+ramipril treatment
📍each phase measured:
-GFR
-Tubular Na handling
-Arterial stiffness
-HR variability
-Cardiac output
-plasma & urine biochem

49) 👉Results:

Expected GFR ⤵️
⬇️Oxidative stress markers
Additional ⤵️BP
⤵️ Total peripheral resistance.

full paper now published👇

🔓ahajournals.org/doi/abs/10.116…

50) 👉Conclusion
David Cherney was right all along: #RAS blockade & #SGLT2i work together to restore tubuloglomerular feedback 👏👏👏

✅Consistent with protective ⤵️ intraglomerular pressure
⚠️ mechanistic study
⚠️ DKA risk with SGLT2i in #T1D high, but may ⤵️ cardiorenal risk

51) So, in parting . . . in people with #T1D and kidney #hyperfiltration the addition of a #SGLT2i in people taking ramipril causes?

a) ⤵️ Intraglomerular pressure
b) ⤵️ Total peripheral resistance
c) ⤵️ Oxidative stress markers
d) All the above

52) Oh yeah, you got this . . . it's D, all of the above. And with that triumph, you can go and claim your 🆓0.75h CE/#CME #physicians #physicianassociate #nurses #nursepractitioners #pharmacists

53) So go to ckd-ce.com/dkd14_ADA22b/ and claim what is yours! And FOLLOW @ckd_ce and @GoggleDocs for the latest in #cardiorenal and #cardiometabolic education! I am @drpatrickholmes, and I thank you for joining us!