2) This program is intended for healthcare professionals and is supported by an educational grant from Boehringer Ingelheim Pharmaceuticals Inc. and Eli Lilly Company. See archived programs, all by expert authors, still available for credit at https://t.co/jFwbLEcQSS.
β @CKD_ce (@ckd_ce) June 7, 2022
4) See our previous tweetorials for extensive discussions of #T2D & the prevention and management of #heartfailure, foundations and management of #DKD, and role of #SGLT2i in #cardiometabolic medicine.https://t.co/I1LleFSyzyhttps://t.co/OkQ3KKGWs3
β @CKD_ce (@ckd_ce) June 7, 2022
Yes . . . even MOREπCE/CME!
6) T2D does not begin with the 1st abnormal #A1c; it is often preceded by years/decades of #insulin resistance & other metabolic diseases. T2D prevalence is expected to πΌπΌ given the tidal wave of #obesity in the πΊπΈ.
β @CKD_ce (@ckd_ce) June 7, 2022
See πhttps://t.co/z8uvvO98Xm and πhttps://t.co/IEuf4iDsAB pic.twitter.com/VWn7Vuq6J7
8) Answer *D*: Ralph DeFronzo famously described the βominous octetβ in 2009 and helped shift our understanding of T2D to a *multiorgan* process that leads to disordered energy metabolism. It is not simply a beta cell issue.
β @CKD_ce (@ckd_ce) June 7, 2022
See πhttps://t.co/j39tbRfL7K pic.twitter.com/QaUVBDqPTt
10) It's B: While #SGLT2i actually help address multiple organ dysfunctions, their primary impact in glycemic control occurs at the #kidney. Letβs explore what happens to the kidney in the development of #T2D. pic.twitter.com/fhhwOrOeBY
— @CKD_ce (@ckd_ce) June 7, 2022
12) For those who πphysiology: Sodium cotransport allows for glucose to be transported against an uphill gradient into the tubular epithelial cell. Glucose then leaves via facilitated diffusion using GLUT-2 on the basolateral membrane.
β @CKD_ce (@ckd_ce) June 7, 2022
See πhttps://t.co/tzyw99l5Ep pic.twitter.com/iN7Bx5WYMh
14) However, in #T2D, pathological maladaptations lead to an πΌ renal threshold for glucosuria. This may be due to chronic πΌ plasma glucose filtration leading to an adaptive πΌ expression of SGLT2 and therefore πΌ reuptake capacity and activity.
β @CKD_ce (@ckd_ce) June 7, 2022
See πhttps://t.co/MgmLDX6Bjh pic.twitter.com/Ho2nOOwD4H
16) This medication class was developed and better understood thanks to work related to #phlorizin, a compound found in the root bark of ππtrees known to cause glucosuria, and the rare genetic disorder familial renal glucosuria. See πhttps://t.co/1YYzDI8W19 pic.twitter.com/r85U1ZsXrS
β @CKD_ce (@ckd_ce) June 7, 2022
18) Now a quick poll: How much #A1c lowering can be expected from this class?
β @CKD_ce (@ckd_ce) June 7, 2022
20) Welcome back! I am @tmodarressi, we are discussing standards of care for treating #T2D with #SGLT2i‘s, and YOU are earning πCE/#CME! pic.twitter.com/nNneCSO1H8
β @CKD_ce (@ckd_ce) June 8, 2022
22) It’s B: In general, these agents show modest improvements in A1c, approximately 0.6-1.0%, and are overshadowed in potency of glycemic control by #GLP-1 receptor agonists (such as #semaglutide and #dulaglutide).https://t.co/01FrX4AUeG
β @CKD_ce (@ckd_ce) June 8, 2022
24) Several large studies have cast doubt on the effectiveness of preventing #macrovascular risk by forcing #A1c lower and lower. Our newer approaches and standards have a heavy focus on *how* we lower sugars rather than just to what level we lower to.
β @CKD_ce (@ckd_ce) June 8, 2022
26) A critical statement has been added to @AmDiabetesAssn guidelines in recent years, highlighted below, as studies have shown various #cardiometabolic benefits of #SGLT2 receptor inhibition regardless of baseline glycemic control. pic.twitter.com/cZEwW5mjWA
β @CKD_ce (@ckd_ce) June 8, 2022
27b) . . . as first-line monotherapy in appropriate patients (although in the US many insurers will require metformin use or a documented reason why metformin cannot be used in order to approve).
β @CKD_ce (@ckd_ce) June 8, 2022
29) As we see in these practice guidelines, the use of #SGLT2i should be particularly prioritized in patients with or at high risk for #heartfailure, #CKD, or #atherosclerotic #cardiovascular disease.
β @CKD_ce (@ckd_ce) June 8, 2022
31) Again, the effects on these comorbidities are potent and largely *independent* of their effects on glycemic control. This is a critical point.
β @CKD_ce (@ckd_ce) June 8, 2022
See π https://t.co/H8xgdMrEkz (left) and πhttps://t.co/ZL0Op6x0SW (right) pic.twitter.com/aN5t34JHFf
33) How they work to reduce these risks is beyond the scope of this tweetorial, but here are some references to dive deeper below:
β @CKD_ce (@ckd_ce) June 8, 2022
πhttps://t.co/s3ZwvUtMnV
πhttps://t.co/aTKe1ACQhE
πhttps://t.co/vH9Z4SPSAt pic.twitter.com/WXa07BTkwg
35a) 1. Soon after #SGLT2i initiation, there will be a dip in eGFR β¬ οΈmechanism of renoprotection of this class (similar to changes seen with #ACEi/ARB initiation). The magnitude of the dip varies, but has not been shown to be associated with safety concerns.
β @CKD_ce (@ckd_ce) June 8, 2022
36) I @tmodarressi tend to follow the strategies outlined below by Drs. Hiddo Heerspink and David Cherney, two very well-known researchers in the SGLT2i world.
β @CKD_ce (@ckd_ce) June 8, 2022
See πhttps://t.co/LYdWgr348c pic.twitter.com/9MpSMlcg6E
38) 3. Euglycemic #DKA is rare, but when it happens it is typically during extended fasts. Therefore, many clinicians will advise discontinuation a few days before surgery and skipping if experiencing upper GI illness or poor PO intake for other reasons.
β @CKD_ce (@ckd_ce) June 8, 2022
πhttps://t.co/rLQewIvabp
40) So what may be next for the #SGLT2i class strictly in the glycemia world? Intriguing data from the DAPA-HF trial (which enrolled patients both with and without #T2D) showed a 32% reduction in the incidence of new T2D.
— @CKD_ce (@ckd_ce) June 8, 2022
See πhttps://t.co/m5zM57ZcRJ pic.twitter.com/UyDZQEpaHD
42) Further, we know that many pts w T2D develop CV diseases at much younger ages (see the curves shifted left below). Can pushing tx into earlier phases of the pathophysiological life cycle preserve health and prevent these burdensome diseases?
— @CKD_ce (@ckd_ce) June 8, 2022
(from πhttps://t.co/uCMUisesu5) pic.twitter.com/ue4d6oyZ4x
44) And that's it! You just earned 0.5hr CE/#CME! Go to https://t.co/ufD2I6aMpg and claim your certificate! And follow @cardiomet_ce and @ckd_ce for the BEST continuing education on Twitter from expert authors! I am @tmodarressi. Thanks for joining!
— @CKD_ce (@ckd_ce) June 8, 2022