Thread by @priti899, SGLT2i are emerging as a promising agent to prevent and the [...]

SGLT2i

are emerging as a promising agent to prevent and

the progression of DKD
Ever wondered
What do they do to electrolytes

Why r these diuretics not associated with electrolyte depletion

Let's dive deeper

#medtwitter #NephMadness #SGLT2iRegion

SGLT2i are emerging as a promising agent to prevent and the progression of DKDEver wonderedWhat do they do to electrolytesWhy r these diuretics not associated with electrolyte depletionLet's dive deeper #medtwitter #NephMadness #SGLT2iRegion

What is the impact of SGLT2i on Na and water hemostasis?

First, let’s revisit, how Na and glucose are handled in the nephron

100% of the filtered glucose is reabsorbed along the nephron (90%, via SGLT2 in PCT)

1 Na+ ion for every glucose molecule gets absorbed from the lumen

In PCT 60 - 80% of sodium is reabsorbed

First, let’s revisit, how Na and glucose are handled in the nephron 100% of the filtered glucose is reabsorbed along the nephron (90%, via SGLT2 in PCT) 1 Na+ ion for every glucose molecule gets absorbed from the lumen In PCT 60 - 80% of sodium is reabsorbed

Now let’s find out what happens with SGLT2 inhibition

With SGLT2 inhibition in PCT, Na/glucose, pass distally

↑ delivery of Na to macula densa

vasoconstriction of afferent artery and Natriuresis and glycosuria

Now let’s find out what happens with SGLT2 inhibition With SGLT2 inhibition in PCT, Na/glucose, pass distally ↑ delivery of Na to macula densa vasoconstriction of afferent artery and Natriuresis and glycosuria

Although negative Na balance, there are NO changes in serum Na levels in clinical studies.

Notice anything odd?

Possible mechanism: Due to the redistribution of Na from intracellular to extracellular spaces. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839176/

SGLT2 Inhibitors and Cardiovascular Risk: Lessons Learned From the EMPA-REG OUTCOME Study

Although cardiovascular (CV) mortality is the principal cause of death in individuals with type 2 diabetes (T2DM), reduction of plasma glucose concentration has little effect on CV disease (CVD)...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839176/

What is the effect of SGLT2i on serum K levels?

Slight

in K ( 0.6 - 2.8%) was found in some SGLT2i trials with

canagliflozin (not with empagliflozin and dapagliflozin )

https://doi.org/10.1185/03007995.2014.919907

Slight in K ( 0.6 - 2.8%) was found in some SGLT2i trials with canagliflozin (not with empagliflozin and dapagliflozin ) https://doi.org/10.1185/03007995.2014.919907

Although

in K is small, careful monitoring is required in patients with

CKD

Patients taking concomitant medications associated with ↑ K level (k sparing diuretics/ RAAS blockers )

Mechanism of hyperkalemia

Diuresis-associated hemoconcentration

Decrease insulin secretion→ shift to extracellular fluid

What is the effect of SGLT2i on serum Phosphate levels?

let’s try to understand the effect of SGLT2i on PO4 homeostasis.

SGLT2 Inhibition

↓ Proximal Na reabsorption

↑availability of Na to be reabsorbed with PO4 via the NaPi IIa co-transporter in PCT.

let’s try to understand the effect of SGLT2i on PO4 homeostasis.SGLT2 Inhibition ↓ Proximal Na reabsorption ↑availability of Na to be reabsorbed with PO4 via the NaPi IIa co-transporter in PCT.

A recent study with dapagliflozin for 6 weeks showed

↑ S Po4 levels - 9%

↑ FGF‐23 -19%

↑ PTH -16%
https://www.ncbi.nlm.nih.gov/pubmed/30559106?dopt=Abstract

In conclusion
FGF23 is stimulated by

S Po4 levels → phosphaturia and ↓ 1,25(OH)2 D and ↑ PTH to maintain the phosphate balance

https://www.thelancet.com/journals/landia/article/PIIS2213-8587(14)70227-X/fulltext