11. Tubular workload and Hypoxia
Functional recovery of tubulointerstitial fibroblasts with SGLT2 inhibitor therapy (reverse remodeling). SGLT2 inhibitor
therapy suppresses oxygen consumption by the proximal tubules and improves tubulointerstitial hypoxia.
13. Anti-inflammatory Pathway
SGLT-2i reduce levels of nuclear factor kB (NFkB),IL-6,
Monocyte chemoattractant protein 1 (MCP-1), and other factors
implicated in inflammation and tissue fibrosis in experimental
models of diabetes.
Hyperuricemia may induce kidney inflammation and has been
reported to be a risk factor for incident DKD in T2DM and SGLT-2i
causes uricosuria.
16. Dose adjustment of SGLT-2i and GLP-
1RA in renal failure patients :
For SGLT-2i
When eGFR >30, no dose adjustment required.
When eGFR <30, contraindicated.
It is reasonable to withhold SGLT2i during times of prolonged fasting,
surgery, or critical medical illness (when patients may be at greater
risk for ketosis).
A reversible decrease in the eGFR with commencement of SGLT2i
treatment may occur and is generally not an indication to discontinue
therapy.
17. For GLP-1RA : (According to ADA guideline)
> No dose adjustment for dulaglutide, liraglutide and semaglutide .
> When eGFR < 30, avoid exenatide, lixisenatide.
19. Which one has more Renoprotective Effect ?
(SGLT-2i or GLP-1RA)
Although no trial has directly compared SGLT-2i with GLP-1RA, a
meta-analysis of 8 cardiovascular trials found a 38% and 18% lower
risk of new-onset UACR >300mg/g, doubling of S. creatinine, a
>40% decline in eGFR, kidney failure with replacement therapy or
death from kidney diseases for SGLT-2i and GLP-1RA, respectively.
Thus, SGLT-2i appears to be more effective in slowing kidney
disease progression and should be considered before GLP-1RA.
