Faculty Opinions recommendation of Characterization and implications of the initial estimated glomerular filtration rate 'dip' upon sodium-glucose cotransporter-2 inhibition with empagliflozin in the EMPA-REG OUTCOME trial.

Background The frequency of the initial short‐term decline in estimated glomerular filtration rate (eGFR), eGFR dip, following initiation of sodium‐glucose cotransporter‐2 inhibitors (SGLT2i) and its clinical implications in real‐world practice are not clear. Methods and Results We built a cohort of 36 638 new users of SGLT2i and 209 025 new users of other antihyperglycemics. Inverse probability weighting was used to estimate the excess rate of eGFR dip, risk of the composite cardiovascular outcome of nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, or all‐cause mortality, and risk of the composite kidney outcome of eGFR decline >50%, end‐stage kidney disease, or all‐cause mortality. In the first 6 months of therapy, compared with other antihyperglycemics, excess rates of eGFR dip >10% and eGFR dip >30% were 9.86 (95% CI: 8.83–11.00) and 1.15 (0.70–1.62) per 100 SGLT2i users, respectively. In mediation analyses that accounted for eGFR dipping, SGLT2i use was associated with reduced risk of cardiovascular and kidney outcomes (hazard ratio, 0.92 [0.84–0.99] and 0.78 [0.71–0.87], respectively); the magnitude of the association reduced by eGFR dipping was small for both outcomes. SGLT2i was associated with reduced risk of both outcomes in those with higher than average probability of eGFR dip >10% or 30%. Compared with discontinuation, continued use of SGLT2i at 6 months was associated with reduced risk of cardiovascular and kidney outcomes in those with no eGFR dip or eGFR dip ≤10%, in those with eGFR dip >10%, and in those with eGFR dip >30%. Conclusions The salutary association of SGLT2i with cardiovascular and kidney outcomes was maintained regardless of eGFR dipping; concerns about eGFR dipping should not preclude use, and occurrence of eGFR dip after SGLT2i initiation may not warrant discontinuation.

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MO652EFFECT OF ESTIMATED GLOMERULAR FILTRATION RATE (EGFR) ON HEMOGLOBIN CHANGE INDUCED BY SODIUM-GLUCOSE COTRANSPORTER 2 INHIBITORS (SGLT2I)

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab094.0020 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Alba Maroto ◽

Ester Domenech ◽

Maria Marques Vidas ◽

Paula López ◽

Jose' M Portoles

Keyword(s):

Chronic Kidney Disease ◽

Renal Function ◽

Multivariate Analysis ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Filtration Rate ◽

Estimated Glomerular Filtration Rate ◽

Sglt2 Inhibitors ◽

Sodium Glucose Cotransporter ◽

Main Determinants

Abstract Background and Aims The use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) is associated with increase of hemoglobin (Hb) levels and this effect has been related to improvement of tubulointerstitial hypoxia and increase on EPO production. Chronic kidney disease (CKD) associated anemia is mainly due to decreased EPO synthesis. The aim of this study was to assess if the degree of Hb increase induced by SGLT2i is higher on T2DM patients with decreased estimated glomerular filtration rate (eGFR). Method We analyzed the changes on Hb after 12 months of SGLT2i treatment in T2DM patients with different degrees of eGFR. All patients were on maximum tolerated RAA system blockade, and none was on erythropoiesis or iron therapy. Results 62 patients were include, age 67,6 ± 12,3 years, 72.6% males, eGFR CKD EPI 62,9 ± 21 (21-108) ml/min/1.73m2. Type of SGLT2i was dapagliflozin (46.8%), canagliflozin (30,5%) and empagliflozin (22,6%). 7 patients discontinued SGLT2i therapy and 62 were finally include in the analysis. Treatment with SGLT2i induced increase of Hb levels ( ΛHb 0,57 mg/dl SE 0,17 95% CI 0,25-0,93, p 0,001) independently of eGFR (aR2 0.02 p ns) In the multivariate analysis, initial eGFR, and basal Hb were the main determinants of the Hb increase induced by SGLT2i treatment (aR2 0,29). eGFR (≤60 vs >60 ml/min/173) or type of SGLT2i did not modified ΛHb Conclusion We conclude that SGLT2 inhibitors induce increase on Hb level independently of eGFR, in patients with preserved renal function, by mechanisms that are yet to be determined.

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