Decision letter for "Urinary glucose excretion contributions of SGLT2 <i>vs</i> . SGLT1 transporters: a quantitative systems pharmacology analysis in healthy and T2DM subjects administered SGLT2 inhibitors"

Abstract Background and Aims The use of sodium glucose co-transporter 2 inhibitors (SGLT2i) is consistently associated with decrease of serum uric acid levels due to increase uricosuria coupled to glucosuria by mechanisms that are still incompletely understood. In diabetic kidney disease these drugs had shown only modest effects on HbA1c control allegedly due insufficient glucosuric effect. However, renal patients also benefit from hypouricemic effect of SGLT2 inhibitors. The aim of this study was to evaluate glucosuria and uricosuria in DKD patients treated with SGLT2i Method We prospectively analyzed glucose and urate fractional excretions of patients that were to initiate treatment with an SGLT2i, using fractional excretion classical formulas. Patients on GLP1ar or any uricosuric agent including losartan were excluded. All participants gave written consent. Results 37 patients (75.7% male) diagnosed from DKD were included, median age 69.6 years IQR [65.6-73.4], median CKD-EPI eGFR 54,10 ml/min/1,72 m2 [ 41,12- 69,68 IQR] and UACR 137 [49-443] mg/g. SGLT2i used was 53.3% dapagliflozin, 24.4% empagliflozin or 22.2% canagliflozin and mean follow- up was 1.5 years.Serum uric acid levels didn’t show any significative difference along time in this group of patients (6.8 vs 6.3; p 0.4) and %HbA1C was only slightly decreased by month 12 (7.1 vs 6.7; p0.03). Urinary uric acid fractional excretion increased by month 3 and was stabilized till month 12 when this effect seemed to decrease (figure and table) Glucosuria exhibit a similar effect: Urinary glucose fractional excretion increased immediately after the addition of the drug and stabilized over time decreasing at the end of the observation period. Spearman rank correlation test indicated dependency glucosuria and uricosuria (Spearman´s rho 0,24, p 0,03). GFR estimated by CKD-EPI kept stable along the study indicating that loss of uricosuric and glucosuric effect are independent of GFR Conclusion We conclude that uric acid renal excretion is significantly increased in patients treated with SGLT2i even in the presence of DKD but tends to diminish over time, feature that was also observed on urinary glucose excretion and that showed no correlation with GFR. Over-expression of SGLT1 after SGLT2 inhibition has been described in animal models of DKD. Whether this extends to human tubule and explains these results need to be further investigated

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155-LB: The Increase in Endogenous Glucose Production with SGLT2 Inhibition Is Unchanged by Renal Denervation but Highly Correlates to Urinary Glucose Excretion

Diabetes ◽

10.2337/db19-155-lb ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 155-LB

Author(s):

CAROLINA SOLIS-HERRERA ◽

MARIAM ALATRACH ◽

CHRISTINA AGYIN ◽

HENRI HONKA ◽

RUPAL PATEL ◽

...

Keyword(s):

Renal Denervation ◽

Glucose Production ◽

Endogenous Glucose Production ◽

Urinary Glucose Excretion ◽

Urinary Glucose ◽

Sglt2 Inhibition ◽

Endogenous Glucose ◽

Glucose Excretion

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