The metabolic and hemodynamic correlates of SGLT2i-mediated UGE in patients with diabetes are not well understood. Accordingly, in this post hoc analysis, we measured UGE in 66 T2D, 37 T1D, and 25 nondiabetic (ND) participants under baseline conditions and following treatment with an SGLT2i (empagliflozin, 25 mg/d, EMPA). Measurements were taken during 3 h of fasting and 5 h of a mixed meal absorption (T2D and ND) or under usual clinical conditions in patients with T1D. Fractional glucose excretion (FEGlu) was obtained as the ratio of UGE to the filtered glucose load (=GFR x plasma glucose concentration [G]). In T1D participants only, ERPFPAH and GFRINULIN were measured and intraglomerular pressure (PGLO) estimated.

With EMPA, FEGlu was 38±12% and 46±11% in T2D (fasting and post meal, respectively), 26±11% and 36±8% in ND, and 45±21% in T1D. In the pooled T1D, T2D and ND cohort, overall effect of EMPA on FEGlu was 39±11%; in this model, [G] was a positive determinant (FEGlu=34% at a [G] of 100 mg/dL and 44% at a [G] of 200 mg/dL, r=0.38, p<0.0001), whereas presence of T1D, T2D or ND was not. After adjusting for [G], plasma insulin concentration was also a positive determinant of FeGlu (r=0.12, p=0.01), adding 3% to FEGlu at the mean post meal plasma insulin of 50 µU/mL in T2D and ND; likewise, in T1D, FEGlu was related to the mean daily insulin dose (r=0.41, p<0.01). As described in previous work, in T1D, EMPA decreased ERPF and increased renal vascular resistance (p<0.01). Estimated PGLO was reduced (59.0±6.7 to 56.5±4.6 mmHg, p=0.038), and its change from baseline was associated with a larger increment in FEGlu (r=0.48, p=0.003.

In conclusion, SGLT2i effects on renal glucose reabsorption are consistent across the spectrum of glucose tolerance. Moreover, FEGlu is a function of ambient hyperglycemia and, to a lesser extent, insulinemia. Finally, in T1D, decrements in renal hyperfiltration are related to greater glycosuria, possibly as a function of natriuresis.


Y. Lytvyn: None. A. Lytvyn: None. E.O. Muscelli: None. B.A. Perkins: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Boehringer Ingelheim International GmbH, Insulet Corporation. Research Support; Self; Boehringer Ingelheim International GmbH. Other Relationship; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Medtronic, Novo Nordisk Inc., Sanofi. D. Cherney: Other Relationship; Self; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Prometic Life Sciences Inc., Sanofi. E. Ferrannini: None.

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