title: Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus.
abstract: BACKGROUND
  The primary objective of this mechanistic open-label, stratified clinical trial was to determine the effect of 8 weeks' sodium glucose cotransporter 2 inhibition with empagliflozin 25 mg QD on renal hyperfiltration in subjects with type 1 diabetes mellitus (T1D).
  
  
  RESULTS
  Inulin (glomerular filtration rate; GFR) and paraaminohippurate (effective renal plasma flow) clearances were measured in individuals stratified based on having hyperfiltration (T1D-H, GFR ≥ 135 mL/min/1.73m(2), n=27) or normal GFR (T1D-N, GFR 90-134 mL/min/1.73m(2), n=13) at baseline. Renal function and circulating levels of renin-angiotensin-aldosterone system mediators and NO were measured under clamped euglycemic (4-6 mmol/L) and hyperglycemic (9-11 mmol/L) conditions at baseline and end of treatment. During clamped euglycemia, hyperfiltration was attenuated by -33 mL/min/1.73m(2) with empagliflozin in T1D-H, (GFR 172±23-139±25 mL/min/1.73 m(2), P<0.01). This effect was accompanied by declines in plasma NO and effective renal plasma flow and an increase in renal vascular resistance (all P<0.01). Similar significant effects on GFR and renal function parameters were observed during clamped hyperglycemia. In T1D-N, GFR, other renal function parameters, and plasma NO were not altered by empagliflozin. Empagliflozin reduced hemoglobin A1c significantly in both groups, despite lower insulin doses in each group (P≤0.04).
  
  
  CONCLUSIONS
  In conclusion, short-term treatment with the sodium glucose cotransporter 2 inhibitor empagliflozin attenuated renal hyperfiltration in subjects with T1D, likely by affecting tubular-glomerular feedback mechanisms.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT01392560.
authors: Department of Medicine, Division of Nephrology (D.Z.I.C., M.M., V.L., A.L.) and the Department of Medicine, Division of Endocrinology (B.A.P.), Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada; Boehringer Ingelheim Canada Ltd./Ltée, Burlington, Ontario, Canada (N.S.); Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT (N.M.F., M.v.E.); and Boehringer Ingelheim Pharma GmbH & Co.KG, Ingelheim, Germany (H.J.W., O.E.J., U.C.B.).
authors: David Z I
authors: DZ
authors: Cherney
authors: Bruce A
authors: BA
authors: Perkins
authors: Nima
authors: N
authors: Soleymanlou
authors: Maria
authors: M
authors: Maione
authors: Vesta
authors: V
authors: Lai
authors: Alana
authors: A
authors: Lee
authors: Nora M
authors: NM
authors: Fagan
authors: Hans J
authors: HJ
authors: Woerle
authors: Odd Erik
authors: OE
authors: Johansen
authors: Uli C
authors: UC
authors: Broedl
authors: Maximilian
authors: M
authors: von Eynatten
mesh_terms: D000328:Adult; D001559:Benzhydryl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology*; D015309:Glucose Clamp Technique / Q000379:methods; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051297:Sodium-Glucose Transporter 2 / Q000502:physiology*; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C570240:empagliflozin
keywords: SGLT2 protein; diabetes mellitus; diabetic nephropathies; hypertension, renal; nitric oxide; renin-angiotensin system