Renal Hemodynamic Effect of Sodium-Glucose Cotransporter 2 Inhibition in Patients With Type 1 Diabetes Mellitus

• Published in: Circulation (New York, N.Y.) N.Y.), 2014-02, Vol.129 (5), p.587-597
• Main Authors: Cherney, David Z.I, Perkins, Bruce A, Soleymanlou, Nima, Maione, Maria, Lai, Vesta, Lee, Alana, Fagan, Nora M, Woerle, Hans J, Johansen, Odd Erik, Broedl, Uli C, von Eynatten, Maximilian
• Format: Article
• Language: English
• Subjects: Adult; Associated diseases and complications; Benzhydryl Compounds - pharmacology; Benzhydryl Compounds - therapeutic use; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - physiopathology; Diabetes. Impaired glucose tolerance; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Glomerular Filtration Rate - drug effects; Glomerular Filtration Rate - physiology; Glucose Clamp Technique - methods; Glucosides - pharmacology; Glucosides - therapeutic use; Hemodynamics - drug effects; Hemodynamics - physiology; Humans; Kidney - drug effects; Kidney - physiology; Kidneys; Male; Medical sciences; Nephrology. Urinary tract diseases; Sodium-Glucose Transporter 2 - antagonists & inhibitors; Sodium-Glucose Transporter 2 - physiology; Treatment Outcome; Urinary system involvement in other diseases. Miscellaneous; Young Adult
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.113.005081

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). METHODS AND 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, n=27) or normal GFR (T1D-N, GFR 90–134 mL/min/1.73m, 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 with empagliflozin in T1D-H, (GFR 172±23–139±25 mL/min/1.73 m, P