Empagliflozin and Kinetics of Renal Glucose Transport in Healthy Individuals and Individuals With Type 2 Diabetes

• Published in: Diabetes (New York, N.Y.) Vol. 66; no. 7; pp. 1999 - 2006
• Main Authors: Al-Jobori, Hussein, Daniele, Giuseppe, Cersosimo, Eugenio, Triplitt, Curtis, Mehta, Rucha, Norton, Luke, DeFronzo, Ralph A., Abdul-Ghani, Muhammad
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.07.2017
• Subjects: Antidiabetics; Benzhydryl Compounds - therapeutic use; Blood Glucose - metabolism; Case-Control Studies; Complications; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Fasting; Female; Glucose; Glucose - metabolism; Glucose Clamp Technique; Glucose transport; Glucose transporter; Glucosides - therapeutic use; Glycosuria; Humans; Hyperglycemia; Hypoglycemic Agents - therapeutic use; Kidney - metabolism; Kidneys; Kinetics; Male; Medical treatment; Middle Aged; Reabsorption; Sodium; Sodium-glucose cotransporter; Sodium-Glucose Transporter 2 Inhibitors; Urine
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db17-0100

Renal glucose reabsorption was measured with the stepped hyperglycemic clamp in 15 subjects with type 2 diabetes mellitus (T2DM) and 15 without diabetes after 2 days and after more chronic (14 days) treatment with empagliflozin. Patients with T2DM had significantly greater maximal renal glucose transport (TmG) compared with subjects without diabetes at baseline (459 ± 53 vs. 337 ± 25 mg/min; P < 0.05). Empagliflozin treatment for 48 h reduced the TmG in both individuals with and without diabetes by 44 ± 7 and 53 ± 6%, respectively (both P < 0.001). TmG was further reduced by empagliflozin in both groups on day 14 (by 65 ± 5 and 75 ± 3%, respectively). Empagliflozin reduced the plasma glucose concentration threshold for glucose spillage in the urine similarly in individuals with T2DM and without diabetes to <40 mg/dL, which is well below the normal fasting plasma glucose concentration. In summary, sodium-glucose transporter-2 inhibition with empagliflozin reduces both TmG and threshold for glucose spillage in the urine in patients with T2DM and those without diabetes.