Effect of Canagliflozin on Urinary Albumin Excretion in Japanese Patients with Type 2 Diabetes Mellitus and Microalbuminuria: A Pilot Study

• Published in: Diabetes technology & therapeutics Vol. 20; no. 10; p. 681
• Main Authors: Osonoi, Takeshi, Gouda, Maki, Kubo, Mamiko, Arakawa, Kenji, Hashimoto, Toshio, Abe, Masanori
• Format: Journal Article
• Language: English
• Published: United States 01.10.2018
• Subjects: Adult; Aged; Albuminuria - drug therapy; Asian Continental Ancestry Group; Blood Glucose - analysis; Blood Pressure - drug effects; Body Weight - drug effects; Canagliflozin - adverse effects; Canagliflozin - therapeutic use; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - urine; Diabetic Nephropathies - prevention & control; Diabetic Nephropathies - urine; Female; Glycated Hemoglobin A - analysis; Humans; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Kidney Function Tests; Male; Middle Aged; Pilot Projects; Young Adult; Type 2 diabetes; Renoprotective effect; Nephropathy; Albuminuria; Canagliflozin; SGLT2 inhibitor
• DOI: 10.1089/dia.2018.0169

Albuminuria characterizes the progression of kidney injury. The effect of canagliflozin on the excretion of microalbumin was assessed for investigating its renoprotective potential in Japanese patients with type 2 diabetes mellitus (T2DM). Twenty Japanese patients with T2DM and microalbuminuria were enrolled and administered with 100 mg of canagliflozin once a day for 12 weeks. These subjects were admitted to the clinic at the start and end of the treatment period for 24-h urine collection. The primary endpoint was the percentage change in geometric mean 24-h urinary albumin excretion from baseline to week 12. The urinary albumin level decreased by 42.0% (95% confidence interval: 21.9-57.0; P = 0.0011) after 12 weeks of canagliflozin treatment. A number of blood and urinary parameters also significantly decreased, including hemoglobin A1c, fasting plasma glucose, estimated glomerular filtration rate, and creatinine clearance, while hematocrit was elevated. Among the biomarkers associated with kidney injury and inflammation, the urinary level of the oxidative stress marker 8-hydroxy-2'-deoxyguanosine was also decreased. There were no meaningful correlations noted between changes in urinary albumin excretion and other parameters/biomarkers. No severe adverse events were reported over the 12-week treatment period. The results of this study indicate that canagliflozin decreases microalbuminuria in Japanese patients with T2DM. Albuminuria could be reduced as a result of changes in various physiological pathways; therefore, it is imperative that future, large-scale, studies attempt to determine the detailed mechanisms involved. Canagliflozin may offer a novel therapeutic option for Japanese patients with T2DM and incipient nephropathy.