Efficacy and Safety of Canagliflozin in Patients with Type 2 Diabetes and Stage 3 Nephropathy

• Published in: American journal of nephrology Vol. 40; no. 1; pp. 64 - 74
• Main Authors: Yamout, Hala, Perkovic, Vlado, Davies, Melanie, Woo, Vincent, de Zeeuw, Dick, Mayer, Cristiana, Vijapurkar, Ujjwala, Kline, Irina, Usiskin, Keith, Meininger, Gary, Bakris, George
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2014
• Subjects: Aged; Blood Glucose - metabolism; Blood Pressure; Body Weight; Canagliflozin; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diabetic Nephropathies - etiology; Diabetic Nephropathies - metabolism; Female; Glomerular Filtration Rate; Glucosides - therapeutic use; Glycated Hemoglobin A - metabolism; Humans; Hypertension - complications; Hypoglycemic Agents - therapeutic use; Male; Middle Aged; Original Report: Patient-Oriented, Translational Research; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic - etiology; Renal Insufficiency, Chronic - metabolism; Severity of Illness Index; Thiophenes - therapeutic use; Treatment Outcome; Hypertension; Nephropathy; Diabetes; Kidney
• ISSN: 0250-8095; 1421-9670; 1421-9670
• DOI: 10.1159/000364909

Background/Aims: Some sodium glucose co-transporter 2 (SGLT2) inhibitors are approved for the treatment of patients with type 2 diabetes mellitus (T2DM) with an estimated glomerular filtration rate (eGFR) of ≥45 ml/min/1.73 m 2 . The efficacy and safety of canagliflozin, an approved SGLT2 inhibitor, was evaluated in patients with stage 3 chronic kidney disease (CKD; eGFR ≥30 to <60 ml/min/1.73 m 2 ). Methods: This analysis used integrated data from four randomized, placebo-controlled, phase 3 studies that enrolled patients with T2DM and stage 3 CKD. Results are presented for the overall population as well as subgroups with stage 3a CKD (eGFR ≥45 and <60 ml/min/1.73 m 2 ) and stage 3b CKD (eGFR ≥30 and <45 ml/min/1.73 m 2 ). Results: Among all subjects studied with stage 3 CKD, placebo-subtracted reductions in HbA 1c (-0.38 and -0.47%; p < 0.001), body weight (-1.6 and -1.9%; p < 0.001), and systolic blood pressure (-2.8 and -4.4 mm Hg; p < 0.01) were seen with canagliflozin 100 and 300 mg, respectively. Decreases in HbA 1c , body weight, and systolic blood pressure were examined in the stage 3a and 3b CKD subgroups, with greater decreases in HbA 1c , -0.47% (-0.61, -0.32) and body weight in subjects in stage 3a CKD, -1.8% (-2.3, -1.2) with canagliflozin 100 mg. Initial declines in eGFR were seen early following treatment initiation with canagliflozin, but trended towards baseline over time. The most common adverse events with canagliflozin included genital mycotic infections and adverse events related to reduced intravascular volume likely secondary to osmotic diuresis. Conclusion: In subjects with T2DM and stage 3 CKD, canagliflozin reduced HbA 1c , body weight, and blood pressure, and was generally well tolerated.