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

Abstract

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 m². 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 m²). 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 m²) and stage 3b CKD (eGFR ≥30 and <45 ml/min/1.73 m²). 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 subjectswith T2DM and stage 3 CKD, canagliflozin reduced HbA_1c, body weight, and blood pressure, and was generally well tolerated.

Effect of Sodium‐Glucose Cotransport‐2 Inhibitors on Blood Pressure in People With Type 2 Diabetes Mellitus: A Systematic Review and Meta‐Analysis of 43 Randomized Control Trials With 22 528 Patients

“…Four studies had moderate risk of bias,13, 17, 26, 36 whereas other studies evaluated had a low risk of bias based on selective outcome reporting. Details of the quality of bias assessment are shown in Table S3.…”

“…Data were sorted by first author, year of publication, country of the study, design, age range of the participants, total sample size, SGLT2 inhibitor, comparator, number of patients, dosage, and follow‐up duration (Table 1). 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55 …”

Renal sodium-glucose cotransporter inhibition in the management of type 2 diabetes mellitus

“…To the contrary, a decrease in proteinuria has been reported with SGLT2 inhibitors in experimental animals (46,97) and humans (71,104), and the decrease was independent of lowering the plasma glucose concentration. Importantly, subjects with mutations in the SGLT2 gene maintain normal kidney function without proteinuria despite excreting large amounts of glucose (Ͼ50 -100 g/24 h) over a lifetime (85).…”

Successful Withdrawal from Dobutamine by Canagliflozin in a Diabetic Patient with Stage D Heart Failure

“…30 to < 60 mL/minute/1.73 m 2 ). 10,11) We confirmed marked glycosuria without hypoglycemia after the administration of the drug and considered that the efficacy and safety of the drug were undeniable in this patients with eGFR of 36.5 mL/minute/1.73 m 2 .…”