• Renal Disease
• Diabetes Mellitus
• Diabetes & Endocrinology Clinical Trials Diabetes & Kidney Disease

• Renal Disease
• Diabetes Mellitus
• Diabetes & Endocrinology Clinical Trials
• Endocrinology
• Diabetes & Metabolic Syndrome
• Diabetes & Kidney Disease

The sodium glucose cotransporter-2 inhibitor canagliflozin reduces HbA1C level in patients with type 2 diabetes mellitus (T2DM) and stage 3 chronic kidney disease (CKD), an effect that is more pronounced with higher levels of estimated glomerular filtration rate (eGFR), according to the results of a pooled analysis. Gary Meininger, MD, Janssen Research and Development LLC, Raritan, New Jersey, USA, presented the results of this pooled analysis of four randomized, double-blind, placebo-controlled Phase 3 trials that compared canagliflozin with placebo in patients with inadequately controlled T2DM and stage 3 CKD.

Options for glycemic control in patients with T2DM and impaired renal function are limited, said Dr. Meininger. Canagliflozin has been approved in the United States as an adjunct to diet and exercise to improve glycemic control in adults with T2DM. However, its approved dosage is limited to 100 mg QD in patients with moderate renal impairment with an eGFR ≥45 and <60 mL/min/1.73 m², and it is not indicated in patients with an eGFR <45 mL/min/1.73 m².

The present pooled analysis included 1085 patients with T2DM and stage 3 CKD (eGFR ≥30 and <60 mL/min/1.73 m²) who were randomized to canagliflozin 100 or 300 mg, or placebo for 18 to 26 weeks.

In the overall study population, the mean change from baseline to efficacy assessment in HbA1C was −0.52% in the canagliflozin 100-mg group; −0.62% in the canagliflozin 300-mg group; and −0.14% in the placebo group (p<0.001 for both canagliflozin groups vs placebo). When assessed by baseline eGFR, a greater reduction in HbA1C with canagliflozin was observed in patients with eGFR ≥45 mL/min/1.73 m² and <60 mL/min/1.73 m² than in those with eGFR ≥30 and <45 mL/min/1.73 m².

In the 88.2% of all participants who were on background insulin or a sulfonylurea, the rates of documented episodes of hypoglycemia were greater with canagliflozin 100 mg and 300 mg (41.9% and 43.8%, respectively) than with placebo (29.2%).

Weight loss was also greater in the canagliflozin groups than in the placebo groups, and the effect was greater in patients with eGFR ≥45 mL/min/1.73 m² than in those with eGFR ≥30 and <45 mL/min/1.73 m².

Systolic blood pressure decreased more in the overall study population in the canagliflozin groups versus the placebo group. In the subgroup with eGFR ≥30 and <45 mL/min/1.73 m², systolic blood pressure increased by 0.8 mm Hg in each canagliflozin group and by 5.7 mm Hg in the placebo group.

The incidence of overall adverse events (AEs) was higher with canagliflozin (74.0% with 100 mg and 75.3% with 300 mg) than with placebo (70.4%). Intravascular volume-related adverse events were also more common with canagliflozin (5.0% and 8.5% in the 100- and 300-mg groups, respectively) than with placebo (2.6%). The percentage of these events in the canagliflozin groups was greater in patients with eGFR ≥30 and <45 mL/min/1.73 m² (6.6% and 11.1% in the 100- and 300-mg groups, respectively) relative to placebo (1.7%) than in those with eGFR ≥45 mL/min/1.73 m² (4.2% and 7.1% with 100-mg and 300-mg canagliflozin, respectively, vs 3.0% with placebo). Renal-related adverse events also occurred more frequently with canagliflozin compared with placebo, and the rates were higher in all three groups with eGFR ≥30 and <45 mL/min/1.73 m².

• © 2013 MD Conference Express®