In a Phase 3 study presented at the 48th European Association for the Study of Diabetes ( EASD ) Annual Meeting, Canagliflozin significantly reduced A1C levels compared to placebo, when added to ongoing antihyperglycemic therapy in older patients with type 2 diabetes not having adequate glycemic control.

In this 26-week randomized, double-blind, placebo-controlled study known as DIA3010, 714 patients with a mean age of 63.6 years were given once-daily doses of Canagliflozin ( 100 mg or 300 mg ), or placebo. Patients treated with Canagliflozin 100 mg and 300 mg doses had substantial and sustained decreases in A1C levels, and a significantly greater reduction relative to placebo after 26 weeks ( -0.57 and -0.70%, respectively, p less than 0.001 ). The overall incidence of treatment-emergent adverse effects was similar with both Canagliflozin 100 mg and 300 mg doses and placebo ( 71.8 and 78.0% vs. 73.4%, respectively ).

In secondary efficacy endpoint measures from DIA3010, patients treated with Canagliflozin 100 mg and 300 mg also had greater weight loss compared to placebo ( -2.3 and -3.0%, respectively, p less than 0.001); reductions in fasting plasma glucose, relative to placebo, were consistent with the primary A1C endpoint ( -1.4 and -1.5 mmol/L, respectively, p less than 0.001 ); systolic blood pressure was reduced with Canagliflozin 100 mg and 300 mg compared to placebo ( -4.6 and -7.9 mmHg, respectively, p less than 0.001 ). Canagliflozin 100 mg and 300 mg raised HDL-C relative to placebo [ 5.3% ( 0.06 mmol/L ) and 4.7% ( 0.05 mmol/L ), respectively, p less than 0.001 ) ], and LDL-C [ 7.5% ( 0.13 mmol/L ) and 7.8% ( 0.18 mmol/L ), respectively ]; reductions in diastolic blood pressure with Canagliflozin 100 mg and 300 mg ( -1.6 and -3.2 mmHg, respectively ); decreased triglycerides with Canagliflozin 100 mg ( -4.8% ) and increased triglyceride levels in patients receiving Canagliflozin 300 mg ( 0.7% ).

There were low rates of serious adverse effects ( 4.1 and 3.4% for Canagliflozin 100 mg and 300 mg vs 5.1% for placebo ) and adverse effct-related discontinuations ( 2.1 and 7.2% for Canagliflozin 100 mg and 300 mg vs 4.2% for placebo ) across groups.
Adverse events related to genital mycotic infections in men and women, osmotic diuresis-related events such as increased urination, and urinary tract infections were more frequent in patients treated with Canagliflozin than placebo. These specific adverse events were generally mild or moderate in intensity and infrequently led to discontinuation. Overall, 74.1% of patients were on a background antihyperglycemic therapy that can lead to hypoglycemia ( e.g. insulin and non–glucose-dependent insulin secretagogues ); in those patients, hypoglycemia rates were somewhat higher with Canagliflozin 100 mg and 300 mg than placebo ( 43.1 and 47.4% vs 37.7%, respectively ). In patients not on such agents the incidence of hypoglycemia episodes was low, with slightly higher rates observed for Canagliflozin 100 mg and 300 mg compared to placebo ( 6.7 and 4.8%,vs 3.2%, respectively ); one patient in the Canagliflozin 100 mg group experienced a severe hypoglycemia episode ( 1.7% ).

Canagliflozin is an investigational sodium glucose co-transporter 2 ( SGLT2 ) inhibitor for the treatment of patients with type 2 diabetes. The kidneys of people with type 2 diabetes reabsorb greater amounts of glucose back into the body compared to non-diabetic people, which may contribute to elevated glucose levels. Canagliflozin blocks the reabsorption of glucose by the kidney, increasing glucose excretion and lowering blood glucose levels.

Source: Janssen Research & Development, 2012

XagenaMedicine2012