Janssen has announced that use of the investigational agent Canagliflozin substantially has lowered blood glucose levels when used as add-on therapy in patients on insulin therapy for type 2 diabetes and who are considered to be at greater risk for cardiovascular disease.
These results were presented at the 48th European Association for the Study of Diabetes ( EASD ) Annual Meeting.
CANVAS ( CANagliflozin cardioVascular Assessment Study ) is a prospective, double blind, placebo-controlled trial designed to evaluate the efficacy, tolerability and cardiovascular safety of Canagliflozin in 4,330 adult patients with type 2 diabetes considered at elevated risk for cardiovascular disease.
The data presented were from an 18-week sub-study of 1,718 patients enrolled in CANVAS who were receiving insulin for an average of 7.1 years. Patients in this sub-study who were randomized to treatment with daily Canagliflozin 100 mg or 300 mg, in addition to their usual insulin regimen, had statistically greater A1C reductions at 18 weeks relative to placebo ( percent change from baseline, -0.65 and -0.73%, respectively, p less than 0.001 ).
The overall incidence of treatment-emergent adverse events was generally similar across all treatment arms.
In secondary efficacy endpoint measures in the CANVAS study, both the Canagliflozin 100 mg and 300 mg dose groups provided reductions in body weight relative to placebo ( body weight percent change, -1.9 and -2.4%, respectively, p less than 0.001 ).
Reductions in fasting plasma glucose were consistent with the primary endpoint for Canagliflozin 100 mg and 300 mg relative to placebo ( -1.25 and -1.61 mmol/L, respectively, p less than 0.001 ).
The study also met secondary end points including the following ( for Canagliflozin relative to placebo ): reductions in systolic blood pressure with Canagliflozin 100 mg and 300 mg ( -2.6 and -4.4 mmHg, respectively, p less than 0.001 ); reductions in diastolic blood pressure with Canagliflozin 100 mg and 300 mg ( -1.0 and -1.8 mmHg, respectively ); high-density lipoprotein cholesterol ( HDL-C ) increased with both 100 mg and 300 mg doses of Canagliflozin relative to placebo, [ percent change, 0.8% ( 0.02 mmol/L ), p=0.46, and 4.7% ( 0.05 mmol/L ), p less than 0.001, respectively ] though the change was not statistically significant for the 100 mg dose; low-density lipoprotein cholesterol ( LDL-C ) rose with Canagliflozin 100 mg and 300 mg [ 6.3% ( 0.03 mmol/L ) and 6.6% ( 0.11 mmol/L ), respectively ); non statistically significant changes in triglycerides with Canagliflozin 100 mg and 300 mg [ 0.2% ( 0.01 mmol/L ), p=0.95, and -2.0% ( -0.04 mmol/L ), p=0.44, respectively ]; and increases in total cholesterol levels with Canagliflozin 100 mg and 300 mg [ 1.0% ( 0.05 mmol/L ) and 3.3% ( 0.14 mmol/L ), respectively ].
The incidence of adverse effects leading to discontinuation was greater with Canagliflozin 300 mg ( 5.3% ) compared to Canagliflozin 100 mg or placebo ( 1.9% for both ). Most adverse effects were assessed by the investigator as mild to moderate in intensity and the overall incidence of adverse effects was balanced across treatment arms.
Adverse events of genital mycotic infections in men and women, increased urination ( pollakiuria ), and hypotension were more common with Canagliflozin 100 mg and 300 mg compared to placebo in men and women; these specific adverse events were generally mild or moderate in intensity and infrequently led to discontinuation. A slightly higher incidence of urinary tract infections was seen with Canagliflozin 300 mg than 100 mg or placebo. The incidence of hypoglycemia was higher with Canagliflozin 100 mg and 300 mg than placebo ( 49 and 48% vs. 37%, respectively ).
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