Patients with type 2 diabetes who are at elevated risk for cardiovascular disease experienced significant reductions in blood glucose when using canagliflozin as add-on therapy to treatment with insulin, new data indicate.
The Canagliflozin Cardiovascular Assessment Study (CANVAS) is a prospective, double blind, placebo-controlled trial designed to evaluate the efficacy, tolerability and CV safety of canagliflozin (Janssen Research & Development LLC) in 4,330 adults with type 2 diabetes who are considered to be at elevated risk for CVD. In the trial, researchers randomly assigned patients to once-daily canagliflozin 100 mg, 300 mg or placebo, besides stable ongoing diabetes therapy.
The 18-week substudy included 1,718 patients enrolled in CANVAS who were receiving insulin for an average of 7.1 years. Results revealed statistically greater reductions in HbA1c at 18 weeks in those assigned canagliflozin 100 mg (–0.65%) and 300 mg (–0.73%) vs. placebo (P<.001).
Patients in the canagliflozin 100-mg and 300-mg groups also experienced reductions in body weight of –1.9% and –2.4%, respectively, when compared with placebo (P<.001) and decreases in fasting plasma glucose of –1.25 mmol/L and –1.61 mmol/L, respectively (P<.001), according to a press release.
Additionally, compared with placebo, add-on therapy with canagliflozin 100 mg and 300 mg led to reductions in systolic (–2.6 mm Hg and –4.4 mm Hg; P<.001) and diastolic BP (–1 mm Hg and –1.8 mm Hg). Patients also experienced increases of 0.8% (P=.46) and 4.7% (P<.001) in HDL cholesterol, although this change was not statistically significant for the 100-mg dose. LDL rose by 6.3% and 6.6%, and total cholesterol increased by 1% and 3.3% with canagliflozin 100 mg and 300 mg. Changes in triglycerides were not statistically significant.
Incidence of adverse events leading to discontinuation was greater with canagliflozin 300 mg (5.3%) vs. canagliflozin 100 mg (1.9%) or placebo (1.9%). Most events were determined to be mild or moderate, according to the release. Genital mycotic infections, increased urination and hypotension were more common in the treatment groups when compared with placebo. Incidence of hypoglycemia was also higher with canagliflozin 100 mg and 300 mg vs. placebo (49% and 48% vs. 37%).
“Adults with type 2 diabetes are two to four times more likely to have heart disease or stroke compared to those who don’t have diabetes,” David R. Matthews, FRCP, professor of diabetes at the Oxford Centre for Diabetes, Endocrinology and Metabolism and co-lead investigator of the CANVAS trial, said in a press release. “Effective management of type 2 diabetes in patients with elevated CV risk and other comorbidities can be challenging because these patients are often more susceptible to complications of the side effects of antihyperglycemic therapy. The results from this substudy suggest that canagliflozin could provide an important new treatment option for higher-risk adult patients with type 2 diabetes.”
For more information:
Matthews DR. #764. Presented at: the 48th European Association for the Study of Diabetes Annual Meeting; Oct. 1-5, 2012; Berlin.
Disclosure: This study was supported by Janssen Research & Development LLC.