Combined canagliflozin, metformin may offer better glycemic control than monotherapy, study finds

The industry-funded, double-blind, randomized, controlled trial assigned adult patients with type 2 diabetes who were not taking antihyperglycemic agents before the study to 26 weeks of treatment in 1 of 5 arms.


Initial combination therapy of canagliflozin 100 mg or 300 mg plus metformin extended-release may produce better glycemic improvements than either drug alone in drug-naive patients with type 2 diabetes, according to a new study.

Researchers conducted the double-blind trial from May 2013 to December 2014 at 158 centers in 12 countries. Results were published online Jan. 19 by Diabetes Care. Janssen Pharmaceuticals, Inc. manufactures the drugs used in this study, which was funded by Janssen Research & Development, LLC.

Adult patients with type 2 diabetes who were not taking antihyperglycemic agents prior to the study were randomized to 26 weeks of treatment in 5 arms: canagliflozin 100 mg/metformin extended-release; canagliflozin 300 mg/metformin extended-release; canagliflozin 100 mg; canagliflozin 300 mg; or metformin extended-release. Participants' mean baseline HbA1c was 8.8%.

Of 1,186 randomized patients, 1,069 (90.1%) completed 26 weeks of treatment. The primary efficacy end point was the change in HbA1c from baseline to week 26. Secondary end points included the proportion of patients who achieved an HbA1c of <7.0% and percent change from baseline in body weight.

All treatment arms achieved reductions in HbA1c, with the canagliflozin 100 mg/metformin and canagliflozin 300 mg/metformin groups producing larger reductions (−1.77% and −1.78%, respectively). The canagliflozin 100 mg, canagliflozin 300 mg, and metformin groups achieved reductions in HbA1c of −1.37%, −1.42%, and −1.30%, respectively. In this order, final mean HbA1c values were 7.0%, 7.0%, 7.4%, 7.3%, and 7.4%.

In the canagliflozin 100 mg/metformin and canagliflozin 300 mg/metformin groups, 49.6% and 56.8% of patients achieved HbA1c values of less than 7.0% at 26 weeks, compared to 38.8%, 42.8%, and 43.0% of patients in the canagliflozin 100 mg, canagliflozin 300 mg, and metformin groups, respectively. Also, in this order, percent weight loss from baseline across groups was −3.5%, −4.2%, −3.0%, −3.9%, and −2.1%.

Overall, the tolerability profile for the combination therapies was consistent with that of the respective monotherapies. Incidence of genital mycotic infections was higher in the canagliflozin arms, occurring in less than 4.4% in women and less than or equal to 4.0% of men compared with 0% of the metformin group. All genital mycotic infections were reported as mild or moderate in intensity. The incidence of serious adverse events was low across groups (≤3.0%), and the most commonly reported adverse event was diarrhea, with the highest incidence seen in the combination groups.

Compared to metformin, canagliflozin demonstrated noninferiority in HbA1c-lowering capabilities, as well as greater reductions in body weight. This suggests that canagliflozin may be an alternative to standard first-line antihyperglycemic therapy in newly diagnosed patients with type 2 diabetes, especially in those who cannot tolerate metformin, study authors noted.