Fixed-dose combinations in type 2 diabetes – role of the canagliflozin metformin combination

Canagliflozin–metformin is one of the newest combination therapies available for the treatment of type 2 diabetes mellitus (T2DM). Canagliflozin is an inhibitor of the sodium–glucose co-transporter 2 which causes an increase in the urinary excretion of glucose. In the present article, we review the safety and efficacy of canagliflozin and metformin from data obtained from Phase III metformin add-on therapy clinical trials as there are no studies to date that specifically evaluate the combination of metformin and canagliflozin. Trials included in this review were dual-therapy trials of subjects who were already taking background metformin and were assigned to receive canagliflozin, glimepiride, or sitagliptin. The addition of canagliflozin to metformin resulted in a decrease in HbA(1c) of 0.73%–0.93%. Canagliflozin 100 mg was considered to be non-inferior to glimepiride and sitagliptin 100 mg with the canagliflozin 300 mg dose being statistically superior to sitagliptin and glimepiride. Other advantages of the use of canagliflozin are reduction in weight (3.3–4.0 kg) and systolic blood pressure (3.3–4.7 mmHg). The primary disadvantages are potential genital mycotic infections, hypotension, and gastrointestinal side effects from metformin. All things considered, this combination appears to be safe and effective in clinical trials and represents a promising option for the treatment of T2DM.