Efficacy and safety of twice-daily treatment with canagliflozin, a sodium glucose co-transporter 2 inhibitor, added on to metformin monotherapy in patients with type 2 diabetes mellitus

• Canagliflozin BID was evaluated in patients with type 2 diabetes on metformin.
• Canagliflozin 50 and 150 mg BID significantly reduced HbA1c vs placebo.
• Both doses also lowered fasting plasma glucose, body weight, and blood pressure.
• Efficacy findings were consistent with studies of canagliflozin 100 and 300 mg QD.
• Canagliflozin BID was generally well tolerated, similar to canagliflozin QD.

AimTo evaluate the efficacy/safety of canagliflozin twice daily (BID) compared with placebo in patients with type 2 diabetes mellitus (T2DM) on metformin.MethodsIn this 18-week, randomized, double-blind, placebo-controlled study, patients (N = 279) at 60 centers in 7 countries received canagliflozin 50 or 150 mg or placebo BID. The pre-specified primary endpoint was change from baseline in HbA1c at Week 18. Pre-specified secondary endpoints included proportion of patients reaching HbA1c <7.0%, change in fasting plasma glucose (FPG), and percent change in body weight; changes in systolic blood pressure (BP) and fasting plasma lipids were also evaluated. Adverse events (AEs) were recorded throughout the study.ResultsFrom a mean baseline HbA1c of 7.6% (60 mmol/mol), canagliflozin 50 and 150 mg BID significantly reduced HbA1c compared with placebo at Week 18 (−0.45%, −0.61%, −0.01% [−5, −7, −0.1 mmol/mol], respectively; P < 0.001). More patients achieved HbA1c <7.0% with canagliflozin than placebo (P < 0.05). Relative to placebo, both canagliflozin doses significantly lowered FPG and body weight (P < 0.001), and reduced systolic BP. Overall AE incidence was 35.5%, 40.9%, and 36.6% with canagliflozin 50 and 150 mg BID and placebo, respectively. Canagliflozin was associated with increased incidences of urinary tract infections, female genital mycotic infections, and osmotic diuresis-related AEs; these led to few discontinuations. The incidence of documented hypoglycemia was low across groups.ConclusionsCanagliflozin 50 and 150 mg BID provided significant glycemic efficacy and body weight reduction, and were generally well tolerated in patients with T2DM on background metformin.ClinicalTrials.gov Identifier: NCT01340664