Canagliflozin an effective add-on for glycemic control
MedWire News: Canagliflozin is an effective new add-on regimen for the treatment of hyperglycemia, show findings from a US study.
Use of the add-on therapy significantly improved glycemic control in patients with diabetes inadequately controlled by metformin and was also associated with weight loss and low hypoglycemic risk, report Julio Rosenstock (Medical City Dallas Hospital, Texas) and colleagues.
Canagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is currently under development for the treatment of diabetes and has been shown to reduce the renal threshold for glucose reabsorption, increase urinary glucose excretion, reduce plasma glucose, and lead to weight loss.
In the current study, Rosenstock and team determined the dose-response efficacy and safety of canagliflozin in 451 diabetes patients with inadequate glycemic control (glycated hemoglobin [HbA1c] ≥7.0% to ≤10.5%) after at least 3 months of metformin (≥1500 mg/day) therapy.
Patients were randomly allocated to receive one of five canagliflozin doses (50, 100, 200, or 300 mg once daily or 300 mg twice daily), sitagliptin 100 mg once daily, or placebo for a period of 12 weeks.
"Sitagliptin was included as an active reference treatment group to provide clinical perspective," explain Rosenstock and colleagues.
The team assessed changes in mean HbA1c across the groups from baseline to the end of treatment.
As reported in Diabetes Care, there was a significantly greater reduction from baseline in mean HbA1c in all canagliflozin groups than in the placebo group. The mean HbA1c reduced by 0.79, 0.76, 0.70, 0.92, and 0.95% with canagliflozin 50, 100, 200, 300 mg once daily, and 300 mg twice daily, respectively, compared with a reduction of 0.22% with placebo. The reduction with sitagliptin was 0.74% which was not significantly different to the reductions observed with canagliflozin.
In addition, at least 5% body weight loss occurred significantly more frequently in the canagliflozin groups than in the placebo and sitagliptin groups, at rates of 16 to 32% versus 5% and 6%, respectively.
The incidence of adverse events and serious adverse events was generally low and similar across treatment groups, apart from the incidence of genital infections, which was reported by 13-25% of females in the canagliflozin groups, compared with 3% and 7% of those in the placebo and sitagliptin groups, respectively. The authors say that this is probably due to greater colonization of the vagina with Candida species with increased urinary glucose excretion.
"Future long-term studies examining the efficacy of canagliflozin with other antihyperglycemic medications will be needed," remark Rosenstock et al.
"However, the unique and distinct mechanism of glucose lowering with canagliflozin suggests that combination efficacy may be observed when this agent is added to other classes of agents," they conclude.
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By Sally Robertson