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11-04-2013 | Endocrinology | Article

Canagliflozin outperforms sitagliptin as add-on in triple combination therapy


Free abstract

medwireNews: Canagliflozin may improve glycemic control and body weight reduction over sitagliptin in patients with Type 2 diabetes inadequately controlled with metformin plus sulfonylurea, indicate the results of a randomized double-blind trial.

The addition of canagliflozin significantly reduced glycated hemoglobin (HbA1c) levels compared with sitagliptin after a 52-week treatment period, report Guntram Schernthaner (Rudolfstiftung Hospital-Vienna, Austria) and colleagues. The drug also provided a significant and clinically relevant reduction in participants' body weight, whereas a slight weight increase was observed with sitagliptin.

Canagliflozin, which is an inhibitor of sodium/glucose cotransporter 2, lowers the renal threshold for glucose and substantially increases urinary glucose excretion (UGE), thereby reducing blood glucose levels, explains the team. This novel, insulin-independent approach is associated with caloric loss and low hypoglycemia risk, and potentially provides a mechanistic action that compliments that of other antidiabetes therapies.

The current trial was conducted at 140 centers in 17 countries, and included 755 patients inadequately controlled with metformin plus sulfonylurea, who were randomly allocated to receive daily canagliflozin 300 mg or daily sitagliptin 100 mg. Of the participants, 464 (61%) completed the 52-week treatment period.

As reported in Diabetes Care, canagliflozin was superior to sitagliptin in reducing HbA1c, at respective reductions of 1.03% and 0.66%.

In addition, a significantly greater proportion of individuals on canagliflozin achieved an HbA1c level below 7.0% compared with sitagliptin, at 47.6% versus 35.3%. Similarly, the proportion achieving an HbA1c level below 6.5% with canagliflozin versus sitagliptin was greater, at 22.5% versus 18.9%.

Canagliflozin also resulted in significantly greater reductions in body weight and blood pressure than sitagliptin, at -2.3 kg versus 0.1 kg and -5.1 mmHg versus 0.9 mmHg, respectively.

"The effect of canagliflozin on body weight is likely attributable to the marked increase in UGE, because each gram of glucose lost equates to the loss of 4 kcal," note the researchers.

The overall incidence of adverse events was similar between the canagliflozin and sitagliptin groups at 76.7% and 77.5%, respectively, and the rate of discontinuation due to adverse events was low in both groups, at 5.3% and 2.9%, respectively. The proportion of patients who had at least one hypoglycemic event was similar between the groups, as was the incidence of severe hypoglycemic episodes.

"These results support the potential value of canagliflozin in triple combination therapy with metformin plus a sulfonylurea for the treatment of patients with type 2 diabetes," concludes the team.

medwireNews ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013

By Sally Robertson, medwireNews Reporter

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