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Data Show Improved HbA1c with Canagliflozin

Authors

Eileen Koutnik-Fotopoulos

San Francisco—Clinical trials of canagliflozin improved hemoglobin A1c (HbA1c) in patients with type 2 diabetes compared with sitagliptin, according to data from 2 studies presented at the ADA meeting during a product theater sponsored by Janssen Pharmaceuticals, Inc.

Canagliflozin is a sodium-glucose cotransporter-2 (SGLT-2) inhibitor. It is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. It is not recommended for the treatment of type 1 diabetes or diabetic ketoacidosis. The recommended starting dose of canagliflozin is 100 mg once daily. In patients tolerating canagliflozin 100 mg once daily who have an estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m2 and require additional glycemic control, the dose can be increased to 300 mg once daily. As an inhibitor of SGLT-2, canagliflozin reduces renal glucose reabsorption and increases urinary glucose excretion, explained Carol Wysham, MD, clinical associate professor of medicine, University of Washington, Spokane, Washington.

The safety and efficacy of canagliflozin have been evaluated as a monotherapy and in combination with other type 2 diabetes medications. Dr. Wysham discussed the results of 2 studies. The primary end point was change in HbA1c from baseline, and secondary end points were mean change in fasting plasma glucose (FPG) and reduction in body weight.

In study 1, treatment with canagliflozin 300 mg provided greater reductions in HbA1c compared with sitagliptin 100 mg at 52 weeks in a randomized, double-blind, active-controlled study of 755 patients inadequately controlled on metformin plus a sulfonylurea. Patients were randomized to receive canagliflozin 300 mg in combination with metformin plus a sulfonylurea (n=377) or sitagliptin 100 mg in combination with metformin plus a sulfonylurea (n=378). At the end of treatment, the canagliflozin cohort had an HbA1c change from baseline of -1.03% versus -0.66% for the sitagliptin cohort (-0.37 difference from sitagliptin; P<.05). Canagliflozin provided greater reductions in FPG and body weight compared with sitagliptin. Canagliflozin had an adjusted mean change in FPG from baseline of -30 mg/dL versus -6 mg/dL for sitagliptin. As for body weight, canagliflozin had an adjusted mean change in body weight from baseline of -2.5% compared to 0.3% for sitagliptin [Diabetes Care. 2013;36(9):2508-2515].

Study 2 assessed canagliflozin in a randomized, placebo-controlled, active-controlled study consisting of a 26-week placebo-controlled and active-controlled, double-blind treatment period followed by a 26-week active-controlled, double-blind treatment period in 1284 patients inadequately controlled on metformin alone. Patients were randomized to receive canagliflozin 100 mg (n=368), canagliflozin 300 mg (n=367), sitagliptin 100 mg (n=366), or placebo (n=183), all administered once daily in combination with metformin [Diabetologia. 2013;56(12):2582-2592].

At 26 weeks of treatment, the results showed that both canagliflozin treatment arms had greater reductions in HbA1c versus placebo. The adjusted mean change in HbA1c from baseline for canagliflozin 100 mg and 300 mg was -0.82% and -0.94%, respectively, versus -0.17% for the placebo group. Both canagliflozin 100 mg and 300 mg treatment arms also demonstrated similar and greater reductions in HbA1c versus sitagliptin 100 mg. The adjusted mean change in HbA1c from baseline was the same for the canagliflozin and sitagliptin 100 mg groups (-0.73%); however, canagliflozin 300 mg demonstrated a -0.88% change.

Canagliflozin 100 mg and 300 mg treatment arms also showed greater reductions in FPG versus sitagliptin 100 mg (-26 mg/dL and -35 mg/dL vs -18 mg/dL, respectively) and body weight versus sitagliptin 100 mg (-3.8% and -4.2 % vs -1.3%, respectively).

The incidence of hypoglycemia in study 1 was 43.2% for canagliflozin 300 mg and 40.7% for sitagliptin
100 mg. In study 2, there was no difference in the incidence of hypoglycemia for canagliflozin 100 mg and 300 mg (6.8%), but it was still higher than sitagliptin 100 mg (4.1%).—Eileen Koutnik-Fotopoulos

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