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FDA Approves Invokamet (Canagliflozin / Metformin) for Diabetes Patients

Combo therapy has twice-daily dosing

The FDA has approved Invokamet (Janssen Pharmaceuticals), a fixed-dose therapy combining canagliflozin and metformin hydrochloride in a single tablet, for the treatment of adults with type-2 diabetes.

Invokamet offers the clinical attributes of Invokana (canagliflozin, Janssen), the first sodium glucose co-transporter 2 (SGLT2) inhibitor available in the U.S., together with those of metformin, which is commonly prescribed early in the treatment of type-2 diabetes. Invokamet is the first fixed-dose combination of an SGLT2 inhibitor with metformin to be approved in the U.S.

Invokamet is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type-2 diabetes mellitus who are not adequately controlled by treatment that includes either canagliflozin or metformin, or who are already being treated with both canagliflozin and metformin as separate medications. Invokamet should not be used in patients with type-1 diabetes or diabetic ketoacidosis, and it is not known whether the treatment is safe and effective in children under 18 years of age.

Study results have demonstrated that the administration of Invokamet was equivalent to the co-administration of corresponding doses of canagliflozin and metformin as individual tablets.

Invokamet will be available in tablets containing canagliflozin 50 mg or 150 mg, and metformin 500 mg or 1,000 mg. The recommended dosing is twice daily. The prescribing information for Invokamet contains a boxed warning regarding the potential for lactic acidosis, a rare but serious complication caused by the accumulation of metformin.

The co-administration of canagliflozin and metformin as individual agents was evaluated in six phase III clinical studies that enrolled a total of 4,732 patients with type-2 diabetes. These studies evaluated canagliflozin/metformin compared with metformin alone or with metformin plus another diabetes therapy. The studies were part of the comprehensive global phase III program for Invokana that enrolled 10,285 patients, one of the largest clinical programs in type-2 diabetes submitted to health authorities to date. The phase III studies showed that the combination of canagliflozin and metformin lowered blood sugar and, in pre-specified secondary endpoints, was associated with significant reductions in body weight and systolic blood pressure.

In two studies comparing canagliflozin plus metformin versus current standard treatments plus metformin — one studying sitagliptin and the other studying glimepiride — canagliflozin dosed at 300 mg provided greater reductions in hemoglobin A1c (HbA1c) levels and body weight than did either comparator. HbA1c is the percent of red blood cell hemoglobin with glucose attached to it and is an indicator of average blood glucose over the previous 2 to 3 months.

The most common adverse events with canagliflozin were female genital fungal infections, urinary tract infections, and increased urination. These adverse events were generally mild-to-moderate in severity and rarely led to discontinuation in phase III studies. The most common adverse reactions due to the initiation of metformin included diarrhea, nausea/vomiting, flatulence, asthenia, indigestion, abdominal discomfort, and headache.

Hypoglycemia does not occur in patients receiving metformin alone under usual circumstances of use. Canagliflozin can increase the risk of hypoglycemia when combined with insulin or with a medication that increases insulin levels, such as a sulfonylurea. Therefore, a lower dose of insulin or an insulin-increasing medication may be required to minimize the risk of hypoglycemia when used in combination with canagliflozin.

Source: Janssen Pharmaceuticals; August 8, 2014.

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