Fixed-dose tablet is the first sodium glucose cotransporter 2 (SGLT2) inhibitor plus metformin combo product to receive approval in the US.
Janssen Pharmaceuticals Inc. announced today that the US Food and Drug Administration (FDA) has approved Invokamet (canagliflozin/metformin HCl) for the treatment of adults with type 2 diabetes mellitus.
Invokamet is a fixed-dose combination of the sodium glucose cotransporter 2 (SGLT2) inhibitor canagliflozin and metformin. It will be available in tablets containing canagliflozin 50 mg or 150 mg, and metformin 500 mg or 1000 mg. The recommended dosing is twice daily.
Jimmy Ren, PhD, Therapeutic Area Lead, Metabolics, Medical Affairs, Janssen Pharmaceuticals, Inc. said in a statement that “Invokamet provides adults with type 2 diabetes an oral therapy that lowers blood sugar and is also associated with reductions in body weight and systolic blood pressure… The available doses of Invokamet allow physicians to tailor therapy for individual patient needs and offer an alternative for patients who may be able to reduce the number of tablets they take each day.”
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.
The drug should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.
Combination treatment with canagliflozin and metformin was studied in 6 Phase 3 clinical trials that enrolled 4,732 patients with type 2 diabetes. The studies evaluated canagliflozin in combination with metformin compared to metformin alone or to metformin plus another diabetes therapy. The trials 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,” according to the statement from Janssen.
In 2 studies comparing canagliflozin plus metformin to current standard diabetes treatments (sitagliptin in 1 study, glimepiride in the other) plus metformin, canagliflozin dosed at 300 mg “provided greater reductions in A1C levels and body weight than either comparator. In the studies, the overall incidence of adverse events was similar with canagliflozin and the comparators.”
The most common adverse events observed in trials with canagliflozin are female genital mycotic (fungal) infections, urinary tract infections, and increased urination. According to Janssen, “these specific adverse events were generally mild to moderate in intensity and infrequently led to discontinuation in Phase 3 studies.”
The prescribing information for metformin notes that the most common adverse reactions due to initiation of the medication are diarrhea, nausea/vomiting, flatulence, asthenia, indigestion, abdominal discomfort, and headache.
The statement from Janssen also noted that “hypoglycemia does not occur in patients receiving metformin alone under usual circumstances of use,” and that canagliflozin (marketed as Invokana by Janssen) “can increase the risk of hypoglycemia when combined with insulin or a medication that increases insulin levels,” such as a sulfonylurea.
Janssen warns that “a lower dose of insulin or insulin-raising medication may be required to minimize the risk of hypoglycemia when used in combination with Invokamet.”