FDA approves first fixed-dose treatment for type 2 diabetes

FDA has approved canagliflozin/metformin (Invokamet, Janssen), the first fixed-dose combination in the class of sodium glucose co-transporter 2 (SGLT2) inhibitors for the treatment of adults with type 2 diabetes.

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

“This marks a meaningful advance for patients,” according to Marcia Rupnow, PhD, senior director, Health Economics & Outcomes Research (HECOR), Metabolics, Janssen Scientific Affairs.

“It combines the complementary clinical attributes of [canagliflozin], the first SGLT2 inhibitor available in the United States and now with over 16 months of real-world clinical experience, together with those of metformin, which is commonly prescribed early in the treatment of type 2 diabetes,” Rupnow said. “And since metformin is one of the most commonly prescribed antihyperglycemic agents, this combination helps patients simplify their medication management and harness the benefits of these 2 products with complementary mechanisms of action.”

In 2 studies comparing Invokana plus metformin to current standard treatments plus metformin-one studying sitagliptin and the other studying glimepiride- Invokana dosed at 300 mg provided greater reductions in A_1C levels and body weight than either comparator. In the 2 studies, the overall incidence of adverse events was similar with Invokana and the comparators.  

Results from the phase 3 studies showed that the most common adverse events with Invokana are female genital fungal infections, urinary tract infections and increased urination. These specific adverse events were generally mild to moderate in intensity and infrequently led to discontinuation in phase 3 studies. The most common adverse reactions due to initiation of metformin are diarrhea, nausea/vomiting, flatulence, asthenia, indigestion, abdominal discomfort, and headache. Hypoglycemia does not occur in patients receiving metformin alone under usual circumstances of use. Invokana can increase the risk of hypoglycemia when combined with insulin or a medication that increases insulin levels (eg, a sulfonylurea). Therefore, a lower dose of insulin or insulin-raising medication may be required to minimize the risk of hypoglycemia when used in combination with Invokamet.

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 also contains a boxed warning for lactic acidosis, a rare, but serious complication that can occur due to metformin accumulation.

In March 2013, FDA approved canagliflozin as a single agent.