FDA Expands Invokamet Label to Include First-Line Treatment of Adults With Type-2 Diabetes

Product offers first combination of SGLT2 inhibitor and metformin

The FDA has approved Invokamet (Janssen), a fixed-dose combination therapy consisting of canagliflozin (Invokana) and metformin hydrochloride, for first-line treatment of adults with type-2 diabetes. With this new approval, Invokamet may now be prescribed in adults with type-2 diabetes who are not already being treated with canagliflozin or metformin and who may benefit from dual therapy.

Invokamet, the first combination of a sodium-glucose cotransporter 2 (SGLT2) inhibitor and metformin available in the United States, was originally approved by the FDA in August 2014 as an adjunct to diet and exercise to improve blood glucose control in adults with type-2 diabetes not adequately controlled by either canagliflozin or metformin, or who are already being treated with both medications separately.

The expanded indication was based largely on results from a 26-week, phase 3, double-blind, active-controlled study in 1,186 adults with type-2 diabetes whose disease was inadequately controlled with diet and exercise, and who had not been treated with any glucose-lowering medications. The subjects were randomly assigned to one of five treatment groups: metformin hydrochloride extended release (MET); canagliflozin 100 mg (CANA100); canagliflozin 300 mg (CANA300); canagliflozin 100 mg plus MET (CANA100/MET); or canagliflozin 300 mg plus MET (CANA300/MET). The study’s primary endpoint was the change in A1C (a measure of average blood glucose over the previous two or three months). The study findings were published in the March 2016 issue of Diabetes Care.

After 26 weeks of treatment, participants in the CANA100/MET and CANA300/MET groups showed significantly greater decreases in A1C compared with those in the CANA100, CANA300, and MET groups: 1.77% and 1.78% vs. 1.37%, 1.42%, and 1.30%, respectively (P < 0.001 for all differences between the combination therapies vs. individual therapies). In addition, significantly more participants in the CANA100/MET and CANA300/MET groups compared with the MET group achieved the goal of reducing A1C to less than 7%: 47% and 51% vs. 38%, respectively (P < 0.05 for both combination groups vs. MET).

Invokamet is available in four dose strengths in tablets containing canagliflozin 50 mg or 150 mg, and metformin 500 mg or 1,000 mg. The recommended dosage is twice daily. The prescribing information for Invokamet includes a boxed warning regarding the potential for lactic acidosis, a rare but serious complication that can occur due to metformin accumulation.

Source: Janssen; May 24, 2016.