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FDA Approves Invokamet XR for Treatment of Adults With Type-2 Diabetes
The FDA has approved Invokamet XR (Janssen Pharmaceuticals) for first-line use as an adjunct to diet and exercise to improve blood glucose control in adults with type-2 diabetes (T2D) when treatment with the two medications is appropriate.
Invokamet XR is a once-daily, fixed-dose combination of canagliflozin (Invokana), the most-prescribed sodium glucose co-transporter 2 (SGLT2) inhibitor, and an extended-release formulation of metformin, which is commonly prescribed as an initial therapy for the treatment of patients with T2D. Canagliflozin works with the kidneys to help adults with T2D lose some sugar through the process of urination, and metformin decreases the production of glucose in the liver and improves the body’s response to insulin.
Phase 3 studies have shown that the combination of canagliflozin and metformin reduces hemoglobin A1C (HbA1C) significantly more when compared with metformin monotherapy, sitagliptin plus metformin, or glimepiride plus metformin. Treatment with canagliflozin as an add-on to metformin also demonstrated greater reductions in the secondary endpoints of body weight and systolic blood pressure. HbA1C is a measure of average blood glucose during the past two to three months; the American Diabetes Association recommends that most adults with T2D maintain HbA1C levels of 7% or less.
Invokamet, the first combination of an SGLT2 inhibitor and an immediate-release formulation of metformin available in the United States, was initially approved by the FDA in August 2014 as an adjunct to diet and exercise to improve glycemic control in adults with T2D not adequately controlled with metformin or canagliflozin, or who are being treated with both medications separately. In May 2016, the FDA expanded the Invokamet indication to include adults with T2D who are not being treated with canagliflozin or metformin and may benefit from dual therapy.
The coadministration of canagliflozin and metformin has been evaluated in seven phase 3 studies. One study included 1,186 adults with T2D inadequately controlled with diet and exercise, and who had not been treated with glucose-lowering medications; the six other studies included 4,732 patients with T2D who were taking glucose-lowering medications. Collectively, the phase 3 trials showed that the combination of canagliflozin and metformin lowered blood sugar and was associated with greater reductions in body weight and systolic blood pressure.
The phase 3 studies also showed that canagliflozin is generally well tolerated. The most common adverse events included genital yeast infections, urinary tract infections, and changes in urination. The most common adverse reactions due to the initiation of metformin include diarrhea, nausea, vomiting, flatulence, asthenia, indigestion, abdominal discomfort, and headache.
Canagliflozin can increase the risk of hypoglycemia when it is combined with insulin or a medication that increases insulin levels, such as a sulfonylurea. Therefore, a lower dose of insulin or an insulin-raising medication may be required to minimize the risk of hypoglycemia when used in combination with Invokamet XR.
Invokamet XR is available in four dosages, in tablets containing canagliflozin 50 mg or 150 mg, and extended-release metformin 500 mg or 1,000 mg. The recommended dosage is two tablets once daily with the morning meal.
The prescribing information for Invokamet XR includes a boxed warning regarding lactic acidosis, a rare but serious complication that can occur because of metformin accumulation.
Source: Janssen; September 21, 2016.