Combo SGLT2 Inhibitors Double Down on Diabetes

March 3, 2015

The use of SGLT2 inhibitors in combination with other agents to improve glycemic control has emerged as a promising therapeutic option.

If left uncontrolled, type 2 diabetes mellitus (T2DM) can result in serious complications. Improved glycemic control reduces their onset and progression, but close to half of adults who have T2DM do not achieve levels of glucose control recommended by the American Diabetes Association.

While the search goes on for novel therapeutic agents to improve glycemic control in patients with T2DM, the use of sodium glucose co-transporter-2 (SGLT2) inhibitors in combination with other agents has emerged as a promising treatment option.

Three combination SGLT2 products have been FDA-approved within the past 6 months. Find key points about each of these new agents on the pages that follow.

Click here for details on Glyxambi.

Glyxambi Is the Only SGLT2 and DPP-4 Combo

Glyxambi (empagliflozin and linagliptin), an SGLT2 inhibitor and dipeptidyl peptidase-4 (DPP-4) inhibitor combination for the treatment of adults with T2DM, was FDA-approved in February 2015.

• Glyxambi is currently the only prescription medication in the United States that combines the mechanisms of action of SGLT2 and DPP-4 inhibitors to improve glycemic control as an adjunct to diet and exercise.

• A phase 3 clinical trial evaluated the efficacy and safety of Glyxambi (10/5 mg and 25/5 mg) compared with the individual components (empagliflozin, 10 mg or 25 mg; linagliptin, 5 mg) in 686 adults with T2DM who were also taking high-dose metformin.

• As an add-on to metformin, Glyxambi showed statistically significant reductions in A1c level compared with empagliflozin and linagliptin alone at 24 weeks.

• Empagliflozin/linagliptin was well tolerated. The most common adverse effects include urinary tract infections, stuffy or runny nose and sore throat, and upper respiratory tract infections.

• Glyxambi is not recommended in patients with type 1 diabetes mellitus or those with diabetic ketoacidosis. It should not be taken by patients with severe renal impairment, end-stage renal disease, or dialysis or a history of hypersensitivity reaction to linagliptin or of serious hypersensitivity reaction to empagliflozin.

• Although Glyxambi is not approved for weight loss, it provided significant reduction in weight at 24 weeks compared with linagliptin alone.

Click here for details on Xigduo XR.

Dapagliflozin, Metformin Combined in Xigduo XR

Xigduo XR (dapagliflozin and metformin hydrochloride) extended release, a combination of an SGLT2 inhibitor and a biguanide for patients with T2DM, received FDA approval in October 2014.

• The FDA approved once-daily Xigduo XR based on 4 phase 3 clinical trials. The trials provided clinical evidence for efficacy and safety in treatment-naive patients and in patients inadequately controlled on metformin and compared with a sulfonylurea (glipizide) plus metformin.

• This is the first US approval for a once-daily tablet that combines an SGLT2 inhibitor and metformin HCl extended release-antihyperglycemic agents with complementary mechanisms of action.

• This combination is indicated as an adjunct therapy to diet and exercise to improve glycemic control in adults with T2DM when treatment with both dapagliflozin and metformin is appropriate.

• Xigduo XR was already approved in Australia for adults with T2DM, and Xigduo (dapagliflozin and metformin hydrochloride), which uses an immediate-release form of metformin, is approved in the European Union.

• Xigduo XR is approved with multiple dosage strengths of dapagliflozin and metformin HCl extended release, respectively, including 5 mg/500 mg, 5 mg/1000 mg, 10 mg/500 mg, and 10 mg/1000 mg.

• Xigduo XR should be taken once daily in the morning with food with gradual dose escalation to reduce the risk of GI adverse effects caused by metformin.

Click here for details on Invokamet.

Invokamet: An SGLT2 Inhibitor With Metformin

 Invokamet (canagliflozin and metformin hydrochloride) is an SGLT2 inhibitor and biguanide combination indicated as an adjunct to diet and exercise to improve glycemic control in adults with T2DM who are not adequately controlled on a regimen containing metformin or canagliflozin or in patients already being treated with both canagliflozin and metformin. The drug received FDA approval in August 2014.

• Invokamet is the first fixed-dose combination of an SGLT2 inhibitor with metformin approved in the United States.

• The co-administration of canagliflozin and metformin has been studied in 6 phase 3 clinical studies that enrolled 4732 patients who had T2DM. The studies evaluated canagliflozin in combination with metformin compared with metformin alone and with metformin plus another DM therapy.

• The combination lowered blood sugar and, in prespecified secondary end points, was associated with significant reductions in body weight and systolic blood pressure.

• Invokamet should not be used in patients with type 1 DM or for diabetic ketoacidosis. The prescribing information also contains a boxed warning for lactic acidosis.

• Potential serious adverse effects include dehydration, kidney problems, hyperkalemia, liver problems, and hypoglycemia.

• Invokamet is available in tablets containing canagliflozin, 50 mg or 150 mg, and metformin, 500 mg or 1000 mg. The recommended dosing is twice daily.

 

Take-aways:

• The use of SGLT2 inhibitors in combination with other agents has emerged as a promising therapeutic option for patients with T2DM.

• Glyxambi is the only prescription medication in the United States that combines SGLT2 and DPP-4 inhibitors to improve glycemic control as an adjunct to diet and exercise.

• The approval of Xigduo XR is the first in the United States for a once-daily tablet that combines an SGLT2 inhibitor and metformin HCl extended release.

• Invokamet is the first fixed-dose combination of an SGLT2 inhibitor with metformin approved in the United States.

Professional Prescribing Information:

Glyxambi http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing+Information/PIs/Glyxambi/Glyxambi.pdf

Xigduo XR http://www.azpicentral.com/xigduo/pi_xigduoxr.pdf

Invokamet http://www.janssenprescriptionassistance.com/invokamet-cost-assistance