Will a Combination Drug Revolutionize Diabetes Therapy?Saturday, March 28, 2015
Glyxambi (empagliflozin/linagliptin) tablets, from Boehringer Ingelheim Pharmaceuticals, Inc. and Eli Lilly and Company was recently approved by the FDA, as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes (T2D). Glyxambi is the first diabetes drug in the U.S. to combine the dual mechanisms of action of a sodium glucose co-transporter-2 (SGLT2) inhibitor and a dipeptidyl peptidase-4 (DPP-4) inhibitor in a once-daily tablet.
SGLT2 inhibitors work in the kidneys to remove glucose through the urine by blocking blood glucose re-absorption in the kidney. DPP-4 inhibitors work by increasing hormones that stimulate the pancreas to produce more insulin and stimulate the liver to produce less glucose. Glyxambi is marketed as a combination of 10 mg or 25 mg of empagliflozin with 5 mg of linagliptin.
Glyxambi carries the warning and contraindications of both component medications. Contraindications include patients with severe renal impairment, end-stage renal disease, or dialysis. In addition, a history of hypersensitivity reaction to linagliptin, such as anaphylaxis, angioedema, exfoliative skin conditions, urticaria, or bronchial hyper reactivity is also considered a contraindication. There have been post-marketing reports of acute pancreatitis, including fatal pancreatitis, in patients taking linagliptin, a component of Glyxambi. Providers are encouraged to monitor patients taking the combination medication product for signs and symptoms of pancreatitis.
Glyxambi was compared in clinical trials against the components of the medication, empagliflozin (10 mg or 25 mg) and linagliptin (5 mg) in adults with T2D who were also taking high-dose metformin (mean dose 1889 mg daily).
The following results were reported at 24 weeks:
- Glyxambi showed statistically significant reductions in A1C compared with empagliflozin 10 mg, empagliflozin 25 mg and linagliptin 5 mg
- Higher percentage of patients achieved A1C <7% with Glyxambi 10/5 mg or 25/5 mg compared with empagliflozin 10 mg, empagliflozin 25 mg and linagliptin 5 mg
- Glyxambi at 10/5mg dose and 25/5 mg dose provided significant weight loss compared with linagliptin alone.
During the clinical trials, the overall incidence of hypoglycemia with Glyxambi were low, and there were no cases of severe hypoglycemia reported in the trial.
Adverse effects reported during the clinical trials:
- Urinary tract infection (UTI)
- Upper respiratory tract infection
Many patients with type 2 diabetes do not achieve recommended blood sugar control, making new treatment options more important than ever. Also, the more medications a patient has the more non-compliant the patient will be. This new combination medication product has the potential of increasing compliance with medication regimen because it combines 2 formulations in one medication product.
One concern that I believe should be addressed is the risk for hypoglycemia if Glyxambi is combined with insulin or a secretagouge like sulfonylurea. A lower dose of a secretagogue or insulin may be required to reduce the risk of hypoglycemia when used in combination with Glyxambi. Overall, I believe that Glyxambi is a great addition to the armament of diabetes medication therapy. It provides patients with less pill burden, and with closer monitoring to prevent hypoglycemia, Glyxambi can assist in bringing glucose levels under control.