Glyxambi Approved as First Dual SGLT2 and DDP-4 Inhibitor for Type 2 Diabetes

Commentary by: J. Michael Gonzalez-Campoy, MD, PhD, FACE

Glyxambi is now approved as an adjunct to nutrition and physical activity for the treatment of adults with type 2 diabetes mellitus. Glyxambi, from Boehringer Ingelheim Pharmaceuticals and Eli Lilly and Company, is the first diabetes treatment in the United States to combine the dual mechanisms of action of a sodium glucose co-transporter-2 (SGLT2) inhibitor and a dipeptidyl peptidase-4 (DPP-4) inhibitor. The medication is a once-daily tablet taken in the morning.
Cropped image of male doctor with prescription medicine bottle in clinic
"Both of these classes of medications are safe and effective to lower the blood glucose, each through a different mechanism of action," said J. Michael Gonzalez-Campoy, MD, PhD, FACE, Medical Director and Chief Executive Officer of the Minnesota Center for Obesity, Metabolism and Endocrinology in Eagan, Minnesota. "The potential side effects are those of the individual components, but it is important to note that hypoglycemia is NOT one of them. However, should Glyxambi be added to a sulfonylurea or to insulin, the risk of hypoglycemia does go up. Decreasing the doses of the sulfonylurea and/or insulin is advisable when starting Glyxambi," Dr. Gonzalez-Campoy said.

Empagliflozin is a SGLT2 inhibitor that blocks glucose from being reabsorbed in the kidneys. Linagliptin is a DPP-4 inhibitor that increases levels of incretin hormone levels, which stimulates the release of insulin, decreases glucagon levels, delays gastric emptying, and causes early satiety. Glyxambi is available in doses of either 10 mg or 25 mg of empagliflozin plus 5 mg of linagliptin.

Glyxambi is More Effective Than Either Empagliflozin or Linagliptin Alone
Approval by the U.S. Food and Drug Administration is based on data from a phase III trial showing that Glyxambi given as an adjunct to metformin was superior in reducing hemoglobin A1c (A1c) levels when compared with either empagliflozin or linagliptin alone (P<0.001 for all comparisons; see Table). Efficacy was maintained through 52 weeks. The study involved 686 adults with type 2 diabetes who were inadequately controlled on metformin.

Table. Glyxambi Versus Empagliflozin and Linagliptin in the Treatment of Type 2 Diabetes (n=686)

"Any time combination therapy is used, it is superior to monotherapy," Dr. Gonzalez-Campoy commented. "Whenever two medications are combined into 1 pill, adherence improves, and usually the cost decreases," he said.

Weight Loss Benefit
Glyxambi also led to more weight loss than treatment with linagliptin alone. The average weight loss with Glyxambi ranged from 3.1% to 3.4% compared to 0.7% with linagliptin alone.

"Weight management is now a primary treatment target for endocrinologists," Dr. Gonzalez-Campoy commented. "Using medications that have a weight advantage, such as Glyxambi, is recommended over the use of medications associated with weight gain and hypoglycemia risk, such as sulfonyluresas and insulin," he added.

Side Effects
In clinical trials, the most common side effects of Glyxambi were urinary tract infections (11.4%-12.5%), stuffy or runny nose and sore throat (5.9%-6.6%), and upper respiratory tract infections (7.0%).

Glyxambi should not be taken by patients with severe renal impairment, end-stage renal disease or dialysis; a history of hypersensitivity reaction to linagliptin, such as anaphylaxis, angioedema, exfoliative skin conditions, urticaria, or bronchial hyperreactivity; or history of serious hypersensitivity reaction to empagliflozin.

Postmarketing reports of acute pancreatitis, including fatal pancreatitis, have occurred in patients taking linagliptin. Thus, treatment should be discontinued in patients who develop pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk for recurrent pancreatitis while using the Glyxambi because the combination treatment has not been studied in patients with a history of pancreatitis.

February 11, 2015

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