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FDA Approves Empagliflozin/Linagliptin Combination Glyxambi

Feb 6, 2015

Approved as an adjunctive treatment to diet and exercise for adults with type 2 diabetes…

The once-daily tablet is the first in the United States to combine a sodium glucose cotransporter 2 (SGLT2) inhibitor (empagliflozin) with a dipeptidyl peptidase-4 (DPP-4) inhibitor (linagliptin). The tablets contain 10 or 25 mg of empagliflozin and 5 mg of linagliptin.

The product is not indicated for type 1 diabetes or those with pancreatitis.

The FDA approval was based on a phase 3 clinical trial comparing the combination of empagliflozin/linagliptin at both the 10/5 mg and 25/5 mg doses to the individual doses of both drugs. The study randomized 686 adults with type 2 diabetes who had baseline hemoglobin A1c (HbA1c) levels between 7.0% and 10.5% despite taking high-dose metformin (mean daily dose 1889 mg).

The phase 3 data were published online January 12, 2015 in Diabetes Care by Ralph A DeFronzo, MD of the University of Texas Health Science Center, San Antonio, and colleagues.

The results of the phase 3 trial showed that, at 24 weeks, those receiving empagliflozin/linagliptin achieved mean HbA1c levels of 6.9% with the 10/5 mg dose and 6.7% with the 25/5 mg dose, compared with 7.3% and 7.4% with empagliflozin 10 and 25 mg, respectively, and 7.3% with linagliptin 5 mg.

The proportions of patients who achieved HbA1c values less than 7% were 58% with the 10/5 mg combination dose and 62% with the 25/5 mg combination dose, compared with 28%, 33%, and 36% for empagliflozin 10 mg, empagliflozin 25 mg, and linagliptin 5 mg, respectively.

Patients taking the combination also lost slightly more than 3% of their body weight.

At 52 weeks, urinary tract infections (UTI) occurred in 12.5% of patients with the lower dose of empagliflozin and 11.4% with the higher dose, but no patients discontinued because of a UTI. Other common adverse events included nasopharyngitis (5.9% and 6.6%, respectively) and upper respiratory tract infection (7.0% for both doses).

However, study limitations “include the lack of a placebo arm, which means that the additive efficacy of empagliflozin/linagliptin compared with the individual components cannot be conclusively assessed, although only small changes from baseline in HbA1c with placebo would be expected,” Dr DeFronzo and colleagues conclude.

Andrew Lewin. Initial Combination of Empagliflozin and Linagliptin in Subjects With Type 2 Diabetes, Diabetes Care, Published online before print January 29, 2015, doi: 10.2337/dc14-2365