Xigduo

Xigduo is indicated for adults aged 18 years and older with type 2 diabetes mellitus. It serves as an adjunct to diet and exercise to improve glycaemic control in patients inadequately controlled on metformin alone or in combination with other glucose-lowering medicinal products, including insulin, or for those already being treated with dapagliflozin and metformin as separate tablets. The legal basis for the application was Article 10(b) of Directive 2001/83/EC, and the product was not licensed in any country at the time of submission. The CHMP issued a positive opinion on 21 November 2013.

Efficacy studies demonstrated that Dapagliflozin AUC0-t (Test) was 104 ± 23.5 ng*h/ml compared to Dapagliflozin AUC0-t (Reference) of 103 ± 23.9 ng*h/ml. The Dapagliflozin AUC0-t Ratio (90% CI) was 1.02 (0.998-1.04). Metformin AUC0-t (Test) was 8270 ± 1571 ng*h/ml compared to Metformin AUC0-t (Reference) of 8320 ± 1569 ng*h/ml, with a Metformin AUC0-t Ratio (90% CI) of 1.00 (0.973-1.03).

Safety findings include a Metformin contraindication for renal dysfunction at < 60 ml/min. The Dapagliflozin starting dose for severe hepatic impairment is 5 mg. Dapagliflozin AUC exposure multiple at NOAEL relative to MRHD was 52 ×, while Metformin AUC exposure multiple at NOAEL relative to MRHD was 1.4 ×.