European Commission approves first oral therapy for type 1 diabetes

The European Commission this week approved the SGLT2 inhibitor dapagliflozin for use in type 1 diabetes as an adjunct to insulin in patients with a BMI of at least 27 kg/m², Astra Zeneca announced in a press release.

The European approval of dapagliflozin (Forxiga) marks the first approval of an oral type 1 diabetes therapy outside the United States. The medication is indicated for adults with type 1 diabetes with inadequate glycemic control despite optimal insulin therapy. Dapagliflozin is currently under regulatory review in the U.S. (as Farxiga) and Japan for use as an adjunct treatment to insulin in adults with type 1 diabetes, with decisions expected in the first and second half of 2019, respectively, according to the company.

“Forxiga is the first oral medicine approved in Europe as an adjunct to insulin for people living with type 1 diabetes whose glucose levels are not adequately controlled with insulin alone,” Elisabeth Björk, senior vice president, head of late cardiovascular, renal and metabolism, R&D BioPharmaceuticals, said in the release. “We look forward to bringing Forxiga to a patient population that has not had any approved oral medicines available before.”

The approval is based on data from the phase 3 DEPICT clinical program. The short-term (24-week) and long-term (52-week) data from DEPICT 1, along with the short-term data from DEPICT 2, demonstrated that 5 mg dapagliflozin daily, when given as an adjunct to adjustable insulin in patients with inadequately controlled type 1 diabetes, was associated with reductions from baseline in HbA1c (primary endpoint), weight and total daily insulin dose (secondary endpoints) at weeks 24 and 52, according to the release.

The safety profile of dapagliflozin in the type 1 diabetes studies was consistent with findings from the type 2 diabetes trials with the drug, apart from a higher number of observed cases of diabetic ketoacidosis (DKA) in patients who received dapagliflozin, according to the release.

Dapagliflozin is already indicated as a monotherapy and as part of combination therapy in adults with type 2 diabetes to improve glycemic control, with the additional benefits of weight loss and blood pressure reduction, as an adjunct to diet and exercise. In February, the FDA approved a label update for dapagliflozin, expanding its use for patients with type 2 diabetes and moderate renal impairment. As Endocrine Today previously reported, the expanded indication is intended for both dapagliflozin (Farxiga) and dapagliflozin plus metformin extended-release (Xigduo XL) and lowers the estimated glomerular filtration rate threshold to 45 mL/min/1.73m², indicating moderate chronic kidney disease, from 60 mL/min/1.73m².

In a meta-analysis published in January 2018 in Diabetes Research and Clinical Practice and reported by Endocrine Today, researchers found that combined treatment with SGLT2 inhibitors and insulin is a viable option for treating patients with type 1 diabetes. In an analysis of four randomized controlled trials of therapy with SGLT2 inhibitors, including dapagliflozin, researchers found that SGLT2 inhibitors lowered HbA1c and were associated with lower daily doses of insulin and lower body weight compared with placebo. However, the researchers acknowledged that the study was limited by its small sample size, as three of the four trials included fewer than 100 participants. Furthermore, the studies included in the analysis used varying lengths of treatment, including two that ran for less than 12 weeks. – by Regina Schaffer

Disclosures: Björk is senior vice president and head of late cardiovascular, renal and metabolism at R&D BioPharmaceuticals.

The European Commission this week approved the SGLT2 inhibitor dapagliflozin for use in type 1 diabetes as an adjunct to insulin in patients with a BMI of at least 27 kg/m², Astra Zeneca announced in a press release.

The European approval of dapagliflozin (Forxiga) marks the first approval of an oral type 1 diabetes therapy outside the United States. The medication is indicated for adults with type 1 diabetes with inadequate glycemic control despite optimal insulin therapy. Dapagliflozin is currently under regulatory review in the U.S. (as Farxiga) and Japan for use as an adjunct treatment to insulin in adults with type 1 diabetes, with decisions expected in the first and second half of 2019, respectively, according to the company.

“Forxiga is the first oral medicine approved in Europe as an adjunct to insulin for people living with type 1 diabetes whose glucose levels are not adequately controlled with insulin alone,” Elisabeth Björk, senior vice president, head of late cardiovascular, renal and metabolism, R&D BioPharmaceuticals, said in the release. “We look forward to bringing Forxiga to a patient population that has not had any approved oral medicines available before.”

The approval is based on data from the phase 3 DEPICT clinical program. The short-term (24-week) and long-term (52-week) data from DEPICT 1, along with the short-term data from DEPICT 2, demonstrated that 5 mg dapagliflozin daily, when given as an adjunct to adjustable insulin in patients with inadequately controlled type 1 diabetes, was associated with reductions from baseline in HbA1c (primary endpoint), weight and total daily insulin dose (secondary endpoints) at weeks 24 and 52, according to the release.

The safety profile of dapagliflozin in the type 1 diabetes studies was consistent with findings from the type 2 diabetes trials with the drug, apart from a higher number of observed cases of diabetic ketoacidosis (DKA) in patients who received dapagliflozin, according to the release.

Dapagliflozin is already indicated as a monotherapy and as part of combination therapy in adults with type 2 diabetes to improve glycemic control, with the additional benefits of weight loss and blood pressure reduction, as an adjunct to diet and exercise. In February, the FDA approved a label update for dapagliflozin, expanding its use for patients with type 2 diabetes and moderate renal impairment. As Endocrine Today previously reported, the expanded indication is intended for both dapagliflozin (Farxiga) and dapagliflozin plus metformin extended-release (Xigduo XL) and lowers the estimated glomerular filtration rate threshold to 45 mL/min/1.73m², indicating moderate chronic kidney disease, from 60 mL/min/1.73m².

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In a meta-analysis published in January 2018 in Diabetes Research and Clinical Practice and reported by Endocrine Today, researchers found that combined treatment with SGLT2 inhibitors and insulin is a viable option for treating patients with type 1 diabetes. In an analysis of four randomized controlled trials of therapy with SGLT2 inhibitors, including dapagliflozin, researchers found that SGLT2 inhibitors lowered HbA1c and were associated with lower daily doses of insulin and lower body weight compared with placebo. However, the researchers acknowledged that the study was limited by its small sample size, as three of the four trials included fewer than 100 participants. Furthermore, the studies included in the analysis used varying lengths of treatment, including two that ran for less than 12 weeks. – by Regina Schaffer

Disclosures: Björk is senior vice president and head of late cardiovascular, renal and metabolism at R&D BioPharmaceuticals.