SGLT-2 inhibitors approved for the first time to treat type 1 diabetes

On March 25, AstraZeneca announced that the European Medicines Agency (EMA) officially approved its SGLT-2 inhibitor Forxiga (dapagliflozin) as an adjunct therapy to insulin for patients with type 1 diabetes (BMI ≥ 27) who do not control blood sugar well with the optimal dose of insulin alone.

This is the first time that the EMA has approved an oral drug as an adjunct therapy to insulin for patients with type 1 diabetes. It is AstraZeneca's first drug approved for the treatment of type 1 diabetes and the first time that an SGLT-2 inhibitor has been approved for patients with type 1 diabetes.

The EMA's approval is mainly based on the results of the Phase III DEPICT clinical project conducted in patients with type 1 diabetes. The 24-week short-term results and 52-week long-term results of the DEPICT-1 study and the 24-week short-term results of the DEPICT-2 study all show that once-daily oral administration of 5 mg of Forxiga as an adjunct therapy for patients with type 1 diabetes who do not control blood sugar well with insulin alone can achieve clinically significant improvements in patients' HbA1c levels (primary endpoint), weight (secondary endpoint), and daily insulin dose (secondary endpoint) compared to baseline values.

In terms of safety, except for the slightly higher incidence of ketoacidosis, the adverse reaction data of Forxiga in patients with type 1 diabetes are consistent with the previous data in patients with type 2 diabetes. Ketoacidosis is a common complication in patients with type 1 diabetes, more common than in patients with type 2 diabetes.

SGLT-2 is called sodium-glucose cotransporter-2 in Chinese. It is mainly expressed in the kidneys and its main function is to help the kidneys reabsorb glucose. SGLT-2 inhibitors are new diabetes drugs that have been launched in recent years. They mainly play a hypoglycemic effect by reducing the renal reabsorption of glucose and promoting the excretion of excess glucose through urine. They are regarded as a new way to treat diabetes that is different from traditional hypoglycemic drugs and are also a hot target for the development of diabetes drugs in recent years.

So far, a total of 7 SGLT-2 inhibitors have been approved for marketing worldwide, of which togliflozin, rugliflozin and ipragliflozin have only been approved in Japan. Statistics of the three most popular SGLT-2 inhibitors (the sales of Merck's ipragliflozin are not disclosed) show that the market size of SGLT-2 inhibitor drugs has exceeded US$2.9 billion.

From the growth trend of specific varieties, canagliflozin finally lost the top spot in the SGLT-2 field in 2018 due to the most safety warnings, and its share has shrunk year by year. Forxiga has been approved in the EU and the US as an adjunct therapy to diet and exercise to improve blood sugar control in patients with type 2 diabetes, and has been proven in clinical studies to have additional benefits of weight loss, lowering blood pressure, and reducing the risk of cardiovascular events, with good sales growth momentum.

Forxiga's application for approval as an insulin-adjunct therapy for patients with type 1 diabetes has also been submitted in Japan and the United States, and results are expected to be obtained in the first half of 2019 and 2019, respectively. On March 22, the FDA rejected the application for approval of sotagliflozin, a dual SGLT-1/2 inhibitor jointly developed by Sanofi and Lexicon, for the treatment of type 1 diabetes. The specific reason was not disclosed, but sotagliflozin's application for approval in the EU for this indication has been positively recommended by CHMP, and the official approval result will not be made until the second half of this year.

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