First oral hypoglycaemic licensed for add-on therapy in type I diabetes

The SGLT2 inhibitor dapagliflozin (Forxiga) can now be prescribed with insulin to treat overweight patients with type I diabetes inadequately controlled on insulin alone.

Dapagliflozin may be used as an adjunct to insulin when insulin alone does not provide adequate glycaemic control. | iStock.com/agrobacter
Dapagliflozin may be used as an adjunct to insulin when insulin alone does not provide adequate glycaemic control. | iStock.com/agrobacter

Forxiga (dapagliflozin) is licensed as an adjunct to insulin in patients with a BMI ≥27kg/m2, when insulin alone does not provide adequate glycaemic control. 

The recommended dose of dapagliflozin for use in type I diabetes is 5mg once daily in combination with insulin. In type II diabetes the recommended dose is 10mg once daily, either as monotherapy or as add-on combination therapy with other glucose-lowering agents, including insulin.

Monitor ketone levels

Before dapagliflozin treatment is initiated in type I diabetes risk factors for diabetic ketoacidosis (DKA) must be assessed and ketone levels measured. Treatment should not be started if ketones are elevated or if the patient is at increased risk of DKA.

As in type II diabetes, ketones should be monitored regularly during the first few weeks of treatment and monitoring frequency then individualised according to the patient's lifestyle and/or risk factors. Patients should be informed about the actions to take if levels are raised.

Patients at higher risk of DKA include:

  • patients with low insulin needs
  • patients not on optimal insulin dose or who have recent issues with non-compliance or recurrent errors with insulin dosing and who are unlikely to maintain adequate insulin dosing
  • patients who insist on maintaining caloric restriction, carbohydrate restriction or ketogenic diet or who chronically under-dose insulin
  • Patients unable or unwilling to monitor ketones
  • Patients with excessive alcohol consumption or who use illicit drugs
  • Patients using an insulin pump

Insulin therapy should be continuously optimised during treatment with dapagliflozin and any insulin dose reductions made cautiously to avoid DKA. If a marked reduction in insulin dose is needed discontinuation of dapagliflozin should be considered.

Clinical studies

The safety and efficacy of dapagliflozin as an adjunct to insulin in patients with type I diabetes with inadequate glycaemic control (HbA1c ≥7.5% and ≤10.5%) was assessed in two 24-week randomised controlled trials with a 28-week extension (DEPICT-1 and DEPICT-2; n=1646). 

Patients were randomised to one of three groups: dapagliflozin 5mg once daily; dapagliflozin 10mg once daily; or placebo. Patients' insulin dose was adjusted as appropriate throughout the study.

Significant improvements in HbA1c were observed in the dapagliflozin 5mg group compared with the placebo group at week 24 (mean changes from baseline relative to placebo of -0.42% and -0.37% in the two studies, respectively; p <0.0001 for both) and at week 52 (mean changes of -0.33% and -0.20%, respectively).

The study also showed that compared with placebo, dapagliflozin treatment was not associated with an increase in the percentage of patients with hypoglycaemic events. Patients receiving dapagliflozin 5mg also exhibited significantly greater weight loss over 52 weeks than those in the placebo group (adjusted mean changes in bodyweight from baseline relative to placebo of -2.56kg and -3.5kg in the two studies, respectively).

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