How effective and safe is dapagliflozin as an add-on therapy to insulin in patients with type 1 diabetes?

This study evaluated the most effective and safe dose of dapagliflozin (Farxiga) as an additional treatment to insulin in patients with type 1 diabetes (T1D). The authors concluded that 10 mg of dapagliflozin as an add-on to insulin treatment resulted in improved blood glucose (sugar) control, reduced insulin dosage, and body weight without causing an elevated risk of low blood glucose in these patients.

T1D is a chronic disease in which the pancreas produces little or no insulin. Patients with T1D require life-long insulin therapy to regulate their blood glucose. Life-long insulin therapy can cause low blood glucose, weight gain, fatty acid imbalances, and impaired responses to insulin.

Dapagliflozin belongs to a class of medicines known as sodium-glucose cotransporter-2 inhibitors (SGLT-2is). SGLT-2is are used to reduce blood glucose levels along with diet and exercise in adult patients with T2D. SGLT-2is work by decreasing the re-uptake of glucose in the kidneys. Evidence shows that SGLT-2is addition to insulin therapy leads to benefits when compared to insulin treatment alone. However, there is no consensus regarding the addition of an effective and safe dose of dapagliflozin to insulin therapy in patients with T1D.

This analysis included 13 studies that included a total of 10,701 patients with T1D. Patients received 5 mg of dapagliflozin and insulin or 10 mg of dapagliflozin and insulin. The control group was given insulin alone. Changes in glycated hemoglobin (HbA1c; a measure of blood glucose control over the past 3 months) levels, total insulin daily dose (TIDD), 24-hour continuous glucose monitoring (24 h CGM) values, and side effects were determined. The average study duration was 41.54 weeks.

10 mg of dapagliflozin therapy significantly lowered the HbA1c level compared to 5 mg of dapagliflozin. 5 mg of dapagliflozin therapy significantly decreased the HbA1c level compared to insulin alone.

Reduced TIDD and significant improvements in 24 h CGM occurred with both 5 mg and 10 mg of dapagliflozin compared to insulin alone. Body weight significantly decreased from baseline values with 5 mg and 10 mg of dapagliflozin compared to insulin alone.

Both doses of dapagliflozin increased the occurrence of diabetic ketoacidosis (DKA; a serious complication of T1D that involves the buildup of acids in the blood), urinary tract infections, and genital infections compared to insulin alone. However, the risk of hypoglycemia (dangerously low blood glucose levels) was not significantly increased with dapagliflozin treatment. 

The study showed that 10 mg of dapagliflozin as an add-on to insulin treatment may be more beneficial than 5 mg of dapagliflozin in reducing HbA1c levels and body weight in patients with T1D.

This analysis included studies with different follow-up periods, some of which were short in duration. Further studies are needed.