High-dose dapagliflozin provides additional glycemic control in insulin-dependent type 2 diabetes

This study evaluated the safety and effectiveness of dapagliflozin in advanced type 2 diabetes over 2 years of treatment.

The sodium glucose cotransporter 2 (SGLT2) is a protein located in the kidneys which contributes to glucose uptake. Dapagliflozin (Farxiga) blocks the action of SGLT, and has been shown to reduce glucose absorption by the kidneys, increase urine excretion of glucose and increase glycemic control among type 2 diabetics. Following extensive research, dapagliflozin was approved by the United States Food and Drug Administration (FDA) on January 2014 for the treatment of type 2 diabetes. Since dapagliflozin acts independently of insulin, it is suggested to provide increased glycemic control in addition to insulin among patients with advanced diabetes.

This trial included more than 800 uncontrolled type 2 diabetics treated regularly with insulin. 197 patients were randomized to receive insulin plus a placebo, while the remaining patients received insulin plus different doses of dapagliflozin. 202 patients received insulin plus 2.5mg of dapagliflozin, 212 patients received insulin plus 5mg dapagliflozin, and 196 patients received insulin plus 10mg of dapagliflozin. 513 (63.6%) patients completed the 104 weeks of treatment and were included in the study analysis.

Among patients receiving dapagliflozin 10 mg, an average 0.78% decrease was noted in HbA1c (an indicator of average glucose levels over the past 3 months) levels by the end of the study, compared to a 0.43% average decrease among patients receiving a placebo. Over the two year study period, patients receiving a placebo had increased their daily insulin dose by an average of 18.3 IU in order to maintain adequate glycemic control, while dosing remained stable among patient groups receiving dapagliflozin. Specifically among patients receiving 10mg dapagliflozin average daily insulin dose was reduced by 0.8 IU by the end of the study.

Patients receiving a placebo gained an average weight of 1.83 kg during the study, while those receiving 10mg dapagliflozin lost an average weight of 1.5 kg. Therefore, by the end of the study, the difference in average weight between the placebo and dapagliflozin 10mg groups was 3.33 kg.

The proportion of patients reporting any adverse events was similar across all treatment groups. However, the proportion of patients reporting adverse events considered to be treatment-related was slightly higher in the dapagliflozin treatment groups (32.1%) versus the placebo group (22.8%). Urinary tract and genital infections were more common in all of the dapagliflozin treatment groups, reported by 13.8% of patients receiving 10 mg dapagliflozin, compared to only 3% among patients receiving a placebo.

This study concluded that dapagliflozin improves glycemic control, stabilizes insulin dosing and contributes to weight loss among insulin-dependent type 2 diabetics.

Bristol-Myers-Squibb, the manufacturers of dapagliflozin (Farxiga), sponsored this trial.

Consult with your physician regarding newly approved diabetes drugs such as dapagliflozin.