Newly-Approved Empagliflozin for Obese Patients with Type 2 Diabetes

San Francisco—After 52 weeks of treatment, obese patients with type 2 diabetes who received empagliflozin as an add-on therapy to daily insulin injections had improved glucose control, experienced weight loss, and had no increase in hypoglycemia risk compared with a placebo group, according to a randomized, double-blind, placebo-controlled trial.

Julio Rosenstock, MD, the study’s lead author, presented the results during a symposium at the ADA meeting. The findings were simultaneously published in Diabetes Care [2014;37(7):1815-1823].
In March, the FDA rejected the approval of empagliflozin because of deficiencies at a Boehringer Ingelheim facility that produced the drug. Eli Lilly and Company and Boehringer Ingelheim, the drug’s manufacturer, said in a news release that they planned on working with the FDA to bring empagliflozin to the market. It was later approved for use in Europe. In addition, in August empagliflozin was approved by the FDA for use in the United States.  

Empagliflozin, a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, had been found in previous trials to improve glycemic control and not increase the risk for hypoglycemia when combined with basal insulin, according to Dr. Rosenstock. The FDA has also approved 2 other SGLT-2 inhibitors: canagliflozin in March 2013 and dapagliflozin in January.

This study was conducted from March 2011 to April 2013 at 104 centers in 14 countries. The researchers evaluated 566 patients who required multiple, daily, high doses of basal/bolus insulin injections with or without metformin.

Patients were required to have normal renal function, a hemoglobin A1c (HbA1c) level between 7.5% and 10%, and a body mass index (BMI) from 30 kg/m² to 45 kg/m². Patients were randomized to receive placebo, 10 mg of empagliflozin, or 25 mg of empagliflozin.

At baseline, the groups were well-balanced. The mean age was 56.7 years, 45% of patients were male, 94% were white, 69% had type 2 diabetes for >10 years, and 71% received insulin plus metformin. The mean HbA1c level at baseline was 8.3%, and the mean BMI was 34.8 kg/m².

In each group, >80% of patients completed 52 weeks of treatment. Dr. Rosenstock said there were no imbalances between the groups regarding the reasons for study withdrawal or discontinued therapy.
During the first 18 weeks, the insulin dose remained stable, so the authors could assess the drug’s affect, according to Dr. Rosenstock. From weeks 19 to 40, insulin adjustments were made to conform with clinical practice. From weeks 41 to 52, there were no further insulin changes.

At week 52, the fasting plasma glucose (FPG) decreased 19.3 mg/dL in the 10 mg empagliflozin group and 23.4 mg/dL in the 25 mg empagliflozin group compared with the placebo group (P<.0001 for both). At that same time, the HbA1c decreased 0.38% and 0.46%, respectively, compared with patients who took placebo (P<.001 for both).

At week 18, the FPG was reduced by 21 mg/dL in the 10 mg empagliflozin group and 27.9 mg/dL in the 25 mg empagliflozin group compared with the placebo group (P<.0001 in both comparisons). At that same time, the HbA1c decreased 0.44% and 0.52%, respectively, compared with patients who took placebo (P<.001 for both).

Compared with the placebo group, patients who received 10 mg of empagliflozin had a 2.4 kg reduction in body weight and patients who received 25 mg of the drug lost 2.5 kg (P<.001 for both). In each group, total cholesterol and triglycerides increased, although the differences were not significant.

More than 80% of patients in each group had an adverse event, while approximately 5% in each group had an adverse event that led to study discontinuation. However, there were no significant differences between the groups.

Dr. Rosenstock said empagliflozin was well-tolerated except for an increase in genital infections, which is common with SGLT-2 inhibitors.—Tim Casey