The results of a 24-week phase III clinical trial, which showed that treatment with the investigational compound Empagliflozin as monotherapy produced statistically significant reductions in HbA1c versus placebo, in adults with type 2 diabetes ( T2D ) who had never received treatment or had not received treatment in the last 12 weeks, were presented at the American Diabetes Association ( ADA ) 73rd Scientific Sessions.
Empagliflozin is a member of the sodium glucose co-transporter-2 ( SGLT2 ) inhibitor class of compounds, and is being investigated for the reduction of blood glucose levels in adults with T2D. The emerging SGLT2 inhibitor class removes excess glucose through the urine by blocking glucose re-absorption by the kidney.
The study in people with T2D ( n=899 ) investigated the safety and efficacy of two doses ( 10 mg and 25 mg ) of Empagliflozin for 24 weeks. Results of the primary endpoint showed placebo-adjusted reductions in HbA1c from baseline to week 24 of 0.74% and 0.85% ( p less than 0.001 ) for the 10 mg and 25 mg doses, respectively.
Sitagliptin ( Januvia ) 100 mg ( which was used as an active comparator to validate the trial design and not for a head-to-head comparison with Empagliflozin ) showed a reduction in HbA1c of 0.73% compared to placebo ( p less than 0.001 ).
Study findings at 24 weeks also showed significant improvements with Empagliflozin in secondary endpoints:
Findings included statistically significant placebo-adjusted reductions in systolic blood pressure of 2.6 mmHg for Empagliflozin 10 mg ( p=0.023 ) and 3.4 mmHg for Empagliflozin 25 mg ( p=0.003 ). Sitagliptin 100 mg did not show a statistically significant change in systolic blood pressure versus placebo.
After 24 weeks, body weight significantly decreased by 4.25 lbs and 4.74 lbs ( p less than 0.001 ) in patients treated with Empagliflozin 10 mg and 25 mg, respectively, versus placebo. Sitagliptin 100 mg showed a weight increase of 1.15 lbs versus placebo ( p=0.036 ).
Changes in diastolic blood pressure were statistically significant for the Empagliflozin 25 mg treatment group only ( 1.9 mmHg reduction versus 0.5 mmHg reduction for placebo, p=0.030 ).
The proportions of patients reporting drug-related adverse events from each study group were: 12.1%, Empagliflozin 10 mg; 17.5%, Empagliflozin 25 mg; 7.4%, placebo; and 8.5%, Sitagliptin.
Adverse events consistent with urinary tract infection were reported in 6.7% and 5.4% of randomized patients on Empagliflozin 10 mg and 25 mg, respectively, and in 5.2% on placebo and 4.9% on Sitagliptin.
Adverse events consistent with genital infection were reported in 3.1% and 4.0% of patients on Empagliflozin 10 mg and 25 mg, respectively, and in 0.0% on placebo and 0.9% on Sitagliptin.
One patient in each study group experienced a confirmed hypoglycemic event, none of which required assistance.
Additionally, a subset of patients with baseline HbA1c greater than 10% ( mean=11.5%, N=87 ), which was above the study inclusion criteria, were placed on open-label Empagliflozin 25 mg for 24 weeks and obtained a mean reduction of 3.7% from baseline HbA1c.1 Drug-related adverse events were reported by 12.6% of patients included in this subset.
The 24-week, randomized, double-blind, placebo-controlled trial investigated the safety and efficacy of Empagliflozin in drug-naive patients with type 2 diabetes. Patients were randomized to receive Empagliflozin 10 mg ( n=224 ) or 25 mg per day ( n=224 ), Sitagliptin 100 mg per day ( n=223 ) or placebo ( n=228 ) for 24 weeks. Patients with HbA1c more than 10% ( n=87 ) received open-label Empagliflozin 25 mg per day for 24 weeks. The primary endpoint of the trial was change from baseline HbA1c at week 24. Secondary endpoints were change from baseline in body weight, systolic blood pressure and diastolic blood pressure at week 24. ( Xagena )
Source: Lilly, 2013