Data presented from a phase 2b study with empagliflozin, a sodium glucose cotransporter-2, which increases renal glucose excretion, showed reductions in hemoglobin (Hb) A1c, fasting plasma glucose (FPG), and body weight in patients with type 2 diabetes at 90 weeks. Hans-Juergen Woerle, MD, Vice President, Boehringer Ingelheim, Germany, presented this randomized, multinational, open-label extension study in a late-breaking abstract session at the 2012 ADA annual meeting.
A total of 659 adults with type 2 diabetes who had participated in 1 of two 12-week, blinded, dose-finding trials of empagliflozin were treated for an additional 78 weeks with open-label empagliflozin (10 mg or 25 mg) alone or added to metformin, with metformin alone, or with metformin plus sitagliptin.
Empagliflozin showed sustained efficacy over 90 weeks, with a clearly significant and meaningful efficacy with both doses, said Dr Woerle.
Average HbA1c was approximately 8% at baseline. At 90 weeks, HbA1c levels were reduced with the 10-mg and 25-mg doses of empagliflozin monotherapy (–0.34% and –0.47%, respectively), metformin monotherapy (–0.56%), both doses of empagliflozin in combination with metformin (–0.34% and –0.63%, respectively), and sitagliptin plus metformin (–0.40%).
FPG was reduced with empagliflozin 10 mg (–30.4 mg/dL) and 25 mg (–27.8 mg/dL) compared with metformin (–26 mg/dL). FPG reductions were greater with both doses of empagliflozin in combination with metformin compared with sitagliptin plus metformin.
Body weight ranged from 82 kg to 87 kg at baseline. Weight loss was greater in all empagliflozin groups compared with the metformin alone or the sitagliptin plus metformin groups; reductions were –2.24 kg with the 10-mg dose and –2.61 kg with the 25-mg dose of empagliflozin alone compared with –1.28 kg with metformin. Reductions with sitagliptin plus metformin were small compared with the 2 empagliflozin doses in combination with metformin.
Empagliflozin was generally well tolerated. Adverse events (AEs) were mostly mild or moderate and reported in 63.2% to 74.1% of patients taking empagliflozin, and in 69.6% of patients taking metformin or sitagliptin plus metformin.
Hypoglycemic events were more frequent with metformin or with sitagliptin plus metformin than with empagliflozin.
Patients with Liver Impairment
In a phase 1, open-label, parallel-group study presented by Sreeraj Macha, PhD, Boehringer Ingelheim, Ridgefield, CT, the drug was found to be safe and well tolerated in patients with varying degrees of liver impairment.
The increased exposure to empagliflozin in patients with hepatic impairment was less than 2-fold. Therefore, the investigators concluded that dose adjustment of empagliflozin is not required in this patient population.
The 36 patients in this study—8 each with mild, moderate, or severe hepatic impairment and 12 controls—were given a single dose of empagliflozin 50 mg and were monitored for 5 days in the study center. AEs were reported in 5 subjects with hepatic impairment and in 6 healthy persons.
A phase 3 clinical trial with empagliflozin is currently in development, with planned enrollment of more than 14,500 patients.