Initial combination of empagliflozin and linagliptin in subjects with type 2 diabetes

OBJECTIVE To evaluate the efficacy and safety of empagliflozin/linagliptin in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS Subjects not receiving antidiabetes therapy for ≥12 weeks were randomized to empagliflozin 25 mg/linagliptin 5 mg (n = 137), empagliflozin 10 mg/linagliptin 5 mg (n = 136), empagliflozin 25 mg (n = 135), empagliflozin 10 mg (n = 134), or linagliptin 5 mg (n = 135) for 52 weeks. The primary end point was change from baseline in HbA_1c at week 24. RESULTS Mean HbA_1c at baseline was 7.99-8.05% (64 mmol/mol). At week 24, adjusted mean (SE) changes from baseline in HbA_1c with empagliflozin 25 mg/linagliptin 5 mg, empagliflozin 10 mg/linagliptin 5 mg, empagliflozin 25 mg, empagliflozin 10 mg, and linagliptin 5 mg were 21.08 (0.06)% (211.8 [0.7] mmol/mol), 21.24 (0.06)% (213.6 [0.7] mmol/mol), 20.95 (0.06)% (210.4 [0.7] mmol/mol), 20.83 (0.06)% (29.1 [0.7] mmol/mol), and 20.67 (0.06)% (27.3 [0.7] mmol/mol), respectively. Reductions in HbA_1c were significantly greater for empagliflozin 25 mg/linagliptin 5 mg compared with linagliptin 5 mg (P < 0.001) but not compared with empagliflozin 25 mg and were significantly greater for empagliflozin 10 mg/linagliptin 5 mg compared with the individual components (P < 0.001 for both). At week 24, 55.4%, 62.3%, 41.5%, 38.8%, and 32.3% of subjects with baseline HbA_1c ≥7% (≥53 mmol/mol) reached HbA_1c <7% with empagliflozin 25 mg/linagliptin 5 mg, empagliflozin 10 mg/linagliptin 5 mg, empagliflozin 25 mg, empagliflozin 10 mg, and linagliptin 5 mg, respectively. Efficacy was maintained at week 52. The proportion of subjects with adverse events (AEs) over 52 weeks was similar across groups (68.9-81.5%), with no confirmed hypoglycemic AEs. CONCLUSIONS Reductions from baseline in HbA_1c with empagliflozin/linagliptin were significantly different versus linagliptin and empagliflozin 10 mg but not versus empagliflozin 25 mg. Empagliflozin/linagliptin was well tolerated.