Empagliflozin as add-on to linagliptin in a fixed-dose combination in Japanese patients with type 2 diabetes: Glycaemic efficacy and safety profile in a 52-week, randomized, placebo-controlled trial

Aims: This double-blind, randomized, placebo-controlled trial (ClinicalTrials.gov NCT02453555) evaluated the efficacy and safety of empagliflozin (Empa) 10 or 25 mg as add-on to linagliptin (Lina) 5 mg (fixed-dose combination, Empa/Lina 10/5 or 25/5) in insufficiently controlled Japanese type 2 diabetes patients. Methods: The trial (40 sites; May 2015-March 2017) involved screening 433 adults (>= 20 years) who were treatment-naive or were using one oral antidiabetic drug for >= 12 weeks, which was discontinued at enrolment. Patients with HbA1c 7.5%-10.0% after >= 16 weeks of using Lina (pre-enrolment or during a 16-week, open-label period) and 2 weeks of using placebo (Plc) for Empa/Lina 10/5, plus Lina, were randomized (2:1) to once-daily Empa/Lina 10/5 (n = 182) or Plc/Lina 10/5 (n = 93) for 24 weeks. Patients with HbA1c >= 7.0% at Week 24 received Empa/Lina up-titrated to 25/5 (n = 126) or the corresponding placebo (n = 80), per randomization, from Week 28; 172 Empa/Lina and 84 Plc/Lina patients completed 52 weeks. Results: Change from baseline in HbA1c was greater (P < .0001) with Empa/Lina than with Plc/Lina at Week 24 (primary outcome, -0.93% vs 0.21%; adjusted mean difference, -1.14%) and Week 52 (-1.16% vs 0.06%; adjusted mean difference, -1.22%). More patients with HbA1c < 7.0% and greater decreases in fasting plasma glucose, body weight and systolic blood pressure were seen in the Empa/Lina group than in the Plc/Lina group. Empa/Lina was well tolerated. The adverse events that were more frequent with Empa/Lina were known empagliflozin-associated events (eg, increased urination, increased blood ketones). There were no adjudication-confirmed diabetic ketoacidosis events or lower limb amputations. Conclusions: These results support the notion that empagliflozin-linagliptin in fixed-dose combination is a therapeutic option for Japanese patients with type 2 diabetes.