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. Issue 9 (1st June 2018)

• Record Type: Journal Article
• Authors: Kawamori, Ryuzo; Haneda, Masakazu; Suzaki, Keiko; Cheng, Gang; Shiki, Kosuke; Miyamoto, Yuki; Solimando, Fernando; Lee, Christopher; Lee, Jisoo; George, Jyothis
• Is Part Of: Diabetes, obesity & metabolism. Volume 20:Issue 9(2018)
• Page Start: 2200
• Page End: 2209
• Publication Date: 2018-06-01
• Subjects: empagliflozin -- glycaemic control -- linagliptin -- phase III study -- randomized trial -- type 2 diabetes; Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.13352
• Languages: English
• ISSNs: 1462-8902

Abstract

Abstract : 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.