Linagliptin as add‐on to empagliflozin in a fixed‐dose combination in Japanese patients with type 2 diabetes: Glycaemic efficacy and safety profile in a two‐part, randomized, placebo‐controlled trial. Issue 1 (6th September 2018)

• Record Type: Journal Article
• Authors: Kaku, Kohei; Haneda, Masakazu; Tanaka, Yuko; Lee, Ganghyuck; Shiki, Kosuke; Miyamoto, Yuki; Solimando, Fernando; Lee, Jisoo; Lee, Christopher; George, Jyothis
• Is Part Of: Diabetes, obesity & metabolism. Volume 21:Issue 1(2019)
• Page Start: 136
• Page End: 145
• Publication Date: 2018-09-06
• 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.13496
• Languages: English
• ISSNs: 1462-8902

Abstract

Abstract : Aims: This two‐part, double‐blind, double‐dummy, randomized, placebo‐controlled trial (83 sites) evaluated the efficacy and safety of empagliflozin (Empa) 10 or 25 mg and linagliptin (Lina) 5 mg fixed‐dose combinations (FDCs) in Japanese patients with type 2 diabetes mellitus (T2DM) who were poorly controlled with Empa. Materials and methods: Patients (previously drug‐naive or using one oral antidiabetic drug for ≥ 12 weeks) entered an open‐label stabilization period (16 weeks, Empa 10 mg [Part A] or Empa 25 mg [Part B]). Subsequently, they received Empa 10 mg plus placebo (Plc) for Empa/Lina10/5 (Empa/Plc 10/5; Part A) or Empa 25 mg plus Plc for Empa/Lina 25/5 (Empa/Plc 25/5; Part B) for 2 weeks. Patients with HbA1c 7.5–10.0% were randomized (1:1) to a 24‐week regimen of once‐daily Empa/Lina 10/5 ( n = 107) or Empa/Plc 10/5 ( n = 108) in Part A, or to Empa/Lina 25/5 ( n = 116) or Empa/Plc 25/5 ( n = 116) in Part B, with a 28‐week extension period in Part B. Results: Change from baseline in HbA1c at Week 24 was greater ( P < 0.0001) with Empa/Lina than with Empa/Plc (primary outcome, Empa/Lina 10/5: −0.94 vs −0.12%; adjusted mean difference, −0.82%; Empa/Lina 25/5: −0.91 vs −0.33%; adjusted mean difference, −0.59%). Over 24‐ and 52‐week periods, higher proportions of patients achieved HbA1c < 7.0% and greater decreases in fasting plasma glucose were observed with Empa/Lina compared with Empa/Plc. Empa/Lina was well tolerated, with no unexpected adverse events or diabetic ketoacidosis. One case of confirmed hypoglycaemia with Empa/Plc 25/5 was reported. Conclusions: These results support Empa/Lina FDC as a potential option for Japanese patients with T2DM who require combination therapy.ClinicalTrials.gov NCT02489968.