Insulin glargine compared with premixed insulin for management of insulin-naive type 2 diabetes patients uncontrolled on oral antidiabetic drugs: the open-label, randomized GALAPAGOS study

Aims: Demonstrate superiority of insulin glargine (+/- glulisine) strategy versus premixed insulin strategy for percentage of patients reaching HbA1c <7% (<53 mmol/mol) at study end without any documented symptomatic hypoglycemia (bloof glucose [BG] <= 3.1 mmol/L) in type 2 diabetes (T2DM) patients failing oral agents. Methods: This 24-week, open-label, multinational trial randomized patients to glargine OD or premix OD or BID, continuing metformin +/- insulin secretagogue (IS). Second premix injection could be added any time; glulisine could be added with main meal in glargine OD patients with HbA1c >= 7% and fasting blood glucose (FBG) <7 mmol/L at week 12. IS was stopped with any second injection. Insulin titration targeted FBG <= 5.6 mmol/L. Results: Modified intent-to-treat population comprised 923 patients (glargine, 462; premix, 461). Baseline characteristics were similar (mean 12DM duration: 9 years; HbA1c: 8.7% (72 mmol/mol); FBG: 10.4 mmol/L). Primary endpoint was achieved by 332% of glargine (+/- glulisine) and 31.4% of premix patients. Superiority was not demonstrated, but non-inferiority was (pre-specified margin: 25% of premix rate). More patients using premix achieved target (52.6% vs. 43.2%, p = 0.005); symptomatic hypoglycemia was less with glargine (1.17 vs. 2.93 events/patient-year). Conclusions: Glargine (+/- glulisine) and premix strategies resulted in similar percentages of well-controlled patients without hypoglycemia, with more patients achieving target HbA1c with premix whereas overall symptomatic hypoglycemia was less with glargine. (C) 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license