Comparison between a basal-bolus and a premixed insulin regimen in individuals with type 2 diabetes-results of the GINGER study

Aim: To compare the efficacy and safety of an intensified insulin regimen, using insulin glargine (glargine) once daily and pre-meal insulin glulisine (glulisine) (basal-bolus), with a conventional therapy, using premixed insulin (premix) twice daily. Methods: This 52-week, open-label, randomized, multinational, multicentre trial included 310 subjects with type 2 diabetes (T2D) on premix, with or without metformin, who were randomized to a basal-bolus regimen with glargine and glulisine (n = 153; mean +/- s.d. age 60.2 +/- 7.5 years; HbA1c 8.6 +/- 0.8%; weight 87.0 +/- 15.1 kg; T2D duration 12.8 +/- 5.8 years) or twice-daily premix (n = 157; age 60.9 +/- 7.8 years; HbA1c 8.5 +/- 0.9%; weight 84.3 +/- 15.0 kg; T2D duration 12.5 +/- 6.8 years). The primary endpoint was change in HbA1c from baseline to endpoint. Results: Mean decrease in baseline-to-endpoint HbA1c for basal-bolus vs. premix was -1.31 vs. -0.80% (difference: -0.476%; 95% Cl: -0.714, -0.238; p = 0.0001, ancova). More subjects reached HbA1c < 7.0% in the basal-bolus group than in the premix group [68 (46.6%) vs. 43 (27.9%); p = 0.0004], while they also experienced significantly lower mean +/- s.d. daytime (-2.7 +/- 2.3 vs. -2.3 +/- 2.5 mmol/l; p = 0.0033) and postprandial (-3.1 +/- 2.6 vs. -2.5 +/- 2.8 mmol/l; p < 0.0001) blood glucose. Endpoint daily insulin doses were 98.0 +/- 48.7 vs. 91.3 +/- 44.3 IU (p = 0.2104); mean weight gain was +3.6 +/- 4.0 vs. +2.2 +/- 4.5 kg (p = 0.0073). Mean number of overall hypoglycaemic events with basal-bolus and premix was 13.99 and 18.54 events/patient year, respectively (difference: -3.90; 95% CI: -10.40, 2.60; p = 0.2385). Conclusions: An intensified basal-bolus regimen using glargine/glulisine results in a significantly superior glycaemic control vs. premix therapy in a population with long-standing insulin-treated T2D, with no increase in the rates of hypoglycaemia.