Incidence of Hypoglycaemia in Patients with Type 2 Diabetes - A Subgroup Analysis from the GINGER study

Introduction: The Glulisine in Combination with Insulin Glargine in an Intensified Insulin Regimen (GINGER) study compared insulin glargine plus insulin glulisine with premixed insulin in the treatment of patients with Type 2 diabetes mellitus (T2DM). This was a post-hoc analysis of hypoglycaemia rates in subgroups from the GINGER study. Methods: This analysis compared the once-daily glargine plus mealtime glulisine group (n=153, four injections/day) with the overall twice-daily premixed insulin group (n=157, two injections/day), which consisted of two subgroups receiving either neutral protamine Hagedorn (NPH) plus regular insulin (n=93) or biphasic insulin aspart 70/30 (n=63). Observed and predicted hypoglycaemia rates relative to endpoint HbA_1c for both the total population and those patients who experienced ≥1 episodes of any hypoglycaemia were estimated. Results: The overall hypoglycaemic event rate (episodes per patient-year) for patients receiving glargine plus glulisine was numerically but not significantly lower (-24.5 %) compared with the overall premixed insulin group (14.0±24.2 versus 18.5±36.9; p=0.12) and significantly lower (-43.3 %) compared with the biphasic insulin aspart 70/30 subgroup (24.7±48.5; p=0.02). In patients with ≥1 episode of hypoglycaemia during treatment, the overall hypoglycaemic event rate was significantly lower (-26.5 %) in patients receiving glargine plus glulisine versus overall premixed insulin (18.5±26.3 versus 25.1±41.1; p=0.044) and significantly lower (-40.7 %) than in patients receiving biphasic insulin aspart 70/30 (31.1±52.7; p=0.009). Glargine/glulisine treatment maintained a more consistent and numerically lower hypoglycaemia rate at all achieved HbA_1c endpoints compared with premixed insulin treatment. Conclusion: This post-hoc analysis of the GINGER study showed that the frequency of hypoglycaemia in T2DM patients was lowered to a greater extent by insulin glargine plus insulin glulisine in a comparison with premixed biphasic insulin aspart 70/30 than was previously shown in a comparison with overall premixed insulin. Trial Identifier: NCT00174668.