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Diabetes Hypoglycaemia Incidence of Hypoglycaemia in Patients with Type 2 Diabetes – A Subgroup Analysis from the GINGER study Andreas Fritsche, 1 Almut Hahn, 2 Wolfgang Landgraf 3,4 and Hans-Ulrich Häring 1 , for the GINGER Study Group 1. Fourth Medical Department and Policlinic, University Tübingen; 2. CROMSOURCE GmbH, Aachen; 3. Sanofi-Aventis, Frankfurt; 4. Third Medical Department and Policlinic, University Dresden Abstract 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 Keywords Basal-bolus, hypoglycaemia, insulin glargine, insulin glulisine, premixed insulin Disclosure: The authors have no conflicts of interest to declare. Acknowledgments: This study was funded by Sanofi. Hans-Ulrich Häring has received research grants from Sanofi and Novo Nordisk and has served as a consultant for Novo Nordisk, Sanofi and Merck Sharpe & Dohme. He has also received honoraria from all of the above companies for consultancy and lecture fees. Andreas Fritsche has received research grants from Sanofi and Novo Nordisk and has served as a consultant for Novo Nordisk and Sanofi. He has also received honoraria from all of the above companies for consultancy and lecture fees. Wolfgang Landgraf is an employee of Sanofi. Almut Hahn is a consultant for Sanofi. Editorial support was provided by Leigh Prevost, BSc, and Tom Claus, PhD, of PPSI (a PAREXEL company), and was funded by Sanofi. Received: 20 December 2012 Accepted: 14 March 2013 Citation: European Endocrinology 2013;9(1):i–iii. Correspondence: Andreas Fritsche, Medizinische Klinik IV, Universität Tübingen, Otfried Müller Straße 10, D-72076 Tübingen, Germany. E: andreas.fritsche@med.uni-tuebingen.de Support: The publication of this article was funded by Sanofi. The views and opinions expressed are those of the authors and not necessarily those of Sanofi. Hypoglycaemia is a clinically important and potentially dangerous side effect of insulin therapy in patients with Type 2 diabetes mellitus (T2DM). 1,2 The basal-bolus insulin strategy has been studied in the Glulisine in Combination with Insulin Glargine in an Intensified Insulin Regimen (GINGER) study in a population with long-standing insulin- treated T2DM, with or without metformin, who were not controlled adequately with their previous premixed insulins. 3 The study demonstrated that an intensified basal-bolus regimen using insulin glargine plus insulin glulisine provided significantly better glycaemic control and numerically lower overall hypoglycaemia than premixed insulin therapy. The premixed insulin group in the GINGER study comprised two subgroups: those taking neutral protamine Hagedorn (NPH) insulin plus regular insulin and those taking biphasic insulin aspart 70/30. The aim of this post-hoc analysis was to determine the overall hypoglycaemic event rates in the insulin glargine plus insulin glulisine group with that of the premixed insulin subgroups, and to compare i hypoglycaemia risk relative to the glycaemic control achieved at the end of the GINGER study. Methods Details of the study design and patient population have been published previously. 3 In brief, this was a 52-week, open-label, active-controlled, randomised, multi-national clinical trial that compared basal insulin glargine plus mealtime insulin glulisine with an optimised conventional therapy of twice-daily premixed insulin therapy. Male and female patients aged 18 to 75 years were eligible for inclusion in the study if they had had T2DM for ≥5 years and had been treated with a stable regimen of twice-daily injections of premixed insulin (NPH plus regular insulin, or NPH plus either lispro or aspart in a ratio of 70/30), with or without metformin for ≥3 months before screening, and had HbA1c between 7.5  % and 11.0  % at screening and randomisation. Oral antidiabetic drugs, except metformin, were not allowed. Exclusion criteria included body mass index >38  kg/m² and ≥2 severe hypoglycaemic episodes within the past 3 months. © Touch ME dical ME dia 2013