Non-Inferiority of Insulin Glargine Versus Insulin Detemir on Blood Glucose Variability in Type 1 Diabetes Patients: A Multicenter, Randomized, Crossover Study

Background: This study compared the effects of insulin glargine and insulin detemir on blood glucose variability under clinical practice conditions in patients with type 1 diabetes (T1D) using glulisine as the mealtime insulin. Methods: This was a multicenter, crossover trial in 88 randomized T1D patients: 54 men and 34 women, 46.8 +/- 13.7 years old, with a duration of diabetes of 18 9 years and hemoglobin A1c level of 7.1 +/- 0.7%. The per-protocol population included 78 patients: 44 received glargine/detemir and 34 detemir/glargine in the first/second 16-week period, respectively. The primary end point was the coefficient of variation (CV) of fasting blood glucose (FBG). Secondary end points included variability of pre-dinner blood glucose, mean amplitude of glycemic excursions, mean of daily differences, and doses and number of daily insulin injections. The non-inferiority criterion was an insulin glargine/insulin detemir FBG CV ratio with a 95% confidence interval (CI) upper limit <= 1.25. Results: The non-inferiority criterion was satisfied with a mean value of 1.016 (95% CI=0.970-1.065). Intention-to-treat analysis confirmed the non-inferiority with a 95% CI upper limit=1.062. No significant differences were found on secondary objectives, but there was a trend to higher doses and number of daily injections with insulin detemir. A total of eight (four glargine and four detemir) patients reported nine serious adverse events (including one severe episode of hypoglycemia). None of them was considered as related to basal insulins. Serious adverse events led to treatment discontinuation in two patients of the detemir group and none in the glargine group. Conclusions: In T1D patients under clinical practice conditions, insulin glargine was non-inferior to insulin detemir regarding blood glucose variability, as assessed by CV of FBG.