New Insulin Glargine 300 Units/mL Versus Glargine 100 Units/mL in People With Type 2 Diabetes Using Basal and Mealtime Insulin: Glucose Control and Hypoglycemia in a 6-Month Randomized Controlled Trial (EDITION 1) Featured Article: Matthew C. Riddle, Geremia B. Bolli, Monika Ziemen, Isabel Muehlen-Bartmer, Florence Bizet, and Philip D. Home, on behalf of the EDITION 1 Study Investigators Diabetes Care Volume 37: 2755-2762 October, 2014

STUDY OBJECTIVE   To compare the efficacy and safety of new insulin glargine 300 units/mL (Gla-300) with glargine 100 units/mL (Gla-100) in people with type 2 diabetes on basal insulin plus mealtime insulin Riddle M. C. et al. Diabetes Care 2014;37:2755-2762

STUDY DESIGN AND METHODS EDITION 1 was a 6-month, multinational, open-label, parallel-group study Adults with HbA1c of 7.0–10.0% were randomized to Gla-300 or Gla-100 once daily, with dose titration seeking fasting plasma glucose of 4.4–5.6 mmol/L Primary end point was HbA1c change from baseline Main secondary end point was percentage of participants with one or more confirmed or severe nocturnal hypoglycemia from week 9 to month 6 Riddle M. C. et al. Diabetes Care 2014;37:2755-2762

RESULTS Participants had mean age 60 years, diabetes duration 16 years, BMI 36.6 kg/m2, and HbA1c 8.15% HbA1c reduction was equivalent between regimens Fewer participants reported one or more confirmed or severe nocturnal hypoglycemic events between week 9 and month 6 with Gla-300 Nocturnal hypoglycemia incidence and event rates were also lower with Gla-300 in the first 8 weeks of treatment No between-treatment differences in tolerability or safety were identified Riddle M. C. et al. Diabetes Care 2014;37:2755-2762

Data are presented as mean (SD), unless otherwise indicated. Riddle M. C. et al. Diabetes Care 2014;37:2755-2762

Figure 1—Clinical measures during treatment in the mITT population by visit and with last observation carried forward (LOCF). A: HbA1c. B: FPG. C: Daily basal insulin and mealtime insulin dosage. Riddle M. C. et al. Diabetes Care 2014;37:2755-2762

Figure 2—Cumulative mean numbers of confirmed (plasma glucose#3 Figure 2—Cumulative mean numbers of confirmed (plasma glucose#3.9mmol/L [70 mg/dL]) or severe hypoglycemic events per participant during the main 6-month treatment period in the safety population. A: Nocturnal events. B: Events at any time of day or night (24 h). Riddle M. C. et al. Diabetes Care 2014;37:2755-2762

CONCLUSIONS Gla-300 controls HbA1c as well as Gla-100 for people with type 2 diabetes treated with basal and mealtime insulin, but with consistently less risk of nocturnal hypoglycemia Riddle M. C. et al. Diabetes Care 2014;37:2755-2762

Figure 3—RRs of hypoglycemic events at any time of day or night (24 h) or during the night alone (nocturnal) with Gla-300 vs. Gla-100 during 6 months of treatment in the safety population. A: Risk of at least one hypoglycemic event per participant. B: Risk of events per participant-year of exposure. Total participant-year: baseline to month 6: Gla-300, 195 and Gla-100, 193; baseline to week 8: Gla-300, 63 and Gla-100, 62; week 9 to month 6: Gla-300, 132 and Gla-100, 131. 95% CIs are shown. Riddle M. C. et al. Diabetes Care 2014;37:2755-2762

Figure 3—RRs of hypoglycemic events at any time of day or night (24 h) or during the night alone (nocturnal) with Gla-300 vs. Gla-100 during 6 months of treatment in the safety population. A: Risk of at least one hypoglycemic event per participant. B: Risk of events per participant-year of exposure. Total participant-year: baseline to month 6: Gla-300, 195 and Gla-100, 193; baseline to week 8: Gla-300, 63 and Gla-100, 62; week 9 to month 6: Gla-300, 132 and Gla-100, 131. 95% CIs are shown. Riddle M. C. et al. Diabetes Care 2014;37:2755-2762