This is the first in a series of studies to determine whether the longer, flatter action profile of U300 insulin glargine (vs U100 glargine) will result in less hypoglycemia, and especially nocturnal events.
People with type 2 diabetes mellitus (T2DM) who require basal and mealtime insulin have less risk of nocturnal hypoglycemia with investigational glargine-300 (Gla-300; Sanofi) than with glargine-100 (Gla-100; Lantus [Sanofi]), according to results from the multinational EDITION-1 study published in October 2014 in Diabetes Care. Glycemic control achieved in the study was similar for the two agents.
“EDITION 1 is the first of a series of studies being done to learn whether the longer and flatter profile of action of U300 glargine, compared to U100 glargine, will lead to less hypoglycemia or other clinical benefits,” commented first author Matthew Riddle, MD, who is head of Oregon Health Sciences University’s Section of Diabetes.
“The patients in this study were selected for having T2DM that needs both basal and mealtime insulin, and for requiring high insulin doses,” Riddle said. “Such people often struggle with glucose control, and it’s reassuring that the study showed they had less tendency toward hypoglycemia at night with the new form of insulin glargine.”
The phase 3 multinational study (13 countries) used a 6-month open-label, parallel-group design and took place between December 2011 and January 2013. Participants had T2DM not adequately controlled on daily basal insulin (at least 42 units per day of NPH or glargine) and mealtime insulin (insulin lispro, aspart, glulisine).
Participants were randomized to receive once daily Gla-300 (n=404) or Gla-100 (n=403). Doses were titrated to a fasting glucose goal of between 4.4 and 5.6 mmol/L. Timing and number of basal insulin dosage adjustments followed a predefined protocol. Mealtime insulin dose adjustments were left up to the investigator, following optimization of basal insulin.
Participants had a mean age of 60 years, mean diabetes duration of 16 years, mean BMI of 36.6 kg/m2, and mean A1c of 8.15%. Both groups had similar reductions in A1c. At the end of treatment, A1c was 7.25% in the Gla-300 group and 7.28% in the Gla-100 group. About 40% of participants in the Gla-300 group and 41% in the GLa-100 group met A1c targets of <7.0%. The least squares mean difference met the criteria for noninferiority of Gla-300 compared with Gla-100 (-0.00% [95% CI, -0.11 to 0.11]; -0.00 mmol/mol [-1.2 to 1.2]).
Participants in the Gla-300 group had fewer confirmed (≤3.9 mmol/L) or severe nighttime hypoglycemia episodes between week 9 and month 6, compared with those in the Gla-100 group (36% vs 46%, respectively; P<.005). Compared with the Gla-100 group, the Gla-300 group had a 10% absolute and 21% relative risk reduction for having at least one confirmed or severe nocturnal hypoglycemic event from week 9 to month 6.
Both groups experienced a 0.9-kg increase in body weight. Tolerability and safety were similar between groups. Serious treatment-related adverse events occurred in 6.4% of the Gla-300 group and 5.2% of the Gla-100 group. Two cases of hypoglycemic coma occurred in the Gla-300 group.
“U300 glargine contains the same insulin molecule as U100 glargine, so it would be surprising if any new safety issues appeared,” Riddle pointed out.
“Which people with diabetes may have the greatest reduction of hypoglycemia with the new glargine is likely to become apparent when the rest of the EDITION studies are completed and analyzed,” Riddle emphasized. “Study of U100 glargine in the past 10 years has taught us and our patients a great deal about how to use basal insulin in clinical practice, and I expect ongoing studies of U300 glargine will continue to help us with this.”
The study was sponsored by Sanofi, the maker of Gla-100 and Gla-300. Sanofi designed, coordinated, monitored clinical sites, collected and managed the data, and performed the statistical analyses.