Patients treated with a new, more concentrated insulin glargine formulation experienced similar glycemic control with fewer nocturnal and daytime hypoglycemic events compared with patients treated with the current formulation of the product.
Geremia B. Bolli, MD, Professor of Endocrinology at the University of Perugia, Italy, presented results from EDITION 3, a Phase 3 trial that compared Gla-300, a new formulation of glargine at 300 U/mL, with Gla-100, glargine at 100 U/mL, the glargine formulation already marketed by Sanofi-Aventis as Lantus. The Gla-300 formulation is intended to provide a more constant and prolonged pharmacokinetic response. Bolli spoke at a session Saturday at the American Diabetes Association’s 74th Scientific Sessions, held June 13-17, 2014, in San Francisco, CA.
The main objective of the study was to establish efficacy and safety of Gla-300 compared with Gla-100 in patients with type 2 diabetes (T2DM) insufficiently controlled by oral anti-diabetic drugs (OADs), over 6 months of treatment. “The primary endpoint was non-inferiority as assessed by no difference in HbA1C by the end of the study,” said Bolli. In addition to establishing non-inferiority of Gla-300 to Gla-100 in terms of HbA1C reduction, protection against the risk of hypoglycemia was also a key factor.
Bolli said, “An important main secondary endpoint was the percentage of participants with one or more events of hypoglycemia from week 9 to month 6 of the study.”
Nocturnal hypoglycemia was a particular focus. The full results from the EDITION 3 trial showed that significantly fewer patients experienced low blood sugar events during the night over the study period when treated with GLA-300 compared with GLA-100.
Bolli, the principal investigator of the study, said, “Low blood sugar events at any time of the day or night should not be underestimated, particularly for those who are starting out with a new or alternate insulin therapy. As it is well known in clinical practice, many people go through a sensitive phase when starting insulin, and they tend to drop the treatment or not properly up-titrate when exposed to low blood sugar events. Reducing low blood sugar events in this particular phase of treatment is relevant in helping patients better manage diabetes.”
In this 6-month, multicenter, open-label study, nearly 900 insulin-naïve participants with mean BMI of 33 kg/m2, mean type 2 diabetes duration of 9.8 years, and mean HbA1c of 8.5 % were randomized 1:1 to once-daily Gla-300 or Gla-100, administered in the evening. Oral antihyperglycemic medications were maintained, with the exception of sulfonylureas. Insulin was titrated to the goal of a fasting plasma glucose (FPG) level between 4.4 and 5.6 mmol/L.
The primary endpoint, the observed change in HbA1c level to month 6, was assigned a non-inferiority margin of 0.4% points HbA1c level. The main secondary endpoint, the percentage of participants with ≥1 confirmed ≤70 mg/dL (≤3.9 mmol/L) or severe nocturnal hypoglycemic event from week 9 to month 6, followed the titration phase across the first 8 weeks of the study. A more pronounced but not significant numerical reduction of hypoglycemic event rates was observed during the first 8 weeks.
The response rate (RR) of experiencing any confirmed or severe nocturnal hypoglycemia with Gla-300 vs. Gla-100 was 0.76 [CI: 0.59 to 0.99] for the 6-month treatment, 0.74 [CI: 0.48 to 1.13] for 0 to 8 weeks, and 0.89 [CI: 0.66 to 1.20], p=0.45, for week 9 to month 6. The benefit of Gla-300 in terms of confirmed ≤70 mg/dL or severe hypoglycemia extended beyond the predefined nocturnal period of midnight to 6:00am, as a consistent reduction across the hypoglycemic definitions was observed, including any time of day confirmed or severe and documented symptomatic events. Response rates (per patient-year) of all confirmed or severe events at any time were lower with Gla-300 (RR 0.75 [CI: 0.57 to 0.99]) over 6 months. Severe hypoglycemia was infrequent.
Bolli summarized the results by saying that in insulin-naive patients with type 2 diabetes and in the absence of sulfonylureas, Gla-300 demonstrated improvements in glycemic control comparable with those of Gla-100 and with a lower risk of hypoglycemia, with fewer participants reporting ≥1 nocturnal confirmed instance of HbA1c ≤70 mg/dL or other severe hypoglycemic event from week 9 to month 6.