CHICAGO – A new longer-acting basal insulin glargine formulation was as effective as the familiar insulin glargine 100 U/mL/Lantus in controlling glycemia while producing a 21% lower rate of severe nocturnal hypoglycemic events in the phase III EDITION I trial.
The investigational formulation contains insulin glargine 300 U/mL and is known as U300. Like insulin glargine U100, the investigational agent is a once-daily, long-acting insulin analog. But U300 has an even flatter, longer, and more stable pharmacodynamic profile, which translates into a lower risk of hypoglycemia, as shown in the EDITION I trial, principal investigator Dr. Matthew C. Riddle explained at the annual scientific sessions of the American Diabetes Association.
Bruce Jancin/IMNG Medical Media
Dr. Matthew Riddle (center) fields questions about the EDITION I trial.
EDITION I included 807 adults with type 2 diabetes who were on an established treatment with at least 42 U/day of basal glargine or NPH along with mealtime insulin with or without metformin. Their mean duration of diabetes was 15.8 years, and their mean body mass index was 36.6 kg/m2. They were randomized to 6 months of open-label insulin glargine U300 or insulin glargine U100 once daily in the evening while continuing on their mealtime insulin. The basal insulin was titrated to achieve a fasting plasma glucose of 80-100 mg/dL.
The primary efficacy endpoint was change in hemoglobin A1c from baseline through month 6. The reductions were the same in both groups: a mean decrease of 0.83%.
The chief secondary endpoint was the occurrence of one or more episodes of severe and/or confirmed nocturnal hypoglycemia to a level of 70 mg/dL or less during months 3-6. The rate was 36.1% in the U300 group, compared with 46% with U100, for a highly significant 21% risk reduction, said Dr. Riddle, professor of medicine at the Oregon Health and Science Center, Portland.
Any nocturnal hypoglycemia during the 6-month study occurred in 45.3% of patients on U300 vs. 59.7% on U100, for a 24% relative risk reduction, he added.
EDITION I is the first in a large worldwide series of phase III trials of the investigational insulin. The recently completed EDITION II trial replicated the EDITION I findings blood glucose reductions similar to those seen in patients taking Lantus, with fewer serious nocturnal hypoglycemic events – in 811 type 2 diabetic patients with earlier-stage disease as evidenced by the enrollment requirement that they be established on basal insulin and oral antidiabetic therapy. EDITION III is ongoing in insulin-naive type 2 diabetic patients, EDITION IV focuses on patients with type 1 diabetes, and EDITION JP I and II are ongoing in Japan. These trials are designed to assess the relative performance of U100 and the investigational insulin in a range of common clinical scenarios.
"The question is what proportion of patients is going to have a clinically relevant difference in success with the new formulation versus the old one. I don’t know the answer to that yet," Dr. Riddle said in an interview. "U100 has been a really successful insulin, and the likelihood of it going away is really, really low. We’ll probably end up dividing the basal insulin patients into a good many continuing on Lantus U100, and a good many others using newer, longer-acting insulins, U300 being one, but not the only one. When affordability is an issue, taking any insulin is better than not taking it at all."
Dr. Riddle receives research grant support from and is paid consultant to several pharmaceutical companies, among them Sanofi, which sponsors the EDITION trials.