The newer, long-acting basal insulin degludec was noninferior with respect to glycemic control compared with insulin glargine in basal-bolus insulin treatment programs but also resulted in decreased hypoglycemia in patients with type 1 and type 2 diabetes, according to data from two phase 3 studies.
“This is important because hypoglycemia is clearly limiting in the control of type 1 diabetes and is probably limiting in the control of type 2 diabetes as well,” Alan J. Garber, MD, PhD, one of the studies’ researchers and authors, and Endocrine Today Chief Medical Editor, said in an interview. “Additionally, in the type 2 diabetic population, we’ve seen recent evidence that major hypoglycemia is a predictor of excess morbidity and mortality. Therefore, it’s an important safety treatment target that should be minimmized in the management of patients with diabetes.”
Alan J. Garber
Currently available insulin analogues, although an improvement over conventional human insulin, do not necessarily offer complete freedom from hypoglycemia, researchers for the BEGIN Basal-Bolus Type 1 and Type 2 trials said, but the long duration of action and flat, stable pharmacokinetic profile of new compounds such as insulin degludec (Novo Nordisk) show promise.
BEGIN Basal-Bolus Type 1
To evaluate the use of insulin degludec in the management of patients with type 1 diabetes, Simon R. Heller, DM, FRCP, of the University of Sheffield in the United Kingdom, and colleagues conducted an open-label, treat-to-target, noninferiority trial at 79 hospitals and centers in six countries. They randomly assigned 629 adults with type 1 diabetes to insulin degludec or insulin glargine (Lantus, Sanofi-Aventis) in a 3:1 ratio. All patients had been treated with basal-bolus insulin for at least 1 year.
According to study results, patients in the insulin degludec group and those in the insulin glargine group experienced declines in HbA1c of 0.4% and 0.39%, respectively (P<.0001 for noninferiority testing). Further, 40% of the insulin degludec group and 43% of the insulin glargine group achieved the target HbA1c of less than 7%.
Rates of hypoglycemia were also similar, the researchers said, with 42.54 episodes per patient-year occurring in the insulin degludec arm and 40.18 episodes occurring in the insulin glargine arm. The rate of nocturnal hypoglycemia, however, was 25% lower with insulin degludec compared with insulin glargine (4.41 episodes vs. 5.86 episodes). There were also no significant differences in rates of serious adverse events between groups.
In light of their findings, the researchers said insulin degludec potentially represents a better alternative to other basal analogues.
“Insulin degludec might be a useful basal insulin for patients with type 1 diabetes because it provides effective glycemic control while lowering the risk of nocturnal hypoglycemia, which is a major limitation of insulin therapy,” they wrote.
BEGIN Basal-Bolus Type 2
Garber and colleagues conducted a 52-week, open-label, treat-to-target, noninferiority trial to assess insulin degludec in the type 2 diabetes population as well. Their results, he said, were comparable but possibly more striking than those reported in BEGIN Basal-Bolus Type 1 trial.
After 1 year of treatment, the researchers noted a 1.1% decrease in HbA1c among patients assigned insulin degludec and a 1.2% decrease in those assigned insulin glargine, which confirmed noninferiority. Rates of nocturnal hypoglycemia were 25% lower in the insulin degludec group vs. the insulin glargine group (1.4 episodes vs. 1.8 episodes per patient-year of exposure), and overall rates of hypoglycemia were 18% lower (11.1 episodes vs. 13.6 episodes; P<.05 for both). Rates of severe hypoglycemia were too low to assess differences between the two therapies, and there were no differences in other adverse events.
“The significantly lower rate of nocturnal hypoglycemia with insulin degludec while achieving equal glycemic control might offer a safer option in patients with longstanding type 2 diabetes mellitus who need basal-bolus insulin therapy,” the researchers wrote.
Adults with type 2 diabetes and an HbA1c between 7% and 10% after at least 3 months of treatment with any insulin regimen from 123 sites in 12 countries were included in the study. As with the BEGIN Basal-Bolus Type 1 study, they were randomly assigned in a 3:1 ratio.
These data, Garber said, are encouraging.
“What these manuscripts show is that research, ultimately, does lead to improved products that enhance clinical practice,” he said.
“[These studies] show for the first time in a clinical trial setting that the unique pharmacokinetics of insulin degludec indeed produce lower rates of hypoglycemia both overnight and, in the case of type 2 diabetes, around the clock.”
Even so, there are always more targets for investigation.
“We certainly have improved the basal analogues as much as we can at the present time,” Garber said. “However, 80% of the residual hypoglycemia was attributable to the mealtime insulin in the type 2 diabetes study, so we may have to reevaluate mealtime glucose control strategies now.”
Disclosure: Both studies were funded by Novo Nordisk. Dr. Garber has served as a consultant on advisory boards or panels for Boehringer Ingelheim, Daiichi-Sankyo, GlaxoSmithKline, LipoScience, Merck, Novo Nordisk and Takeda, and he has served on speakers’ bureau for Daiichi-Sankyo, GlaxoSmithKline, Merck, Novo Nordisk and Santarus. Dr. Heller has received lecture and consulting fees and research support from Amylin, AstraZeneca, Eli Lilly, Johnson & Johnson, Mannkind, Novo Nordisk, Sanofi and Takeda.