VIENNA – A hemoglobin A1c of less than 7% was achieved by 78% patients with type 2 diabetes when insulin degludec (IDeg) was added to oral antidiabetic drug therapy in a randomized, double blind, phase III study.
In comparison, 36% of patients treated with the glucagon-like peptide 1 (GLP-1) agonist liraglutide (Victoza, Novo Nordisk) on top of metformin achieved this blood glucose target, with an odds ratio favoring treatment intensification of 7.79.
Furthermore, after about 6 months of treatment, HbA1c was 0.92% lower in the insulin-added arm than in the control arm, with mean end-of-treatment values of 6.5% versus 7.5% (P < .0001), respectively.
“This treatment approach also resulted in lower fasting plasma glucose [FPG] … and overall low rates of hypoglycemia,” Dr. Vanita Aroda of MedStar Health Research Institute in Hyattsville, Md., said at the annual meeting of the European Association for the Study of Diabetes.
IDeg (Tresiba, Novo Nordisk) is an ultra-long-acting basal insulin analogue currently approved for use in Europe and some other countries around the world. A dual, once-daily, single-injection formulation of IDeg and liraglutide (Xultophy, Novo Nordisk) also is under investigation.
Results from the DUAL (Dual Action of Liraglutide and Insulin Degludec in Type 2 Diabetes) program with the fixed dose combination were reported elsewhere at the EASD annual meeting and recently reported (Lancet Diabetes Endocrinol. 2014 Sept. 2 [doi:10.1016/S2213-8587(14)70174-3]).
In the present study, Dr. Aroda and her associates aimed to confirm the efficacy and safety of IDeg given separately but in combination with liraglutide and metformin versus these oral antidiabetic drugs (OADs) plus an injected insulin placebo.
Dr. Julio Rosenstock
A total of 1,504 patients with diabetes of at least 6 months’ duration, being treated with metformin or other OADs but not insulin, and in need of treatment intensification were screen for possible inclusion in the trial.
After a 15-week run-in period, during which time the dose of liraglutide was titrated up to 1.5 mg, 346 patients were randomized to receive liraglutide plus metformin and either IDeg or an injectable placebo.
Ninety-two percent of the 174 patients randomized to IDeg plus liraglutide and metformin completed the 26-week trial, as did 76% of the 172 randomized to the placebo arm. Baseline characteristics of the two groups of patients were similar, with a mean age of 57 years, 9 years’ diabetes duration, and a starting HbA1c of about 7.5%.
FPG values at baseline were 8.7 mmol/L in the intensified arm and 9.1 mmol/L in the placebo arm. These decreased to 8.8 and 6.1 mmol/L, respectively, with an end-of-treatment difference of –2.55 mmol/L favoring the intensified arm, a highly significant difference.
Daily insulin doses at the end of treatment were 51 units in the intensified arm and the equivalent of 105 units in the placebo arm.
Mean body weight was lower in the IDeg-supplemented arm than in the placebo arm at baseline (90.7 kg vs. 94.2 kg), and there was an average weight gain of 2 kg and weight loss of 1.3 kg in each arm, respectively, over the study period, such that the mean body weight at the end of the trial was the same, at 92.7 kg.
No cases of severe hypoglycemia were reported, and there was no significant difference in the number of confirmed nocturnal hypoglycemia cases (four events in three patients with IDeg versus two events in two patients with placebo). The rate of confirmed hypoglycemia was significantly higher in insulin-treated patients (17.3% vs 4.7%); otherwise, both regimens studied were well tolerated.
Dr. Julio Rosenstock of Dallas Diabetes & Endocrine Center, who chaired the session, said that these results were “impressive” and that the study was much better designed than was a similar study with insulin detemir (Levemir, Novo Nordisk) added to liraglutide.
“This is better because you have a control injectable,” he said. “In the previous study with detemir the A1c came down to 7.1% after 6 months, as reported by DeVries [Diabetes Care 2012;35:1446-54], and to 7.2%, as we reported, after 1 year [J. Diabetes Complications 2013;27:492-500].
“In that previous study the dose of detemir was 39 units, here it was 51 units, so the question is, are the better results because of a higher insulin dose, or because of a difference in the insulin?”
Dr. Rosenstock suggested that a head-to-head trial of insulin detemir and IDeg would be needed to determine the answer. Dr. Aroda agreed.
Dr. Aroda and Dr. Rosenstock disclosed ties with Novo Nordisk, which funded the study, and with other companies that manufacture diabetes medications and devices.