Combination of Liraglutide and Insulin Degludec

Chicago—According to a randomized, open-label, phase 3 trial, patients with type 2 diabetes who received a combination of liraglutide and insulin degludec had significant reductions in hemoglobin A1c (HbA1c) levels after 26 weeks compared with patients who took either of the treatments alone.

Compared with the insulin degludec-alone group, patients in the combination group also had significant improvements in postprandial glycemic control, a lower risk of hypoglycemia, and no weight gain. In addition, patients in the combination group also had a significant reduction in fasting plasma glucose (FPG) levels and fewer gastrointestinal adverse events compared with the liraglutide-alone group.

John B. Buse, MD, the study’s lead author, presented the results at the ADA meeting in an oral abstract session. Novo Nordisk, manufacturer of insulin degludec and liraglutide, funded the study.

Liraglutide, a long-acting glucagon-like peptide-1 (GLP-1) analog, is FDA approved to be used in combination with diet and exercise for patients with type 2 diabetes. In February 2013, the FDA sent Novo Nordisk a complete response letter regarding insulin degludec, a long-acting basal insulin analog and investigational drug. Before making its decision on approving or rejecting the drug, the agency asked the company for more data from a cardiovascular outcomes trial, which will be completed next year at the earliest.

In this study, the authors randomized 1663 patients in a 2:1:1 ratio to receive the combination of insulin degludec and liraglutide, insulin degludec alone, or liraglutide alone. All patients also received metformin with or without pioglitazone. The treatment period lasted 26 weeks.

Inclusion criteria included patients who had type 2 diabetes, were treatment-naïve, and had an HbA1c level between 7.0% and 10.0% and a body mass index (BMI) of 40 kg/m² or below. The 3 groups were well balanced. Approximately half of patients were males, mean BMI was approximately 31 kg/m², mean duration of diabetes was approximately 7 years, and mean HbA1c level was 8.3%.

After 26 weeks of treatment, patients in the liraglutide-alone group had a mean reduction in HbA1c of 1.28% and an end-of-trial mean HbA1 level of 7.0%; patients in the insulin degludec-alone group had a mean reduction in HbA1c of 1.44% and an end-of-trial mean HbA1 level of 6.9%; and patients in the liraglutide plus insulin degludec group had a mean reduction in HbA1c of 1.91% and an end-of-trial mean HbA1 level of 6.4%. The differences between the combination group compared with each of the monotherapy groups were statistically significant (P<.0001 in both comparisons).

In the combination group, 80.6% of patients had an HbA1c level of ≤7.0% after 26 weeks compared with 65.1% of patients taking insulin degludec alone (P<.0001) and 60.4% of patients taking liraglutide alone (P<.0001). In addition, 69.7% of patients in the combination group had an HbA1c level of ≤6.5% after 26 weeks compared with 47.5% of patients taking insulin degludec alone (P<.0001) and 41.1% of patients taking liraglutide alone (P<.0001).

Further, after 26 weeks of treatment, patients in the liraglutide-alone group had a mean reduction in FPG of 32 mg/dL and an end-of-trial mean FPG of 131 mg/dL, patients in the insulin degludec-alone group had a mean reduction in FPG of 65 mg/dL and an end-of-trial mean FPG of 104 mg/dL, and patients in the liraglutide plus insulin degludec group had a mean reduction in FPG of 65 mg/dL and an end-of-trial mean FPG of 100 mg/dL. The difference between the combination group and the liraglutide monotherapy group was statistically significant (P<.0001), but there was no difference between the combination and insulin degludec monotherapy group.

Adverse events were found in 63.2% of patients in the combination group, 60.2% of patients in the insulin degludec-alone group, and 72.6% of patients in the liraglutide-alone group. Serious adverse events were found in 2.3%, 1.9%, and 3.4% of patients in each of the groups, respectively.