ADA: Degludec and Liraglutide Fixed Combo Shows Continued Efficacy

According to multiple presentations, IDegLira, the fixed combination of insulin degludec and liraglutide, showed long-term efficacy across a range of body mass indices and parameters for type 2 diabetes patients…. 

Stephen C. L. Gough, MD, of the Oxford Centre for Diabetes, Endocrinology & Metabolism presented the extension of a 26-week trial, DUAL 1, which produced sustained benefits at 1 year. DUAL 1 looked at 1,311 patients with type 2 diabetes, who are uncontrolled on oral antihyperglycemic drugs. These patients continued their original 2:1:1 randomization to once-daily combination of insulin degludec and liraglutide (IDegLira, n=665), insulin degludec (n=333) or liraglutide (n=313), plus metformin with or without pioglitazone. According to the results Dr. Gough reported the mean HbA1c in the IDegLira group was reduced from baseline by 1.84%, the insulin degludec group by 1.40%, the liraglutide by 1.21%, which produced 1-year values of 6.4%, 6.9%, and 7.1%, respectively. When it came to achieving an HbA1c of less than 7%, 78.2% of patients on IDegLira achieved this while insulin degludec yielded 62.5%, and liraglutide yielded 56.5%. In regards to the mean fasting plasma glucose, IDegLira and insulin degludec showed similar results, 103 mg/dL and 108 mg/dL, respectively. Unfortunately, liraglutide did not and showed higher mean plasma glucose of 132 mg/dL. By 1 year, IDegLira showed a daily insulin dose, 39U, 37% lower versus insulin degludec, 62U. Furthermore, a 0.4 kg average weight reduction was associated with IDegLira, and had a lower rate of hypoglycemia by 37% when compared to insulin degludec. Additionally, patients experienced fewer GI adverse events with IDegLira when compared with liraglutide (nausea: 10.3% versus 22.3%).

Dr. Gough stated during his presentation, "To conclude, these data demonstrate with 52-week data the sustainability of the glucose-lowering effect and longer-term safety of IDegLira… Compared to insulin degludec, IDegLira was associated with significantly greater reduction in HbA1c, significantly lower risk of hypoglycemia, and no weight gain. While compared to liraglutide, IDegLira was associated with significantly greater reduction in HbA1c, significantly greater reduction in fasting plasma glucose and fewer gastrointestinal adverse events."

In regards to BMI categories, John B. Buse, MD, PhD, from the division of endocrinology and metabolism at the University of North Carolina School of Medicine, presented post-hoc analysis from both the DUAL 1 and DUAL 2 studies. Both DUAL 1 and DUAL 2 studies looked at patients uncontrolled on basal insulin and oral antihyperglycemic drugs, in better efforts to determine whether IDegLira was effective across the range of baseline BMI categories.

In the DUAL 1 study, the HbA1c reduction was 1.8-1.9% seen with IDegLira, and showed the baseline BMI to be independent. According to each BMI category, the IDegLira presented a greater decrease in HbA1c when compared with insulin degludec or liraglutide both of which yielded a P<0.001. The DUAL 2 showed a HbA1c reduction of 1.6-2.1% with IDegLira, and a great reduction in BMI of 30-35 kilogram per meters squared. Patients on IDegLira, 33.1%, reached a target HbA1c of less than seven percent, in addition to weight loss and no hypoglycemia reported, while 39.2% of patients achieved the same in DUAL 2. Dr. Buse stated, "Across all BMI categories, IDegLira improved glycemic control with a low risk of hypoglycemia…. Insulin requirements were reduced with IDegLira compared with insulin degludec alone across all four BMI categories in the DUAL 1 extension."

Helena W. Rodbard, MD, FACP, MACE, who is in private practice in Maryland, presented a post-hoc analysis of both DUAL 1 and DUAL 2. According to Dr. Rodbard, both showed efficacy of IDegLira in patients with type 2 diabetes, in regards to HbA1c, diabetes duration, and insulin dose. Dr. Rodbard stated, in DUAL 1, IDegLira showed greater HbA1c reductions of 1.1-2.5% when compared with insulin degludec or liraglutide in four baseline HbA1c categories. Additionally, in DUAL 2, Dr. Rodbard showed similar results. She stated, "In the DUAL 1, patients with a higher baseline HbA1c category saw greater reductions with IDegLira (P<0.0001), and HbA1c reduction was independent of diabetes duration."

Practice Pearls:

• IDegLira, the fixed combination of insulin degludec and liraglutide, showed long-term efficacy across a range of body mass indices and parameters.
• Compared to insulin degludec, IDegLira was associated with significantly greater reduction in HbA1c, significantly lower risk of hypoglycemia and no weight gain.
• Across all BMI categories, IDegLira improved glycemic control with a low risk of hypoglycemia

Presented at: American Diabetes Association’s 74th Scientific Sessions, June 2014. Gough SCL. Abstract 65-OR. Buse JB. Abstract 66-OR. Rodbard HW. Abstract 67-OR.