Efficacy and Safety of IDegLira in Patients with Type 2 Diabetes Maintained After 1 Year of Treatment

Professor Stephen CL Gough, MD, of the Oxford Centre for Diabetes, Endocrinology, and Metabolism, UK, presented information on a 26-week follow-up to a Phase 3 multinational, multicenter study monitoring efficacy and safety data for treatment of type 2 diabetes patients with IDegLira, a combination of insulin degludec (IDeg) and liraglutide.

Gough presented these results at a session Saturday at the American Diabetes Association’s 74th Scientific Sessions, held June 13-17, 2014, in San Francisco, CA.

Gough began his talk by saying that “the roles of basal insulin and glucagon-like peptide-1 (GLP-1) receptor agonists are well established in the management of type 2 diabetes. We can titrate in an individualized way the dose of insulin and successfully reduce blood glucose. We do so, however, with an increased risk of hypoglycemia and also weight gain.”

“We know that GLP-1 receptor agonists can reduce fasting and post-prandial glucose and, because of the glucose-dependent mechanism of action, that this is associated with a lowered risk of hypoglycemia. We often see weight reduction, as well. While these agents are associated with an increased risk of gastrointestinal side effects, there is increasing evidence that when we use these two classes of drugs together we can improve both fasting and post-prandial glucose along with a lower rate of hypoglycemia and less weight gain. We also see fewer gastrointestinal side effects than if we used GLP-1 receptor agonists alone,” said Gough.

IDegLira, a combination of insulin degludec (IDeg) and liraglutide, had previously been seen in a 26-week trial to provide the advantages of each component while mitigating the main side effects of each component. In an extension to that study, participants continued their allotted treatment in a 3-arm trial in which they were randomized 2:1:1 to receive once-daily IDegLira or one of its components, plus metformin ± pioglitazone. The 26-week extension examined whether the benefits of IDegLira were sustained. Gough reported that IDegLira was able to maintain the glucose-lowering effects after an additional 26 weeks and confirmed safety evaluations.

IDegLira and IDeg were titrated to a fasting plasma glucose (FPG) level of 72-90 mg/dL. Of 1,663 adults randomized in the main trial (mean age: 55 yrs; BMI: 31.2 kg/m²), 1,311 (78.8%) of them entered the extension, with 665 patients continuing on IDegLira, 333 on IDeg, and 313 on liraglutide. Percentage of participants remaining in each cohort amounted to 79.7%, 80.4%, and 75.4%, respectively, compared with the number originally randomized.

Analysis of the data showed that mean HbA1c was reduced 1.8% from baseline by IDegLira, 1.4% by IDeg, and 1.2% by liraglutide. End of trial mean HbA1c values were 6.4%, 6.9% and 7.1%, respectively; 78% of patients on IDegLira achieved an HbA1c value of 7% or less, versus 63% of patients for IDeg and 57% for liraglutide.

Mean fasting plasma glucose values were similar for IDegLira (103 mg/dL) and IDeg alone (108 mg/dL) but were higher for liraglutide alone (132 mg/dL). By the end of the study, the daily insulin dose with IDegLira was 39 U, 37% lower than IDeg (62 U). IDegLira had a 37% lower rate of hypoglycemia compared with IDeg, and fewer patients had gastrointestinal adverse events with IDegLira vs. liraglutide (nausea: 10.3% vs. 22.3%).

In conclusion, regarding the results of the extension trial, Gough stated, “Compared to degludec, IDegLira was associated with significant reductions in HbA1c, lower risk of hypoglycemia, and no weight gain at 52 weeks. Compared to liraglutide, IDegLira was associated with a significantly greater reduction in HbA1c, significantly greater reduction in fasting plasma glucose, and fewer gastrointestinal adverse events. These data demonstrate and further support the sustainability of the glucose-lowering effect and long-term safety of IDegLira.”