This article is more than 5 years old. Information may no longer be current.
Degludec, liraglutide fixed combination shows continued efficacy in trio of studies
SAN FRANCISCO — The fixed combination of insulin degludec and liraglutide, known as IDegLira, showed longer-term efficacy across a range of body mass indices and parameters of type 2 diabetes, according to three presentations at the American Diabetes Association’s 74th Scientific Sessions.
“To conclude, these data demonstrate with 52-week data the sustainability of the glucose-lowering effect and longer-term safety of IDegLira,” Stephen C. L. Gough, MD, of the Oxford Centre for Diabetes, Endocrinology & Metabolism, said during his presentation. “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.”
Gough presented the extension of DUAL 1, originally a 26-week trial that showed positive results; the extension produced sustained benefits at 1 year.
The data presented looked at 1,311 patients with type 2 diabetes uncontrolled on oral antihyperglycemic drugs who were continuing their original 2:1:1 randomization to once-daily combination of insulin degludec and liraglutide (IDegLira, n=665), insulin degludec (n=333) or liraglutide (1.8 mg, n=313), plus metformin with or without pioglitazone.
Gough reported that mean HbA1C was reduced from baseline by 1.84% in the IDegLira group, 1.40% in the insulin degludec group and 1.21% and liraglutide, producing 1-year values of 6.4%, 6.9% and 7.1%, respectively.
Of the patients on IDegLira, 78.2% achieved an HbA1C of less than 7% vs. 62.5% for insulin degludec and 56.5% for liraglutide. Mean fasting plasma glucose was similar for IDegLira (103 mg/dL) and insulin degludec (108 mg/dL), but higher for liraglutide (132 mg/dL). At 1 year, daily insulin dose was 37% lower with IDegLira (39 U) vs. insulin degludec (62 U).
Additionally, IDegLira was associated with an average weight reduction of 0.4 kg, and had a 37% lower rate of hypoglycemia vs. insulin degludec, Gough said. Fewer patients had GI adverse events with IDegLira vs. liraglutide (nausea: 10.3% vs. 22.3%).
Support across 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 DUAL 1 and DUAL 2, a study looking at patients uncontrolled on basal insulin and oral antihyperglycemic drugs. This analysis sought to determine if IDegLira was effective across the range of baseline BMI categories.
In DUAL 1, the reduction of HbA1c by IDegLira was 1.8-1.9% and was independent of baseline BMI. In each BMI category, the IDegLira group showed a greater decrease in HbA1c vs. insulin degludec or liraglutide (both P<0.001). In DUAL 2, IDegLira showed a reduction of HbA1c of 1.6-2.1%, with the greatest reduction in the BMI category of 30-35 kg/m2.
In DUAL 1, 33.1% of patients on IDegLira reached a target HbA1c of <7% with weight loss and no hypoglycemia, while 39.2% of patients on IDegLira achieved the same in DUAL 2.
“Across all BMI categories, IDegLira improved glycemic control with a low risk of hypoglycemia,” Buse said. “Insulin requirements were reduced with IDegLira compared with insulin degludec alone across all four BMI categories in the DUAL 1 extension.”
Support across the range of diabetes
Helena W. Rodbard, MD, FACP, MACE, who is in private practice in Maryland, presented a post-hoc analysis of both studies as well, showing efficacy of IDegLira across three parameters of type 2 diabetes: HbA1c, diabetes duration and insulin dose.
In DUAL 1, IDegLira produced greater HbA1c reductions (1.1-2.5%, P<.01) in comparison with insulin degludec or liraglutide in four baseline HbA1c categories (≤7.5; >7.5-≤8.5; 8.5-≤9.0; >9.0). Rodbard showed similar results from DUAL 2 (0.9-2.5%). In DUAL 1, patients with higher baseline HbA1c category saw greater HbA1c reductions with IDegLira (P<.0001), and HbA1c reduction was independent of diabetes duration, Rodbard said.
“IDegLira is efficacious across baseline glycemic control, duration of diabetes and prior use of anti-diabetic medications,” Rodbard said. “IDegLira lowers HbA1c well into the target range and rates of hypoglycemia with IDegLira are low for the degree of glycemic control achieved.”
For More Information:
Gough SCL. Abstract 65-OR. Presented at: American Diabetes Association’s 74th Scientific Sessions; June 13-17, 2014; San Francisco.
Buse JB. Abstract 66-OR. Presented at: American Diabetes Association’s 74th Scientific Sessions; June 13-17, 2014; San Francisco.
Rodbard HW. Abstract 67-OR. Presented at: American Diabetes Association’s 74th Scientific Sessions; June 13-17, 2014; San Francisco.
Disclosures: These studies were sponsored by Novo Nordisk. The presenters have financial relationships with Novo Nordisk and other manufacturers.
Perspective
Back to Top
Studies that have used these two classes together have been uniformly encouraging because they do show that you have less weight gain when insulin is used together with a GLP-1 receptor agonist and, in some cases, you get better overall glucose control.
The disadvantage, of course, is that you get potential side effects from the GLP-1 receptor agonists that you don’t get with insulin, so you get some gains and losses. Overall, the balance looks very favorable. This is another in a series of studies that shows that this an attractive combination for the future.
How we are going to use them and in what patients is still in question.
We have learned a lot about how to use basal insulin in clinical practice the past 10 years and much of it has come from the development of new drugs because the manufacturers conduct very carefully done and interesting clinical studies. We learn from them both the things that the manufacturers are interested in — which is that the drugs are safe and effective and can be approved and used — but they also teach us about subgroups of patients and how to adjust dosing and how to use the drugs clinically.
Every time we have a new round of studies presented like this, it teaches us that much more about the clinical application of the treatment. That’s absolutely true for the basal insulins. It’s absolutely true for the combination basal insulin with the GLP-1 receptor agonist and that’s very interesting data on the fixed combination. It’s what we would expect, but it’s encouraging and the subgroup analyses are helpful clinically to doctors.