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Insulin degludec/liraglutide combo improved glucose in type 2 diabetes
A fixed-dose combination of insulin degludec and liraglutide improved plasma glucose for patients with type 2 diabetes who had not achieved glycemic control with oral antidiabetic drugs alone or combined with basil insulin, according to a presenter at the 50th European Association for the Study of Diabetes Annual Meeting.
“Insulin degludec/liraglutide combination treatment resulted in a greater proportion of subjects with blood glucose values within target ranges vs. the individual components in insulin degludec or liraglutide for all pre- and all postprandial values,” Allen King, MD, FACP, FACE, CDE, co-founder of the Diabetes Care Center in Salinas, Calif., said.
King and colleagues from other institutions conducted a post-hoc analysis of two phase 3 trials: DUAL I (n=1,663) compared combined insulin degludec/liraglutide (IDegLira; Novo Nordisk) vs. insulin degludec and liraglutide in patients uncontrolled on oral antidiabetic drugs for 52 weeks; and DUAL II (n=398) compared IDegLira vs. insulin degludec in patients uncontrolled on basal insulin and oral antidiabetic drugs for 26 weeks. Patients had similar baseline blood glucose values across both trials.
The researchers investigated the proportion of patients with self-measured blood glucose values, at the end of the trials, within preprandial target range (≥3.9 mmol/L to ≤7.2 mmol/L) and postprandial target range (<9 mmol/L) with IDegLira compared with insulin degludec or liraglutide alone.
Preprandial values were assessed before breakfast, lunch, dinner and at breakfast the following day. Postprandial values were assessed 90 minutes after breakfast, lunch and dinner. Measurements before bedtime and at 4 a.m. created a full nine-point profile; the researchers compared the proportion of patients demonstrating a nine-point profile between ≥3.9 mmol/L and <9 mmol/L with IDegLira and insulin degludec or liraglutide alone.
The likelihood of patients achieving all four preprandial values within the recommended range was significantly greater with IDegLira compared with insulin degludec (DUAL I: 48% vs. 41%, P=.0204; DUAL II: 44% vs. 27%, P=.0008) and liraglutide (48% vs. 32%, P=.0001).
The proportion of patients reaching all three postprandial values was significantly higher for patients treated with IDegLira than those treated with insulin degludec (DUAL I: 51% vs. 38%, P<.0001; DUAL II: 37% vs. 25%, P=.0093) and liraglutide (51% vs. 36%, P<.0001).
The proportion of patients with all nine values within range was significantly higher with IDegLira compared with insulin degludec (DUAL I: 39% vs. 28%, P<.0001; DUAL II: 32% vs. 20%, P=.0067) and liraglutide (39% vs. 31%, P=.0059).
“The reduction in the glucose range over 24 hours was significantly greater with IDegLira vs. [insulin degludec],” King said. “These data support the findings of the main trials with greater glycemic control afforded with, or by, IDegLira vs. [insulin degludec] or [liraglutide] alone and without an increased risk of hypoglycemia with [insulin degludec].”
For more information:
King A. Abstract #243. Presented at: 50th EASD Annual Meeting; Sept. 16-19, 2014; Vienna.
Disclosure: The study was supported by Novo Nordisk. King reports being a speaker and consultant for, as well as receiving research funding from, several industry companies, including Novo Nordisk.
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This study looked at the impact of treatment with a combination of degludec and liraglutide in type 2 diabetes, versus using each drug alone. It is very nicely done. The most remarkable thing was that the combination treatment lead to a greater reduction in HbA1c and that this reduction was more than one HbA1c point. It is hard to get this much lowering with any agent, so it’s very exciting that they could accomplish this, especially with neutral effect on weight gain.
The authors were particularly interested in looking at glucose variability during the day during treatment with the combination or either drug alone. While it may be an important point, and it’s interesting that less variability was seen with the combination, we know that clinical outcomes are linked to HbA1c, and we don’t know the relationship between long-term clinical outcomes and variability.
This study used degludec, a basal insulin not available in the United States. It is possible it has some advantages over some other basal insulins. Aside from that, however, just combining a basal insulin with a glucagon like peptide-1 (GLP-1) agonist may provide us better coverage both pre-meal and post-meal than we can get with either one alone. Using a once-a-day GLP-1 in a single formulation with a basal insulin or a longer-acting GLP-1 agonist with daily insulin may be simpler for patients to use than current formulations.