IDegLira trumps insulin glargine in maintaining glycaemic control for T2D
Using insulin degludec combined with liraglutide (IDegLira) as initial injectable therapy in patients with type 2 diabetes (T2D) who were uncontrolled on oral antidiabetic drugs significantly delays the need for treatment intensification compared with insulin glargine 100 U/mL (IGlar U100) alone, the DUAL VIII study shows.
“IDegLira showed greater durability than IGlar U100, in reaching and maintaining patients at glycaemic goals for longer, thereby minimizing the need for additional therapy, while also reducing the side effects often associated with insulin-only therapy,” according to the investigators led by Dr Vanita Aroda from the Brigham and Women’s Hospital in Boston, Massachusetts, US.
Although current guidelines recommend sequential treatment escalation based on achievement of HbA1c goals and individual needs, many patients often do not reach their glycaemic targets in real-world practice due to clinical inertia – which refers to failure to set appropriate targets and intensify treatment to achieve treatment goals.
“A key driver of clinical inertia in T2D is the challenge of adding to the existing polypharmacy of patients. Weight gain and hypoglycaemia are also two major concerns for patients and healthcare professionals when initiating insulin therapy,” stated the investigators.
Therefore, it is of interest to find out whether one approach is more effective than the other in helping patients to attain and maintain their treatment goals over the long term, said Aroda.
Durable control with IDegLira
The multinational, open-label, phase IIIb trial involved 1,012 insulin-naïve patients (mean age 56 years) with T2D who were eligible for basal insulin intensification (HbA1c, 7.0–11.0 percent [mean, 8.5 percent], mean fasting plasma glucose [FPG], 10 mmol/L, mean diabetes duration of 10 years). They were randomized 1:1 to receive IDegLira or IGlar U100, both in a 3 mL prefilled pen for once-daily subcutaneous injection in addition to existing antidiabetic medication. [Lancet Diabetes Endocrinol 2019;doi:10.1016/S2213-8587(19)30184-6]
IDegLira is a fixed-ratio combination of 100 units/mL long-acting basal insulin degludec and 3.6 mg/mL of the GLP-1* receptor agonist (RA) liraglutide in a single pen.
The primary endpoint of time to treatment intensification was significantly longer in the IDegLira group than the IGlar U100 group (median, >2 years vs ~1 year; p<0.0001). Over 104 weeks of treatment, fewer patients who received IDegLira vs IGlar U100 required treatment intensification (37 percent vs 66 percent), defined as HbA1c ≥7.0 percent at two consecutive visits.
In addition, among patients who did not need to intensify treatment, patients treated with IDegLira were significantly more likely than those taking IGlar U100 to achieve HbA1c <7.0 percent without weight gain and/or hypoglycaemia, both which are known to contribute to clinical inertia.
“The greater durability seen with IDegLira might be related to the ability to target both fasting and postprandial hyperglycaemia compared with the use of basal insulin alone,” suggested the investigators.
Compared with IGlar U100, IDegLira led to improved SMBG** and FPG (p=0.001) over 104 weeks. Weight gain (p<0.0001), severe or blood glucose-confirmed symptomatic hypoglycaemia (p<0.0001), and insulin requirement (p<0.0001) were also less common in the IDegLira arm compared with the IGlar U100 arm.
According to Aroda and co-authors, degludec and liraglutide have complementary mode of actions in addressing the distinct abnormalities of T2D. “Basal insulins are effective at lowering HbA1c and FPG, whereas liraglutide reduces FPG and postprandial glucose in a glucose-dependent manner,” they explained.
“IDegLira showed improved outcomes compared with basal insulin alone, without the need for separate insulin and GLP-1 RA injections,” observed Aroda and co-authors. “Initiating IDegLira might help reduce clinical inertia by helping to overcome the main barriers of achieving good glycaemic control when initiating insulin therapy.”
There were no new safety signals or treatment-related deaths.
In an accompanying commentary, nonetheless, the lack of a GLP-1 RA-only comparator group was noted by Dr Srikanth Bellary and colleagues from University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK who wrote that “a valuable opportunity to provide a more definitive answer regarding the relative merits of all three of these options has been missed.” [Lancet Diabetes Endocrinol 2019;doi:10.1016/S2213-8587(19)30198-6]
“Such a comparison between IDegLira and a GLP-1 RA could be considered even more relevant given the latest ADA*** and EASD# guidelines, which recommend GLP-1RAs as the first injectable drug for most patients and as the preferred second-line treatment after metformin in those with atherosclerotic cardiovascular disease,” they explained.
Bellary and colleagues also called for individualization of treatment when choosing among the three options, taking into consideration “issues such as patient preference, cardiovascular disease status, potential for side effects, and glycaemic control.”