A New-Generation Ultra-Long-Acting Basal Insulin With a Bolus Boost Compared With Insulin Glargine in Insulin-Naïve People With Type 2 Diabetes

Abstract

OBJECTIVEInsulin degludec/insulin aspart (IDegAsp) is a soluble coformulation of the novel basal analog insulin degludec (IDeg: 70%) and insulin aspart (IAsp: 30%). We compared the safety and efficacy of IDegAsp, an alternative formulation (AF) (55% IDeg and 45% IAsp), and insulin glargine (IGlar) in insulin-naïve subjects with type 2 diabetes inadequately controlled with oral antidiabetic drugs.RESEARCH DESIGN AND METHODSIn this 16-week, open-label trial, subjects (mean age 59.1 years, A1C 8.5%, BMI 30.3 kg/m2) were randomized to once-daily IDegAsp (n = 59), AF (n = 59), or IGlar (n = 60), all in combination with metformin. Insulin was administered before the evening meal and dose-titrated to a fasting plasma glucose (FPG) target of 4.0–6.0 mmol/L.RESULTSAfter 16 weeks, mean A1C decreased in all groups to comparable levels (IDegAsp: 7.0%; AF: 7.2%; IGlar: 7.1%). A similar proportion of subjects achieved A1C <7.0% without confirmed hypoglycemia in the last 4 weeks of treatment (IDegAsp: 51%; AF: 47%; IGlar: 50%). Mean 2-h postdinner plasma glucose increase was lower for IDegAsp (0.13 mmol/L) and AF (0.24 mmol/L) than IGlar (1.63 mmol/L), whereas mean FPG was similar (IDegAsp: 6.8 mmol/L; AF: 7.4 mmol/L; IGlar: 7.0 mmol/L). Hypoglycemia rates were lower for IDegAsp and IGlar than AF (1.2, 0.7, and 2.4 events/patient year). Nocturnal hypoglycemic events occurred rarely for IDegAsp (1 event) and IGlar (3 events) compared with AF (27 events).CONCLUSIONSIn this proof-of-concept trial, once-daily IDegAsp was safe, well tolerated, and provided comparable overall glycemic control to IGlar at similar low rates of hypoglycemia, but better postdinner plasma glucose control.

A Novel Insulin Combination of Insulin Degludec and Insulin Aspart Achieves a More Stable Overnight Glucose Profile Than Insulin Glargine: Results from Continuous Glucose Monitoring in a Proof-of-Concept Trial

“…8 Briefly, patients were included if they were insulin-naïve adults (18-75 years of age) with type 2 diabetes, had HbA1c of 7-11% and body mass index of 25-37 kg/m 2 , and were treated with up to two oral antidiabetic drugs (OADs; excluding thiazolidinediones) in the 2 months prior to trial at stable maximum doses or at least half maximum allowed doses. Fuller details on the inclusion and exclusion criteria have been reported previously.…”

“…Fuller details on the inclusion and exclusion criteria have been reported previously. 8 The patients were randomized in a 1:1:1 ratio to add a once-daily evening injection of IDegAsp, IGlar, or an alternative formulation of IDeg/IAsp. Except for metformin, all OADs were discontinued.…”

“…8 The two insulin treatments achieved equivalent hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) reductions, with low hypoglycemia rates. IDegAsp showed lower postdinner glucose excursions compared with IGlar, and the mean total insulin dose was lower with IDegAsp than with IGlar.…”

IDegAsp (insulin degludec + insulin aspart) for the management of type 2 diabetes: current status

“….0% vs. IGlar: 7.1%), but with better dinner-time postprandial glycemic control and lower rates of hypoglycemia [41]. The trend of lower hypoglycemia rates in phase 2 trials was later observed in phase 3 trials (Table 2).…”

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“…Due to its lesser day-to-day variability, degludec has the potential to further reduce the risk of hypoglycaemia than other long-acting basal insulins [9]. The DEVOTE study showed that degludec was non-inferior to glargine with respect to incidence of cardiovascular events with significant reductions in severe hypoglycaemia, especially nocturnal [10].…”