A new-generation ultra-long-acting basal insulin with a bolus boost compared with insulin glargine in insulin-naive people with type 2 diabetes: a randomized, controlled trial

Tim Heise, Cees J Tack, Robert Cuddihy, Jaime Davidson, Didier Gouet, Andreas Liebl, Enrique Romero, Henriette Mersebach, Patrik Dykiel, Rolf Jorde, Tim Heise, Cees J Tack, Robert Cuddihy, Jaime Davidson, Didier Gouet, Andreas Liebl, Enrique Romero, Henriette Mersebach, Patrik Dykiel, Rolf Jorde

Abstract

Objective: Insulin 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 methods: In this 16-week, open-label trial, subjects (mean age 59.1 years, A1C 8.5%, BMI 30.3 kg/m(2)) 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.

Results: After 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).

Conclusions: In 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.

Trial registration: ClinicalTrials.gov NCT00614055.

Figures

Figure 1
Figure 1
Mean A1C over time (A), percentage of subjects achieving A1C targets of <7.0% and ≤6.5% at end of study (B), and percentage of subjects treated for at least 8 weeks achieving A1C targets of <7.0% and ≤6.5% at end of study in the absence of confirmed hypoglycemia (hypo.) in the last 4 weeks of treatment (C).
Figure 2
Figure 2
Mean 9-point SMPG profiles.

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