A Multinational, Randomized, Open-label, Treat-to-Target Trial Comparing Insulin Degludec and Insulin Glargine in Insulin-Naïve Patients with Type 2 Diabetes Mellitus

Abstract

Introduction: To lower the barrier for initiating insulin treatment and obtain adequate glycemic control in type 2 diabetes mellitus (T2DM), new basal insulin preparations with improved pharmacological properties and consequently a lower risk of hypoglycemia are needed. The objective of this trial was to confirm the efficacy and compare the safety of insulin degludec (IDeg) with insulin glargine (IGlar) in a multinational setting with two thirds of subjects enrolled in China.

Methods: This was a 26-week, randomized, open-label, parallel-group, treat-to-target, non-inferiority trial in 833 subjects with T2DM (48 % were female, mean age 56 years, diabetes duration 8 years), inadequately controlled on oral antidiabetic drugs (OADs). Subjects were randomized 2:1 to once-daily IDeg (555 subjects) or IGlar (278 subjects), both with metformin. The primary endpoint was the change from baseline in glycosylated hemoglobin (HbA1c) after 26 weeks.

Results: The completion rate was high (IDeg 94.2 %; IGlar 91.4 %). Mean HbA1c decreased from 8.3 to 7.0 % in both groups. Estimated treatment difference (ETD) [95 % confidence interval (CI)] IDeg-IGlar in change from baseline was -0.05 % points [-0.18 to 0.08], confirming the non-inferiority of IDeg to IGlar. The proportion of subjects achieving HbA1c <7.0 % was 54.2 and 51.4 % with IDeg and IGlar, respectively (estimated odds ratio [95 % CI] IDeg/IGlar: 1.14 [0.84 to 1.54]). The mean decrease in fasting plasma glucose, self-measured plasma glucose profiles, and insulin dose were similar between groups. Numerically lower rates of overall (estimated rate ratio [95 % CI] IDeg/IGlar: 0.80 [0.59 to 1.10]) and nocturnal (0.77 [0.43 to 1.37]) confirmed hypoglycemia were observed with IDeg compared with IGlar. No treatment differences in other safety parameters were found. Subjects were more satisfied with the IDeg device compared with the IGlar device as reflected by the total Treatment Related Impact Measures-Diabetes Device score (ETD [95 % CI] IDeg-IGlar: 2.2 [0.2 to 4.3]).

Conclusion: IDeg provided adequate glycemic control non-inferior to IGlar and a tendency for a lower hypoglycemia rate. IDeg is considered suitable for initiating insulin therapy in T2DM patients on OADs requiring intensified treatment.

Trial registration: Clinicaltrials.gov NCT01849289.

Figures

Fig. 1

Trial flow diagram. The full analysis set included all randomized subjects. The safety analysis set included all randomized subjects who received at least one dose of trial product. Most subjects withdrawn for “other” reasons were randomized in error (5 in the IDeg group, 3 in the IGlar group). % proportion of randomized subjects

Fig. 2

Glycemic control (full analysis set). a Mean HbA1c across the 26-week treatment period, b mean FPG across the 26-week treatment period, c 9-point SMPG profiles at baseline (week 0) and end of treatment (week 26). Glucose measurements for 9-point profiles were performed just before a meal and 90 minutes after start of the meal. Data are mean ± SEM. Missing data after baseline are imputed with the last observation carried forward method. IDeg insulin degludec, IGlar insulin glargine, HbA1c glycosylated hemoglobin, FPG fasting plasma glucose, SMPG self-measured plasma glucose, +90 min 90 min after start of the preceding meal, SEM standard error of the mean

Fig. 3

Cumulative number of confirmed hypoglycemic episodes across the 26-week treatment period (safety analysis set). a Overall confirmed hypoglycemic episodes. b Nocturnal confirmed hypoglycemic episodes. Confirmed hypoglycemic episodes included episodes of severe hypoglycemia as well as hypoglycemic episodes with confirmed plasma glucose <3.1 mmol/L. Nocturnal hypoglycemic episodes were defined as episodes with time of onset between 00:01 and 05:59 (both inclusive). IDeg insulin degludec, IGlar insulin glargine