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


CONCLUSIONS
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.


BACKGROUND
Clinicaltrials.gov NCT01849289.
Department of Endocrinology, PLA General Hospital, No. 28 Fu Xing Road, Beijing, 100853, China. panchy301@126.com.
Changyu
C
Pan
Centro de Pesquisas em Diabetes, Porto Alegre, Brazil.
Jorge L
JL
Gross
Department of Endocrinology, China-Japan Friendship Hospital, Beijing, China.
Wenying
W
Yang
Department of Endocrinology, PLA Military General Hospital of Beijing, Beijing, China.
Xiaofeng
X
Lv
Siping Central People's Hospital, Siping, China.
Li
L
Sun
Novo Nordisk, Søborg, Denmark.
Charlotte Thim
CT
Hansen
Novo Nordisk China Pharmaceuticals, Beijing, China.
Hongfei
H
Xu
Community Research, Crestview Hills, KY, USA.
Robert
R
Wagner
D001786:Blood Glucose / Q000187:drug effects; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007003:Hypoglycemia / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D007328:Insulin; D000069036:Insulin Glargine / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D049528:Insulin, Long-Acting / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D016896:Treatment Outcome
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D008687:Metformin; C571886:insulin degludec