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

IntroductionTo 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.MethodsThis 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.ResultsThe 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]).ConclusionIDeg 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 RegistrationClinicaltrials.gov NCT01849289.Electronic supplementary materialThe online version of this article (doi:10.1007/s40268-016-0134-z) contains supplementary material, which is available to authorized users.

The Diabetes Unmet Need with Basal Insulin Evaluation (DUNE) study in type 2 diabetes: Achieving HbA1c targets with basal insulin in a real‐world setting

“…This may be related, in part, to insufficient insulin dose titration during the 12 weeks of treatment, as indicated by the 9 U and 5 U dose increases reported in the newly or previously initiated groups, respectively; such absence of intensive titration (titration inertia) has been reported previously in real-world clinical practice. [27][28][29] Importantly, mean daily insulin doses at the end of these treat-to-target studies reached between approximately 40 and 100 U/d, [27][28][29] considerably higher than those reached in this study. 26 Overall, however, no major difference in individualized HbA1c target achievement was observed between participantdriven or physician-driven titration, in either newly or previously initiated participants.…”

Comparative effectiveness and harms of long‐acting insulins for type 1 and type 2 diabetes: A systematic review and meta‐analysis

“…More evidence was available comparing degludec and glargine in patients with type 2 diabetes, with 10 good or fair‐quality trials in a total of >13 000 adult patients treated for 16 weeks to 2 years . An additional trial in 44 patients was rated poor quality .…”

“…Nine trials provided high‐strength evidence that glycaemic control did not differ between patients treated with degludec and glargine . About the same proportion of patients in both groups achieved HbA1c ≤7% in seven trials with 4716 participants (48% vs. 47%, pooled relative risk [RR] 0.97, 95% CI 0.91‐1.03; I 2 = 0%; see Appendix S1, Appendix F, Figure F‐1) . The DEVOTE and SWITCH2 trials together included more than 8000 patients, and neither trial found a statistically significant difference in mean HbA1c at the end of treatment with degludec compared with glargine.…”

“…Moderate strength evidence from nine trials in patients with type 2 diabetes showed lower rates of severe hypoglycaemia in patients given degludec than in those treated with glargine (3.3% vs. 5.1%, pooled RR 0.72, 95% CI 0.54‐0.96; I 2 = 12.5%; see Appendix S1, Appendix F, Figures F‐2 and F‐3). Rates of nocturnal hypoglycaemia were also lower; there were fewer episodes per patient‐year in patients given degludec than in those receiving glargine (eight randomized controlled studies, pooled RR 0.73, 95% CI 0.65‐0.82; I 2 = 0%; Figure ).…”

Management of Adults With Diabetes and Cognitive Problems

“…It is an ultra-long-acting insulin with daily dosing, but because of its long half-life, exact timing of the daily dose may not be as crucial. Initial studies have shown lower rates of hypoglycemia with insulin degludec compared to glargine and detemir (42,43). …”