Efficacy and safety of insulin degludec/insulin aspart versus biphasic insulin aspart 30 in Chinese adults with type 2 diabetes: A phase III, open‐label, 2:1 randomized, treat‐to‐target trial

Abstract

Aims To assess the efficacy and safety of twice‐daily insulin degludec/insulin aspart (IDegAsp) versus biphasic insulin aspart 30 (BIAsp 30) twice daily, both ± metformin, in Chinese adults ( N = 543) with type 2 diabetes (T2D) inadequately controlled on premixed/self‐mixed or basal insulin ± metformin. Materials and methods We conducted a 26‐week, phase III, open‐label, treat‐to‐target, 2:1 randomized trial. Hierarchical testing was used with non‐inferiority of glycated haemoglobin (HbA1c) change from baseline to week 26 as the primary endpoint and superiority for the confirmatory secondary endpoints which were as follows: change from baseline in fasting plasma glucose (FPG); nocturnal confirmed hypoglycaemic episodes (12:01–5:59 am , inclusive); total confirmed hypoglycaemic episodes (severe or plasma glucose <3.1 mmol/L with/without symptoms); body weight; and percentage of responders (HbA1c <53 mmol/mol [<7.0%]) without confirmed hypoglycaemic episodes. Results Non‐inferiority for change from baseline to week 26 in HbA1c and superiority of IDegAsp twice daily versus BIAsp 30 twice daily for change in FPG, nocturnal confirmed and total confirmed hypoglycaemic episodes, was demonstrated. Estimated rates of nocturnal confirmed and total confirmed hypoglycaemic episodes were 47% and 43% lower, respectively, with IDegAsp twice daily versus BIAsp 30 twice daily. Superiority for change in body weight was not confirmed. Participants were more likely to reach the HbA1c goal of <53 mmol/mol (<7.0%) without confirmed hypoglycaemia with IDegAsp twice daily versus BIAsp 30 twice daily by trial end. No new safety signals were identified. Conclusions The efficacy and safety of IDegAsp in Chinese patients with T2D was demonstrated, confirming results from international trials.

Efficacy and Safety of Insulin Degludec/Insulin Aspart Compared with a Conventional Premixed Insulin or Basal Insulin: A Meta-Analysis

“…The literature search yielded 921 potentially relevant articles (PubMed 154, EMBASE 295, and Cochrane Library 472), of which 719 were screened for title and abstract after excluding 202 duplicate articles. Thereafter, 674 articles that did not meet the inclusion criteria were excluded, and the remaining 45 studies were evaluated for eligibility by performing a full-text review; finally, 17 studies [ 10 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ] with 3831 participants were included in this meta-analysis ( Figure 1 ). The effect on glycemic control and the risk of hypoglycemia development with those on the twice-daily IDegAsp regimen were reported in eight studies [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ], while those on the once-daily regimen were reported in nine studies [ 10 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ].…”

“…The demographic characteristics and main outcomes of each study are summarized in Table 1 . Of the 17 studies, 13 were randomized controlled trials (RCTs) and reported low risk of bias [ 10 , 15 , 16 , 17 , 19 , 20 , 22 , 24 , 25 , 26 , 27 , 28 ]. We classified one RCT with a serious risk of bias as we used the data to only determine the switch from once-daily basal insulin to once-daily IDegAsp [ 23 ].…”

Fear of hypoglycemia in adults with diabetes mellitus switching to treatment with IDegAsp co-formulation to examine real-world setting: an observational study (The HATICE study)

“…In a randomized controlled study conducted with the Chinese, IDegAsp was compared to BIAsp30. Superiority for change in weight and BMI was not confirmed according to phase III, open-label, treat-to-target trial of Yang et al [11]. In another treat-to-target trial conducted by Taneda et al, it has been observed that weight and BMI changes were similar after patients administering IDegAsp and administering BIasp30 for 26 weeks [13].…”

“…From this point of view, it can be considered as a summary of a multi-centered study. There are studies available demonstrating that IDe-gAsp treatment is safer compared to basal bolus and pre-mixed insulin regimes from the point of view of hypoglycemia [7,10,11]. In a phase 3 study in insulin-naïve Japanese adults, IDegAsp therapy was demonstrated to have at least as hypoglycemic safety as insulin glargine U100 [12].…”

Favorable Glycemic Control with Once-Daily Insulin Degludec/Insulin Aspart after Changing from Basal Insulin in Adults with Type 2 Diabetes

“…Additionally, it was expected that IDegAsp could theoretically regulate blood glucose with fewer hypoglycemic events than premixed biphasic insulin owing to the long duration of action and lower day-to-day variability of insulin degludec [9]. Consistent with this mechanism, it was reported that administrating IDegAsp twice a day controlled blood glucose levels more effectively than administrating premixed biphasic insulin, with fewer hypoglycemic events, in patients with type 2 diabetes [1011].…”