Effectiveness of insulin degludec/liraglutide versus insulin degludec/insulin aspart in Japanese patients with type 2 diabetes.

Aims: To evaluate and compare the effectiveness of once-daily insulin degludec/liraglutide (IDegLira) to that of once-daily insulin degludec/insulin aspart (IDegAsp) after switching from basal insulin therapy at 6 months by assessing changes in hemoglobin A1c (HbA1c), body weight, and insulin doses in patients with type 2 diabetes (T2D). Materials and methods: A total of 91 patients with T2D with HbA1c levels exceeding 7.0% were included in this study. Adjusted least square mean changes in HbA1c, body weight, and total insulin doses were compared between the IDegLira group and IDegAsp group. Subgroup analyses were performed, stratified by median values of HbA1c (< 8.5 and ≥ 8.5%), obesity (body mass index < 25 and ≥ 25 kg/m2), and basal insulin doses (< 14 and ≥ 14 units) at baseline to assess treatment interaction by subgroup. Results: The IDegLira group showed a greater reduction in HbA1c levels than the IDegAsp group (- 0.17 vs - 0.79%, p = 0.003) with comparable body weight changes. The analyses of adjusted mean changes of total insulin doses showed that the IDegAsp group had a larger increase than the IDegLira group (3.64 vs 1.30 unis, p = 0.016). The effect of IDegLira on HbA1c levels was superior to that of IDegAsp in patients with high HbA1c. There were no inter-group differences in the rate of hypoglycemic episodes. Conclusions: Once-daily IDegLira had greater effects on HbA1c and a lesser increase in insulin doses than IDegAsp when patients are switched from basal insulin therapy. Moreover, the effect on HbA1c was enhanced in patients with high HbA1c levels at baseline.

Efficacy and Safety of IDegAsp in a Real-World Korean Population with Type 2 Diabetes Mellitus.

Background: This study investigated the real-world efficacy and safety of insulin degludec/insulin aspart (IDegAsp) in Korean adults with type 2 diabetes mellitus (T2DM), whose insulin treatment was switched to IDegAsp. Methods: This was a multicenter, retrospective, observational study comprising two 26-week treatment periods, before and after switching to IDegAsp, respectively. Korean adults with uncontrolled T2DM treated with basal or premix insulin (±oral antidiabetic drugs) were enrolled. The primary objective was to compare the degree of glycosylated hemoglobin (HbA1c) change in each 26-week observation period. The analyses included changes in HbA1c, fasting plasma glucose (FPG), body weight, proportion of participants achieving HbA1c <7.0%, hypoglycemic events, and total daily insulin dose (ClinicalTrials.gov, number NCT04656106). Results: In total, 196 adults (mean age, 65.95 years; mean T2DM duration, 18.99 years) were analyzed. The change in both HbA1c and FPG were significantly different between the pre-switching and the post-switching period (0.28% vs. -0.51%, P<0.001; 5.21 mg/dL vs. -23.10 mg/dL, P=0.005), respectively. After switching, the rate of achieving HbA1c <7.0% was significantly improved (5.10% at baseline vs. 11.22% with IDegAsp, P=0.012). No significant differences (before vs. after switching) were observed in body weight change, and total daily insulin dose. The rates of overall and severe hypoglycemia were similar in the two periods. Conclusion: In real-world clinical practice in Korea, the change of insulin regimen to IDegAsp was associated with an improvement in glycemic control without increase of hypoglycemia, supporting the use of IDegAsp for patients with T2DM uncontrolled with basal or premix insulin.

Comparative efficacy and safety of Gla-300 versus IDegAsp in insulin-naïve people with type 2 diabetes mellitus uncontrolled on oral anti-diabetics.

AIM: To compare the efficacy and safety of insulin glargine-300 once daily (Gla-300) with insulin degludec/aspart (IDegAsp) once daily in patients with type 2 diabetes (T2D) inadequately controlled on oral anti-diabetic drugs (OADs). MATERIALS AND METHODS: A systematic literature review of randomized controlled trials was followed by an indirect treatment comparison of studies involving insulin naïve adults, inadequately controlled [glycated haemoglobin (HbA1c) ≥7.0%] on OADs, who received Gla-300 or IDegAsp once daily. Outcomes of interest were change in HbA1c, blood glucose, weight and insulin dose, as well as incidence and event rate of hypoglycaemia and other adverse events. RESULTS: Four trials with broadly similar baseline patient characteristics were included in the meta-analyses and indirect treatment comparison. At 24-28 weeks, the indirect comparison of Gla-300 to IDegAsp once daily estimated no statistically significant difference for change in HbA1c (%) from baseline [mean difference of 0.10% (95% CI: -0.20, 0.39; p = .52)]; a statistically significant mean difference of -1.31 kg (95% CI: -1.97, -0.65; p < .05) for change in body weight from baseline; statistically significant odds ratios of 0.62 (95% CI: 0.41, 0.93; p < .05) for incidence of any hypoglycaemia; and 0.47 (95% CI: 0.25, 0.87; p < .05) for incidence of anytime confirmed hypoglycaemia (plasma glucose <3.0-3.1 mmol/L). No significant differences were observed for insulin dose and adverse events. CONCLUSION: In insulin-naïve patients with T2D inadequately controlled on OADs, commencing Gla-300 shows a comparable HbA1c reduction, but with significantly less weight gain and a lower incidence of any and confirmed hypoglycaemia compared with commencing IDegAsp.

Therapeutic effects of insulin degludec/insulin aspart on type 2 diabetes mellitus in patients with poor efficacy of oral hypoglycemic drugs / 中国基层医药

Objective:To investigate the clinical efficacy of insulin degludec/insulin aspart on type 2 diabetes mellitus in patients with poor efficacy of oral hypoglycemic drugs.Methods:A total of 100 patients with type 2 diabetes mellitus in Tianfu Hospital of Chongqing Energy Investment Health Industry Company Limited from August 2020 to August 2021 were included in this study. They were randomly assigned to receive either insulin degludec/insulin aspart combined with Metformin (observation group, n = 50) or nsulin aspart 30 injection and Metformin (control group, n = 50). All patients were treated for 3 months. Changes in fasting plasma glucose level, 2-hour postprandial glucose level , and HbAlc after treatment relative to those before treatment as well as clinical efficacy were determined in each group. Results:Forty-eight patients in the observation group and forty-six patients in the control group completed the course of treatment. Fasting blood glucose level and 2-hour postprandial glucose level in the observation group were (6.24 ± 1.12) mmol/L and (8.34 ± 2.34) mmol/L, respectively and they were significantly lower than (6.91 ± 1.86) mmol/L and (10.72 ± 2.48) mmol/L, respectively in the control group ( t = 3.28, 4.76, both P < 0.05). The level of HbAlc was not significant between the two groups ( P > 0.05). The hypoglycemia rate in the observation group was significantly lower than that in the control group [2% (1/48) vs. 13% (6/46), χ2 = 4.09, P < 0.05]. The daily dose of insulin in the observation group was less than that in the control group [(13.5 ± 2.8) IU vs. (15.6 ± 3.1) IU, t = 3.28, P < 0.05)]. Conclusion:Compared with insulin insulin aspart 30, the insulin degludec/insulin aspart has a stronger hypoglycemic effect on fasting plasma glucose level and 2-hour postprandial glucose level in the treatment of type 2 diabetes mellitus in patients with poor efficacy of oral hypoglycemic drugs, leading to a less daily dose of insulin.

Cost-effectiveness of insulin degludec/insulin aspart versus biphasic insulin aspart in Chinese population with type 2 diabetes.

Objective: To evaluate the long-term cost effectiveness of insulin degludec/insulin aspart (IDegAsp) vs. biphasic insulin aspart 30 (BIAsp 30) for the treatment of people with type 2 diabetes mellitus (T2DM) inadequately managed on basal insulin in China. Methods: The CORE (the Center for Outcomes Research) Diabetes Model, which has been published and verified, was used to simulate disease progression and calculate the total direct medical costs, life years (LYs) and quality-adjusted life years (QALYs) over 30 years, from the perspective of Chinese healthcare system. The patient demographic information and clinical data needed for the model were gathered from a phase III treat-to-target clinical trial (NCT02762578) and other Chinese cohort studies. Medical costs on treating diabetes were calculated based on clinical trial and local sources. The diabetes management and complications costs were derived from published literature. A discounting rate of 5% was applied to both health and cost outcomes. And one-way and probabilistic sensitivity analyses were carried out to test the reliability of the results. Results: Compared with BIAsp 30, treatment with IDegAsp was associated with an incremental benefit of 0.001 LYs (12.439 vs. 12.438) and 0.280 QALYs (9.522 vs. 9.242) over a 30-year time horizon, and increased CNY (Chinese Yuan) 3,888 (390,152 vs. 386,264) for total costs. IDegAsp was cost-effective vs. BIAsp 30 therapy with an incremental cost-effectiveness ratio of CNY 13,886 per QALY gained. Results were robust across a range of sensitivity analyses. Conclusion: Compared with BIAsp 30, IDegAsp was a cost-effective treatment option for people with T2DM with inadequate glycemic management on basal insulin in China.

Initiating or Switching to Insulin Degludec/Insulin Aspart in Adults with Type 2 Diabetes: A Real-World, Prospective, Non-interventional Study Across Six Countries.

INTRODUCTION: Insulin degludec/insulin aspart (IDegAsp) is a fixed-ratio co-formulation of insulin degludec (a basal insulin) and insulin aspart (a prandial insulin). The aim of this study was to investigate clinical outcomes in people with type 2 diabetes (T2D) after initiating IDegAsp treatment in a real-world setting. METHODS: This 26-week, open-label, non-interventional study was conducted in Australia, India, Malaysia, Philippines, Saudi Arabia, and South Africa. Data were obtained from 1102 adults with T2D initiating or switching to IDegAsp from antidiabetic treatments (including oral antidiabetic drugs, basal insulin, basal-bolus insulin, premix insulin, and glucagon-like peptide 1 receptor agonist) per local clinical practice. RESULTS: Compared with baseline, there was significant improvement in HbA1c at end of study (EOS, first visit within weeks 26-36; estimated change - 1.4% [95% CI - 1.51; - 1.29]; P < 0.0001 [primary outcome]). From baseline to EOS, there were significant reductions in fasting plasma glucose (- 2.7 mmol/L [95% CI - 2.98; - 2.46]; P < 0.0001), body weight (- 1.0 kg [95% CI - 1.51; - 0.52]; P < 0.0001), and basal insulin dose in insulin-experienced participants (- 2.3 units [95% CI - 3.51; - 1.01]; P < 0.001). The incidence rates of non-severe (overall and nocturnal) and severe hypoglycaemia decreased significantly (P < 0.001) between the period before baseline and before EOS. CONCLUSION: In adults with T2D, initiating or switching to IDegAsp from previous antidiabetic treatment was associated with improved glycaemic control, lower basal insulin dose (in insulin-experienced participants), and lower rates of hypoglycaemia. TRIAL REGISTRATION: Clinical trial registration NCT04042441.

Low fasting glucose-to-estimated average glucose ratio was associated with superior response to insulin degludec/aspart compared with basal insulin in patients with type 2 diabetes.

AIMS/INTRODUCTION: The benefits of once-daily insulin degludec/aspart (IDegAsp) compared with basal insulin in type 2 diabetes patients have not been established. MATERIALS AND METHODS: This was a retrospective observational study. From a basal insulin cohort from three referral hospitals, patients were enrolled who initiated once-daily IDegAsp. A control group maintaining basal insulin was selected by propensity score matching. Glycated hemoglobin (HbA1c) changes over a period of 6 months and associated clinical factors were evaluated. RESULTS: The IDegAsp group and the control group comprised of 87 patients, respectively. Baseline HbA1c was comparable between the two groups (8.7 ± 0.9 vs 8.6 ± 0.9%, mean and standard deviation). After 6 months with matched insulin doses, HbA1c in the IDegAsp group was lower than that in the control group (8.1 ± 1.0 vs 8.4 ± 1.1%, P = 0.029). Among baseline variables, fasting plasma glucose (FPG) and fasting C-peptide in the IDegAsp were lower than that in the control (FPG 124.2 ± 38.4 vs 148.0 ± 50.6 mg/dL, P < 0.001). Considering that the lower FPG despite the comparable HbA1c could be related with the efficacy of IDegAsp, subgroup analysis was carried out according to a ratio of FPG-to-estimated average glucose, which is calculated from HbA1c. When compared with each control group, the superiority of IDegAsp in the reduction of HbA1c was significant only in the patients with a lower FPG-to-estimated average glucose ratio (0.49 ± 0.09), but not in those with a higher FPG-to-estimated average glucose ratio (0.79 ± 0.20). CONCLUSIONS: We observed that IDegAsp was more effective than basal insulin in patients with an FPG lower than predicted by HbA1c, which might be related with insulin deficiency and postprandial hyperglycemia in patients on basal insulin therapy.

A Real-World, Prospective, Non-interventional Study of Adults with T2D Switching to IDegAsp from Glargine U100 or U300 in Japan.

INTRODUCTION: This real-world study investigated glycaemic control and quality of life (QoL) in insulin-experienced Japanese patients with type 2 diabetes (T2D) who switched to insulin degludec/insulin aspart (IDegAsp). METHODS: This was a prospective, non-interventional, open-label, single-arm study. Eligible patients were adults (aged ≥ 20 years) with T2D, previously treated with insulin glargine 100 or 300 units/mL (glargine U100/U300) with or without prandial insulin, who switched to IDegAsp as part of routine practice. Change from baseline to end of study (EOS; 26 weeks after initiation or IDegAsp discontinuation) in the following endpoints was assessed by adjusted mixed models for repeated measures: glycated haemoglobin (HbA1c; primary endpoint), fasting plasma glucose (FPG), insulin dose and total Diabetes Therapy-Related Quality of Life (DTR-QoL) score. Non-severe hypoglycaemia was assessed in the 4-week period prior to initiating IDegAsp and in the 4-week period before EOS or discontinuation using negative binomial regression. RESULTS: The full analysis set included 236 patients from 29 centres in Japan with mean (± SD) age 63.2 years (± 12.3), HbA1c 7.7% (± 1.0) and diabetes duration 14.9 (± 9.3) years. After 26 weeks with IDegAsp, HbA1c (estimated change - 0.1% [- 0.2; 0.0]95% confidence interval (CI), p = 0.3036) and FPG (- 7.5 mg/dL [- 23.5; 8.5]95% CI, p = 0.3477) were maintained; there were significant reductions in basal and total insulin dose: estimated change of - 3.4 units/day [- 3.8; - 3.0]95% CI and - 1.0 units/day [- 1.9; - 0.1]95% CI, respectively (both p < 0.05). Non-severe hypoglycaemia rates were similar in the periods before and after initiating IDegAsp, while there was a significant improvement in total DTR-QoL score after 26 weeks with IDegAsp (p = 0.0012). CONCLUSION: These real-world data suggest that switching to IDegAsp from glargine U100 or U300 was well tolerated in a Japanese population with T2D, with no new safety or tolerability signals, and associated with maintenance of glycaemic control and improved QoL. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov: NCT03745157.

The Clinical Role of Insulin Degludec/Insulin Aspart in Type 2 Diabetes: An Empirical Perspective from Experience in Australia.

Treatment intensification in people with type 2 diabetes following failure of basal insulin commonly involves the addition of a rapid-acting insulin analogue (basal plus one or more prandial doses; multiple daily injections) or by a switch to premixed insulin. Insulin degludec/insulin aspart (IDegAsp), comprising rapid-acting insulin aspart and ultra-long-acting insulin degludec in solution, enables both fasting and post-prandial glucose control, with some advantages over other treatment intensification options. These include straightforward dose titration, flexibility in dose timing, low injection burden, simplicity of switching and a lower risk of hypoglycaemia. In Australia, where insulin degludec on its own is not available, IDegAsp enables patients to still benefit from its ultra-long-acting properties. This review aims to provide guidance on where and how to use IDegAsp. Specifically, guidance is included on the initiation of IDegAsp in insulin-naïve patients, treatment intensification from basal insulin, switching from premixed or basal-bolus insulin to IDegAsp, up-titration from once- to twice-daily IDegAsp and the use of IDegAsp in special populations or situations.

Switching to Once-Daily Insulin Degludec/Insulin Aspart from Basal Insulin Improves Postprandial Glycemia in Patients with Type 2 Diabetes Mellitus: Randomized Controlled Trial.

BACKGROUND: To explore the efficacy and safety of switching from once-daily basal insulin therapy to once-daily pre-meal injection insulin degludec/insulin aspart (IDegAsp) with respect to the glycemic control of participants with type 2 diabetes mellitus (T2DM). METHODS: In this multicenter, open-label, prospective, randomized, parallel-group comparison trial, participants on basal insulin therapy were switched to IDegAsp (IDegAsp group; n=30) or continued basal insulin (Basal group; n=29). The primary endpoint was the superiority of IDegAsp in causing changes in the daily blood glucose profile, especially post-prandial blood glucose concentration after 12 weeks. RESULTS: Blood glucose concentrations after dinner and before bedtime were lower in the IDegAsp group, and the improvement in blood glucose before bedtime was significantly greater in the IDegAsp group than in the Basal group at 12 weeks (-1.7±3.0 mmol/L vs. 0.3±2.1 mmol/L, P<0.05). Intriguingly, glycemic control after breakfast was not improved by IDegAsp injection before breakfast, in contrast to the favorable effect of injection before dinner on blood glucose after dinner. Glycosylated hemoglobin significantly decreased only in the IDegAsp group (58 to 55 mmol/mol, P<0.05). Changes in daily insulin dose, body mass, and recorded adverse effects, including hypoglycemia, were comparable between groups. CONCLUSION: IDegAsp was more effective than basal insulin at reducing blood glucose after dinner and before bedtime, but did not increase the incidence of hypoglycemia. Switching from basal insulin to IDegAsp does not increase the burden on the patient and positively impacts glycemic control in patients with T2DM.

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

BACKGROUND: Conflicting results have been reported on the efficacy of insulin degludec/insulin aspart (IDegAsp) compared to basal insulin in type 2 diabetes. We investigated the effects of changing basal insulin to IDegAsp on glycemic control and sought to identify factors related to those effects. METHODS: In this retrospective study of patients from three referral hospitals, patients with type 2 diabetes using basal insulin with hemoglobin A1c (HbA1c) levels less than 11.0% were enrolled. Basal insulin was replaced with IDegAsp, and data were analyzed from 3 months before to 3 months after the replacement. RESULTS: Eighty patients were recruited (52.5% male; mean age, 67.0±9.8 years; mean duration of diabetes, 18.9±8.5 years; mean HbA1c, 8.7%±1.0%). HbA1c levels increased during 3 months of basal insulin use, but significantly decreased after changing to IDegAsp (8.28%±1.10%, P=0.0001). The reduction was significant at 6 months in 35 patients whose longer-term data were available. Patients with a measured fasting plasma glucose (m-FPG) lower than their predicted FPG (p-FPG) by regression from HbA1c showed a significant HbA1c reduction caused by the change to IDegAsp, even without a significantly increased insulin dose. However, patients whose m-FPG was higher than their p-FPG did not experience a significant HbA1c reduction, despite a significantly increased insulin dose. Furthermore, the HbA1c reduction caused by IDegAsp was significant in patients with low fasting C-peptide levels and high insulin doses. CONCLUSION: We observed a significant glucose-lowering effect by replacing basal insulin with IDegAsp, especially in patients with a lower m-FPG than p-FPG.

Comparison of the efficacy and safety of once-daily insulin degludec/insulin aspart (IDegAsp) and long-acting second-generation basal insulin (insulin degludec and insulin glargine 300 units/mL) in insulin-naïve Japanese adults with type 2 diabetes: a pilot, randomized, controlled study.

To examine the efficacy and safety of once-daily insulin degludec/insulin aspart (IDegAsp) or once-daily second-generation basal insulin analogs (insulin degludec and insulin glargine 300 units/mL) in insulin-naïve Japanese adults with type 2 diabetes in routine clinical practice. A 12-week multicenter, open-label, randomized, pilot study was performed in 52 subjects with type 2 diabetes treated with oral antidiabetic drugs (OADs). Subjects were randomized to once-daily IDegAsp (n = 26) or basal insulin (n = 26). The primary endpoint was percent change in HbA1c from baseline to week 12. Furthermore, it was analyzed post hoc in subgroups stratified by baseline HbA1c. During a follow-up period, percent change in HbA1c was not significantly different between the two groups (p = 0.161). Daily insulin doses and frequency of overall hypoglycemia were also similar in the two groups. In post hoc analyses, once-daily basal insulin was more effective than IDegAsp in subjects with HbA1c more than or equal to 8.5% (p < 0.05); however, in subjects with HbA1c less than 8.5%, once-daily IDegAsp showed a significant improvement in percent change in HbA1c at week 12, compared with basal insulin (p < 0.01). Although there was no apparent difference in the HbA1c-lowering effects between two groups, when compared in subjects with HbA1c less than 8.5%, once-daily IDegAsp showed a significant effect in comparison with once-daily basal insulin. These findings suggest that the baseline HbA1c level might provide the important information for choosing IDegAsp or basal insulin in patients insufficiently controlled with OADs. This trial was registered with UMIN (no. UMIN000035431).

The rate of hyperglycemia and ketosis with insulin degludec-based treatment compared with insulin detemir in pediatric patients with type 1 diabetes: An analysis of data from two randomized trials.

BACKGROUND: Historically, data on the rate of hyperglycemia and ketosis have not been collected in clinical trials. However, it is clinically important to assess the rate of these events in children with type 1 diabetes (T1D). This question was addressed in two pediatric trials using insulin degludec (degludec). OBJECTIVE: To assess the rate of hyperglycemia and ketosis in two-phase 3b trials investigating degludec (Study 1) and degludec with insulin aspart (IDegAsp [Study 2]) vs insulin detemir (IDet). SUBJECTS: Patients (aged 1-17 years inclusive) with T1D treated with insulin for ≥3 months. METHODS: Study 1: patients were randomized to degludec once daily (OD) or IDet OD/twice daily (BID) for 26 weeks, followed by a 26-week extension phase. Study 2: patients were randomized to IDegAsp OD or IDet OD/BID for 16 weeks. Bolus mealtime IAsp was included in both studies. In Study 1, hyperglycemia was recorded if plasma glucose (PG) was >11.1 mmol/L, with ketone measurement required with significant hyperglycemia (>14.0 mmol/L). In Study 2, hyperglycemia was recorded with PG >14.0 mmol/L where the subject looked/felt ill, with ketone measurement also required in these hyperglycemic patients. In this post hoc analysis, the hyperglycemia threshold was 14.0 mmol/L for uniformity. RESULTS: Despite similar rates of hyperglycemia with degludec/IDegAsp compared with IDet, the rates of ketosis were lower with degludec/IDegAsp. CONCLUSIONS: These trials, the first to systematically collect data on ketosis in pediatric patients with T1D, demonstrate the potential of degludec/IDegAsp to reduce rates of metabolic decompensation, compared with IDet.

Efficacy and Safety of IDegAsp Versus BIAsp 30, Both Twice Daily, in Elderly Patients with Type 2 Diabetes: Post Hoc Analysis of Two Phase 3 Randomized Controlled BOOST Trials.

INTRODUCTION: The majority of elderly patients (≥ 65 years of age) with type 2 diabetes mellitus (T2DM) will eventually require insulin therapy, but they are particularly vulnerable to hypoglycemia and challenging to treat. Insulin degludec/insulin aspart (IDegAsp) is a novel co-formulation of 70% insulin degludec and 30% insulin aspart administered in a single injection, either once or twice daily with main meals. METHODS: A combined analysis of the phase 3 BOOST INTENSIFY PREMIX I (NCT01009580) and BOOST INTENSIFY ALL (NCT01059812) trials has previously reported lower rates of hypoglycemia during the maintenance period in patients with T2DM treated with IDegAsp twice daily (BID) versus biphasic insulin aspart 30 (BIAsp 30) BID. This post hoc analysis examined the safety and efficacy of IDegAsp versus BIAsp 30 in elderly patients from the global population of these two trials, and also from the Japanese cohort of BOOST INTENSIFY ALL. RESULTS: Change in HbA1c was similar for IDegAsp versus BIAsp 30 (p > 0.5). Compared with BIAsp 30, IDegAsp resulted in significant reductions in fasting plasma glucose (p < 0.0001), numerically lower rates of overall and nocturnal hypoglycemia (global estimated rate ratios: 0.92 [0.67; 1.26]95% confidence interval [CI], p = 0.5980 and 0.67 [0.39; 1.18]95% CI, p = 0.1676, respectively), and a significantly lower total daily insulin dose at end of trial (global estimated treatment difference 0.79 [0.73; 0.87]95% CI, p < 0.0001) in elderly patients. CONCLUSION: The results described here are consistent with those of the overall trial populations, demonstrating that IDegAsp BID is efficacious in elderly patients and suggesting that there is no need for special safety precautions. FUNDING: Novo Nordisk. TRIAL REGISTRATION: ClinicalTrials.gov identifiers, NCT01009580 and NCT01059812. Plain language summary available for this article.

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

BACKGROUND: Conflicting results have been reported on the efficacy of insulin degludec/insulin aspart (IDegAsp) compared to basal insulin in type 2 diabetes. We investigated the effects of changing basal insulin to IDegAsp on glycemic control and sought to identify factors related to those effects.METHODS: In this retrospective study of patients from three referral hospitals, patients with type 2 diabetes using basal insulin with hemoglobin A1c (HbA1c) levels less than 11.0% were enrolled. Basal insulin was replaced with IDegAsp, and data were analyzed from 3 months before to 3 months after the replacement.RESULTS: Eighty patients were recruited (52.5% male; mean age, 67.0±9.8 years; mean duration of diabetes, 18.9±8.5 years; mean HbA1c, 8.7%±1.0%). HbA1c levels increased during 3 months of basal insulin use, but significantly decreased after changing to IDegAsp (8.28%±1.10%, P=0.0001). The reduction was significant at 6 months in 35 patients whose longer-term data were available. Patients with a measured fasting plasma glucose (m-FPG) lower than their predicted FPG (p-FPG) by regression from HbA1c showed a significant HbA1c reduction caused by the change to IDegAsp, even without a significantly increased insulin dose. However, patients whose m-FPG was higher than their p-FPG did not experience a significant HbA1c reduction, despite a significantly increased insulin dose. Furthermore, the HbA1c reduction caused by IDegAsp was significant in patients with low fasting C-peptide levels and high insulin doses.CONCLUSION: We observed a significant glucose-lowering effect by replacing basal insulin with IDegAsp, especially in patients with a lower m-FPG than p-FPG.

Twice-daily insulin degludec/insulin aspart effectively improved morning and evening glucose levels and quality of life in patients previously treated with premixed insulin: an observational study.

BACKGROUND: Previous studies comparing insulin degludec/insulin aspart (IDegAsp) with premixed insulin twice daily among insulin users with type 2 diabetes have not thoroughly investigated differences in the glucose variability and psychological evaluations related to insulin regimen changes. We investigated changes in the daily and day-to-day glucose variability and quality of life (QOL) related to insulin use in patients with type 2 diabetes during a switch from premixed insulin preparations comprising either human insulin (BHI30) or insulin aspart (BIAsp30) to IDegAsp twice daily. METHODS: In this prospective observational study, 22 subjects (BHI30:BIAsp30 = 12:10) self-measured their blood glucose levels every morning, and before and after all meals each week. Premixed insulin was administered for the first 2 months, followed by IDegAsp for the next 2 months. Efficacy measures were evaluated during the last month or last day of both phases. RESULTS: The mean blood glucose levels (175.5 vs. 163.0 mg/dL; P = 0.004) and the M-values (53.9 vs. 27.6; P = 0.049) were significantly lower in the IDegAsp phase. However, no differences in the standard deviations of morning fasting glucose levels were observed between phases (premixed vs. IDegAsp, 20.0 vs. 19.3 mg/dL; P = 0.343). Compared to the premixed phase, the before-breakfast (145.3 vs. 126.0 mg/dL; P < 0.001), after-breakfast (190.3 vs. 170.7 mg/dL; P = 0.001), before-dinner (153.0 vs. 140.1 mg/dL; P  = 0.007), and after-dinner glucose levels (198.7 vs. 181.4 mg/dL; P = 0.018) were lower in the IDegAsp phase. However, the before-lunch (150.8 vs. 148.2 mg/dL; P  = 0.329) and after-lunch glucose levels (214.7 vs. 211.4 mg/dL; P = 0.308) did not significantly differ between phases. Regarding QOL, the total and therapy-related feeling Insulin Therapy Related-QOL (ITR-QOL) questionnaire scores favored IDegAsp, as did the ITR-QOL at Night questionnaire subscale score of glycemic control before breakfast. CONCLUSIONS: Although the day-to-day variability of morning fasting glucose levels did not change, switching to IDegAsp improved daily glucose level variability, the morning and evening glucose control and QOL among patients treated with premixed insulin.Trial registration University Hospital Medical Information Network Clinical Trials Registry, UMIN000021939. Prospectively registered 18 April 2016.

Efficacy and safety of a fixed combination of insulin degludec/insulin aspart in children and adolescents with type 1 diabetes: A randomized trial.

BACKGROUND: Insulin degludec/insulin aspart (IDegAsp) is a fixed soluble co-formulation of basal and bolus insulin. OBJECTIVE: To evaluate efficacy and safety of IDegAsp in pediatric patients with type 1 diabetes (T1D). SUBJECTS: Children and adolescents (aged 1 to <18 years) with T1D. METHODS: A 16-week, phase 3b, treat-to-target, parallel-group, open-label, non-inferiority trial was conducted at 63 sites in 14 countries from October 2013 to November 2014. Patients were randomized 1:1 (age stratified: 1-<6 years; 6-<12 years; 12-<18 years) to IDegAsp once daily (OD) plus insulin aspart (IAsp) for remaining meals (IDegAsp + IAsp), or IDet OD or twice daily plus mealtime IAsp (IDet + IAsp). The primary end-point was HbA1c change from baseline at week 16. RESULTS: A total of 362 participants were randomized to IDegAsp + IAsp (n = 182) or IDet + IAsp (n = 180). HbA1c decreased from baseline to week 16 by 0.3% in both groups (estimated treatment difference: -0.04%-points [-0.23; 0.15]95%CI (-0.45 mmol/mol [-2.51; 1.60]95%CI ), confirming non-inferiority. There were no significant differences between treatment groups in fasting or self-measured plasma glucose. Confirmed hypoglycemia rates did not significantly differ between groups. There was a significant reduction in basal and total insulin dose with IDegAsp + IAsp vs IDet + IAsp (post hoc analysis). Mean number of injections/day was 3.6 and 4.9 with IDegAsp + IAsp and IDet + IAsp, respectively (post hoc analysis). A non-significant higher rate of severe hypoglycemia was observed with IDegAsp + IAsp vs IDet + IAsp. The most frequent adverse events in both groups were hypoglycemia, headache, and nasopharyngitis. CONCLUSIONS: IDegAsp + IAsp was non-inferior to IDet + IAsp regarding HbA1c, had similar hypoglycemia rates and required fewer injections.

Finally, after 56 years of type 1 diabetes: a regimen that works.

Prior to the availability of degludec and regular human insulin inhalation powder in the type 1 diabetic patient glycemic control with subcutaneous insulin injections was difficult to obtain due to nocturnal, pre-prandial and often severe hypoglycemia as well as post-prandial hyperglycemia and hypoglycemia due to 'stacking' of insulin. A 62-year-old female with type 1 diabetes for 56 years who could not be controlled with continuous subcutaneous insulin aspart infusion obtained glycemic control without significant hypoglycemia or increased post-prandial glycemic excursions utilizing degludec insulin for basal needs and technosphere before meals and between meals if needed. The availability of degludec and technosphere insulin improved the management of brittle type 1 diabetes.

Original paper: Efficacy and safety analysis of insulin degludec/insulin aspart compared with biphasic insulin aspart 30: A phase 3, multicentre, international, open-label, randomised, treat-to-target trial in patients with type 2 diabetes fasting during Ramadan.

AIMS: To compare the efficacy and safety of insulin degludec/insulin aspart (IDegAsp) and biphasic insulin aspart 30 (BIAsp 30) before, during and after Ramadan in patients with type 2 diabetes mellitus (T2DM) who fasted during Ramadan. METHODS: In this multinational, randomised, treat-to-target trial, patients with T2DM who intended to fast and were on basal, pre- or self-mixed insulin ±â€¯oral antidiabetic drugs for ≥90 days were randomised (1:1) to IDegAsp twice daily (BID) or BIAsp 30 BID. Treatment period included pre-Ramadan treatment initiation (with insulin titration for 8-20 weeks), Ramadan (4 weeks) and post-Ramadan (4 weeks). Insulin doses were reduced by 30-50% for the pre-dawn meal (suhur) on the first day of Ramadan, and readjusted to the pre-Ramadan levels at the end of Ramadan. Hypoglycaemia was analysed as overall (severe or plasma glucose <3.1 mmol/L [56 mg/dL]), nocturnal (00:01-05:59) or severe (requiring assistance of another person). RESULTS: During the treatment period, IDegAsp (n = 131) had significantly lower overall and nocturnal hypoglycaemia rates with similar glycaemic efficacy, versus BIAsp 30 (n = 132). During Ramadan, despite achieving significantly lower pre-iftar (meal at sunset) self-measured plasma glucose (estimated treatment difference: -0.54 mmol/L [-1.02; -0.07]95% CI, p = .0247; post hoc) with similar overall glycaemic efficacy, IDegAsp showed significantly lower overall and nocturnal hypoglycaemia rates versus BIAsp 30. CONCLUSIONS: IDegAsp is a suitable therapeutic agent for patients who need insulin for sustained glucose control before, during and after Ramadan fasting, with a significantly lower risk of hypoglycaemia, versus BIAsp 30, an existing premixed insulin analogue.

Efficacy and safety of switching from basal insulin to once-daily insulin degludec/insulin aspart in Japanese patients with inadequately controlled type 2 diabetes: A 4-week, randomized, open-label, treat-to-target study.

AIMS/INTRODUCTION: A prospective, 4-week, single-center, randomized, open-label, parallel-group, treat-to-target study was carried out to develop an algorithm for safe and effective switching from basal insulin to once-daily insulin degludec/insulin aspart (IDegAsp) in patients with inadequately controlled type 2 diabetes. MATERIALS AND METHODS: Patients were randomly assigned to continue their current basal insulin therapy (n = 10) or to switch to IDegAsp on a 1:1 unit basis (n = 10). The insulin dose could be titrated once weekly, targeting a self-measured blood glucose of 80-100 mg/dL before breakfast. A mixed meal test was carried out at baseline and after 4 weeks. RESULTS: After 4 weeks, the mean daily dose of insulin was similarly increased by 60% in both groups, and there was a significant decrease of mean plasma glucose and glucose area under the glucose concentration vs time curve for 2 h in the meal test. The mean estimated treatment difference (IDegAsp group - basal insulin group) of the mean plasma glucose level was -28 mg/dL (95% confidence interval -47 to -8, P = 0.008) after 4 weeks and that of the area under the glucose concentration vs time curve for 2 h was -2,800 mg/min/dL (95% confidence interval -5,300 to -350, P = 0.028), confirming the superiority of IDegAsp to basal insulin. In the IDegAsp group, the 2-h postprandial plasma glucose level was significantly decreased to the fasting plasma glucose range. There were no confirmed hypoglycemic episodes in either group during the 4-week study period. CONCLUSIONS: After switching from basal insulin, the IDegAsp dose can be uptitrated by 60% based on fasting plasma glucose data. However, monitoring of postprandial glucose should be considered before further uptitration of IDegAsp.