Real-world study of ethnic differences in glycaemic control and clinical characteristics among insulin-naïve people with type 2 diabetes initiating biphasic insulin aspart 30/70: A retrospective, observational cohort study in England.

AIMS: This study investigated the ethnic differences in glycaemic levels and clinical characteristics among insulin-naïve people with type 2 diabetes (T2D) initiating biphasic insulin aspart 30/70 (BIAsp 30) in primary practice in England. MATERIALS AND METHODS: Retrospective, observational cohort study utilizing data from the Clinical Practice Research Datalink Aurum database, including White, South Asian, Black and Chinese insulin-naïve adults with T2D, initiating BIAsp 30. The index date was that of the first BIAsp 30 prescription. Endpoints included change in glycated haemoglobin (HbA1c) and body mass index (BMI) 6 months post index. RESULTS: In total, 11 186 eligible people were selected (9443 White, 1116 South Asian, 594 Black, 33 Chinese). HbA1c decreased across all subgroups 6 months post index: estimated %-point changes [95% CI of -2.32 (-2.36; -2.28) (White); -1.91 (-2.02; -1.80) (South Asian); -2.55 (-2.69; -2.40) (Black); and -2.64 (-3.24; -2.04) (Chinese)]. The BMI increased modestly 6 months post index in all subgroups [estimated changes (95% CI) kg/m2 : White, 0.92 (0.86; 0.99); South Asian, 0.60 (0.41; 0.78); Black, 1.41 (1.16; 1.65); and Chinese, 0.32 (-0.67; 1.30)]. In the overall population, hypoglycaemic event rates increased from 0.92 events per 100 patient-years before the index to 3.37 events per 100 patient-years post index; event numbers were too low to be analysed by subgroup. CONCLUSIONS: Among insulin-naïve people with T2D initiating BIAsp 30, clinically meaningful HbA1c reductions in all ethnicities were observed. Some ethnic groups had larger reductions than others, but differences were small. In all groups, small BMI increases were seen, with small differences observed between groups. Hypoglycaemia rates were low.

Hypoglycaemia events with iGlarLixi versus premix biphasic insulin aspart 30 (BIAsp 30) in people with type 2 diabetes advancing from basal insulin: An analysis of the SoliMix trial.

AIMS: To explore details of the incidence and rates of daytime and nocturnal hypoglycaemia, levels of hypoglycaemia, and relationship to glycated haemoglobin (HbA1c), when comparing iGlarLixi versus premixed biphasic insulin aspart 30 (BIAsp 30) in the SoliMix randomized controlled trial. MATERIALS AND METHODS: This exploratory analysis of SoliMix used logistic regression and negative binomial regression analyses to assess between-treatment differences in the incidence and rates of hypoglycaemia by time of day. A negative binomial model was used to derive estimated annualized hypoglycaemia rates as a function of HbA1c. RESULTS: iGlarLixi was associated with lower incidence and rates of American Diabetes Association Level 2 (<54 mg/dL [<3.0 mmol/L]) hypoglycaemia during both night and day versus BIAsp 30. Incidence and rates of Level 1 (<70 to ≥54 mg/dL [<3.9 to ≥3.0 mmol/L]) hypoglycaemia were also mostly shown to be reduced with iGlarLixi versus BIAsp 30. Severe (Level 3) events were too few for analysis (n = 3). iGlarLixi was associated with lower modelled event rates of Level 2 and Level 1 hypoglycaemia over a wide range of HbA1c levels versus BIAsp 30. CONCLUSIONS: These results show that the lower HbA1c levels and weight benefit seen with iGlarLixi versus premixed BIAsp 30 in people with type 2 diabetes advancing their basal insulin therapy in the SoliMix trial are also accompanied by a lower risk of hypoglycaemia at any time of day and across a broad range of HbA1c levels.

Composite cardiovascular risk and BMI affected comparative profiles of BIAsp 30 + metformin vs BIAsp 30 monotherapy: a MERIT post-hoc analysis.

We assessed whether comparative efficacy and safety of biphasic insulin aspart 30 (BIAsp 30) plus metformin versus BIAsp 30 monotherapy differed for patients with type 2 diabetes mellitus (T2DM) inadequately controlled with oral antidiabetic drugs with different cardiovascular risk scores and different body mass indexes (BMI) by performing a post hoc analysis of the randomized controlled MERIT study. In the MERIT study, eligible patients were randomized 1:1 to receive BIAsp 30 plus metformin or BIAsp 30 for 16 weeks. Patients in the 2 treatment groups were classified into "low" and "high" risk subgroups based on their GloboRisk scores and into "BMI ≤ 26 kg/m2"and "BMI > 26 kg/m2" subgroups. Primary efficacy endpoint was between-treatments comparison of HbA1c changes from baseline for these 2 sets of subgroups. Between-treatments comparisons of secondary efficacy and safety endpoints were also performed. We found that BIAsp 30 plus metformin led to significantly higher percentage of high-risk patients achieving HbA1c target < 7% than BIAsp 30 monotherapy, with an overall comparable safety profile for high-risk patients. Meanwhile, for patients with BMI ≤ 26 kg/m2, compared with BIAsp 30 monotherapy, BIAsp 30 plus metformin led to significantly higher percentages of patients achieving HbA1c target (47.83% vs 28.17%, P = 0.0165) and composite target of HbA1c < 7% without hypoglycemia or weight gain (20.29% vs 6.85%, P = 0.0187) and have a slightly better safety profile. In conclusion, for T2DM patients at high CV risk or with BMI ≤ 26 kg/m2, BIAsp 30 plus metformin was preferable to BIAsp 30 monotherapy.

Safety and effectiveness of a biosimilar biphasic insulin in the management of diabetes mellitus during routine clinical practice in Asian patients.

INTRODUCTION: Biosimilar insulins have the potential to increase access to treatment among patients with diabetes mellitus (DM), reduce treatment costs, and expand market competition. There are no published studies evaluating the performance of biosimilar insulins in routine clinical practice in Asia. This study assessed the safety and effectiveness of biphasic isophane insulin injection in Malaysian DM patients. MATERIALS AND METHODS: In this open label, single-arm, observational, post marketing study, patients received biphasic isophane insulin injection as per the Prescribing Information; and were assessed for safety (adverse events including hypoglycaemia), effectiveness (glycosylated haemoglobin [HbA1c]; fasting blood sugar, [FBS]; and patient's condition by patient and physician) over a period of 24 weeks. RESULTS: Adult male and female diabetes patients (N=119; type 2 DM, n=117) with a mean (SD) diabetes duration of 13 years were included. No new safety signals have been identified. Significant reduction in HbA1c was observed at weeks 12 and 24 (mean [SD] - baseline: 9.6% [1.9]; Week 12: 9.0% [1.7] and at Week 24: 9.1% [1.7]; p < 0.001). There were 10 serious and 9 non-serious adverse events reported in the study. Expected mild events included hypoglycaemia and injection site pruritus. However, the majority of the adverse events were non-study drug related events. No deaths were reported during the study. DISCUSSION: Biphasic isophane insulin injection was well tolerated with no new safety concerns. It was found effective in post- marketing studies conducted in routine clinical settings when administered in DM patients in this study.

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.

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.

15 Years of Experience with Biphasic Insulin Aspart 30 in Type 2 Diabetes.

Since clinical experience with biphasic insulin aspart 30 (BIAsp 30) in type 2 diabetes mellitus (T2DM) was reviewed in 2012 after 10 years of use worldwide, additional studies have been published that highlight new aspects, including use in real-world populations. Evidence from 35 new studies confirms and builds upon previous work indicating that BIAsp 30 continues to have pharmacodynamic and clinical advantages over biphasic human insulin (BHI 30), including in real-world practice with unselected populations of patients. BIAsp 30 has also been shown to be safe and efficacious as an add-on to dipeptidyl peptidase-4 (DPP-4) inhibitors. Intensification with BIAsp 30 is a safe and effective way to improve glycemic control, and titration performed by patients can achieve results that are at least comparable to those when being guided by healthcare providers. Stepwise intensification using BIAsp 30 is comparable to intensification using a basal-bolus regimen, and twice-daily BIAsp 30 provides similar glycemic control to a basal-plus regimen. Data from large observational studies, in particular, have identified patient-related characteristics that are associated with improved clinical responses, suggesting that earlier initiation and intensification of therapy is warranted. Finally, new health-economic analyses continue to confirm that BIAsp 30 is cost effective versus other therapies such as BHI 30, neutral protamine Hagedorn (NPH), or insulin glargine in both insulin-naïve and insulin-experienced patients. After 15 years of clinical use worldwide, analysis of more recent 5-year data indicates that BIAsp 30 remains a safe, effective, and simple-to-use insulin for initiation and intensification by diabetes specialists and primary care physicians in a variety of patients with T2DM.

Biphasic insulin aspart 30 treatment for people with type 2 diabetes: a budget impact analysis based in Thailand.

OBJECTIVE: To assess the financial consequences of different adoption rate of Biphasic Insulin Aspart (BIAsp) 30 instead of Biphasic Human Insulin (BHI) 30 for people with type 2 diabetes (T2DM) in Thailand from the payer's perspective. METHODS: The Excel-based International T2DM Budget Impact Model over a 3-year period was used. The cohort was the T2DM patients who received treatment from government hospitals under the Universal Health Coverage Scheme. Demographic, the adverse events, and the costs were derived from published studies in Thailand. Efficacy was based on meta-analysis. Adoption rates were assumed to increase each year. Net budget impact (NBI) and one-way sensitivity were analyzed. RESULTS: Hypoglycemia costs were lower in BIAsp 30 compared with BHI 30. The NBI per year was 26,511,269 THB (771,349 USD) for year 1, 52,181,133 THB (1,518,218 USD) for year 2, and 76,189,608 THB (2,216,747 USD) for year 3. The NBI per insulin user per year was 33.45 THB (0.97 USD), 67.27 THB (1.96 USD), 101.49 THB (2.95 USD) from year 1 to year 3, respectively Conclusions: Lower rate of hypoglycemia with BIAsp 30 than those treated with BHI 30 generates cost savings resulting in significant deduction in the additional acquisition cost of BIAsp 30. Therefore, the NBI per insulin user per year has become small.

Phase III Study on Efficacy and Safety of Triple Combination (Exenatide/Metformin/Biphasic Insulin Aspart) Therapy for Type 2 Diabetes Mellitus.

Exenatide, metformin (MET), and biphasic insulin aspart 30 (BIA30) have been widely used in the treatment of patients with type 2 diabetes mellitus (T2DM); however, each of these medications has significant adverse effects, which limit their utilization. This study aimed to evaluate the efficacy and safety of triple combination (exenatide/metformin/biphasic insulin aspart) therapy for T2DM. Two hundred patients with poorly controlled T2DM were randomly divided into the low-dose (0.5 µg exenatide, 0.05 U·kg·d BIA30, and 0.01 g MET twice daily) and normal-dose (2 µg exenatide, 0.2 U·kg·d BIA30, and 0.05 g MET twice daily) groups for 48 weeks of treatment. Of note, 82 and 90 individuals from the low-dose and normal-dose groups, respectively, completed the study. The levels of adiponectin, C-reactive protein, tumor necrosis factor-α, and resistin were measured. The normal-dose treatment was more effective at lowering hemoglobin A1c levels than the low-dose therapy (HbA1c changes of -2.5 ± 0.19% and -0.8 ± 0.07%, respectively) after 48 weeks. The maximum weight decrease was 0.9 kg in the low-dose group and 4.0 kg in the normal-dose group. The triple combination therapy increased the levels of insulin sensitivity and adiponectin and reduced the levels of C-reactive protein, resistin, and tumor necrosis factor-α. No significant difference in the adverse effects was found between the low-dose and normal-dose groups (P > 0.05). In conclusion, the investigated triple combination therapy for T2MD is therefore an effective and safe therapeutic strategy.

Insulin lispro 25/75 and insulin lispro 50/50 as starter insulin in Japanese patients with type 2 diabetes: subanalysis of the CLASSIFY randomized trial.

In Japan, premixed insulins are commonly used as starter insulin for type 2 diabetes. This subpopulation analysis assessed the efficacy and safety of twice-daily LM25 (25% insulin lispro/75% insulin lispro protamine) and LM50 (50% insulin lispro/50% insulin lispro protamine) as starter insulin in Japanese subjects, and compared these results with the whole-trial populations of East Asian subjects. In this subpopulation analysis of an open-label, phase 4, randomized trial (CLASSIFY), Japanese subjects received LM25 (n = 88) or LM50 (n = 84) twice-daily for 26 weeks. The primary outcome was change from baseline at Week 26 in glycated hemoglobin (HbA1c). Results for Japanese subjects were generally similar to those for the whole-trial population. Similar changes from baseline in HbA1c were observed for LM25 and LM50 groups (least squares [LS] mean difference [95% confidence interval] of LM25 - LM50 = 0.13 [-0.16, 0.41]%, 1.42 [-1.75, 4.48] mmol/mol, p = 0.388). More LM50-treated subjects than LM25-treated subjects achieved HbA1c targets of <7.0% (59.5% versus 43.2%; p = 0.034) or ≤6.5% (45.2% versus 28.4%; p = 0.027). The reduction in postprandial blood glucose concentrations after morning and evening meals was statistically significantly greater for LM50 than for LM25. The incidence of both hypoglycemia and treatment-emergent adverse events were similar between treatment groups. Both LM25 and LM50 twice daily appear to be effective and well tolerated as starter insulin, although LM50 might be more effective for Japanese type 2 diabetes patients.

Premixed insulin regimens in type 2 diabetes: pros.

Because of the increasing prevalence of type 2 diabetes, the need to intensify treatment to manage hyperglycemia is expanding. Premixed insulin regimens were designed to maximize patient convenience and reduce the number of daily injections required by providing both rapid-acting and intermediate-acting components in one formulation. Although the basal bolus insulin regimen is considered by many as "the golden standard" in reaching goals of glycemic control, proper use of intensified insulin regimens, such as basal bolus or premixed, will result in similar HbA1c reduction, hypoglycemic events, and weight gain. At the same number of daily insulin injections (2 shots/day), the premixed regimen is associated with a significant 0.2 % HbA1c decrease, as compared with the basal plus regimen (one shot of long-acting plus one shot of short-acting insulin). The choice of insulin regimen should consider the preferences, and resources of the individual and the family for adapting treatment to the patient needs. At last, the process of insulin initiation and intensification in type 2 diabetes must be carried out in the context of patient safety, minimizing the risk of hypoglycemia, weight gain, and injection burden.

Prediction of excessive weight gain in insulin treated patients with type 2 diabetes.

BACKGROUND: Weight gain is an ongoing challenge when initiating insulin therapy in patients with type 2 diabetes mellitus (T2DM). However, if prediction of insulin-associated weight gain was possible on an individual level, targeted initiatives could be implemented to reduce weight gain. The aim of the present study was to identify predictors of weight gain in insulin-treated patients with T2DM. METHODS: In all, 412 individuals with T2DM were, in addition to metformin or placebo, randomized into 18-month treatment groups with three different insulin analog treatment regimens (biphasic, aspart, detemir). Participants with excessive weight gain were defined as the group with weight gain in the 4th quartile (>6.2 kg).We developed a pattern classification method to predict individuals prone to excessive weight gain. RESULTS: Over the 18-month treatment period, median weight gain among all 412 patients was 2.4 kg (95% prediction interval [PI] -5.6, 12.4 kg), whereas median weight gain for those in the upper 4th quartile (n = 103) was 8.9 kg (95% PI 6.3, 15.2 kg). No clinical baseline data were strong predictors of excessive weight gain. However, the weight gain during the first 3 months of the trial and the subsequent dose of insulin yielded a useful predictor for weight gain at the 18-month follow-up. Combining these two predictors into a prediction model with other clinical available information produced a receiver operating characteristic area under the curve of 0.80. CONCLUSIONS: We have developed a prediction model that could help identify a substantial proportion of individuals with T2DM prone to large weight gain during insulin therapy.

Insulin degludec/insulin aspart versus biphasic insulin aspart 30 twice daily in insulin-experienced Japanese subjects with uncontrolled type 2 diabetes: Subgroup analysis of a Pan-Asian, treat-to-target Phase 3 Trial.

BACKGROUND: The present study was a subgroup analysis of a Pan-Asian Phase 3 open-label randomized treat-to-target trial evaluating insulin degludec/insulin aspart (IDegAsp) and biphasic insulin aspart 30 (BIAsp 30) in Japanese subjects with type 2 diabetes inadequately controlled on insulin. METHODS: Eligible subjects (n = 178) were randomized (2: 1) to twice-daily (b.i.d.) IDegAsp or BIAsp 30 with or without metformin for 26 weeks, titrated to a blood glucose target of between 3.9 and <5.0 mmol/L. Changes in HbA1c , the proportion of responders reaching the HbA1c target, and changes in fasting plasma glucose, nine-point self-monitored plasma glucose profiles, and body weight were assessed. RESULTS: At 26 weeks, the decrease in HbA1c was similar in both groups. Fasting plasma glucose was lower with IDegAsp than BIAsp 30 (estimated treatment difference -1.50 mmol/L; 95 % confidence interval [CI] -1.98, -1.01). Overall confirmed hypoglycemia rates were similar; the nocturnal confirmed hypoglycemia rate was lower with IDegAsp than BIAsp 30 (estimated rate ratio 0.44; 95 % CI 0.20, 0.99). No severe hypoglycemic episodes were reported. CONCLUSIONS: The results indicate that IDegAsp b.i.d. improves glycemic control and, compared with BIAsp 30, lowers the rate of nocturnal confirmed hypoglycemia.

Management of postprandial glucose: Recommended targets and treatment with biphasic insulin.

Increases in glycaemia, particularly following meals, have been independently associated with diabetes complications, most notably cardiovascular disease. Control of postprandial plasma glucose (PPG) therefore plays an important role in diabetes management. International diabetes guidelines acknowledge the value of PPG monitoring yet place relatively little emphasis on PPG control. This article considers the impact of suboptimal PPG control and current recommendations with regard to management of PPG. Specific consideration is given to the role of biphasic insulins, one of the treatment options recognised by the International Diabetes Federation as preferentially lowering PPG levels.

Biphasic insulin Aspart 30 vs. NPH plus regular human insulin in type 2 diabetes patients; a cost-effectiveness study.

BACKGROUND: The aim of this study was to compare the efficacy, safety, costs, and cost-effectiveness of biphasic insulin aspart 30 (BIAsp 30) with NPH plus regular human insulin (NPH/Reg) in patients with type 2 diabetes mellitus (T2DM). METHODS: It was a Single-center, parallel-group, randomized, clinical trial (Trial Registration: NCT01889095). One hundred and seventy four T2DM patients with poorly controlled diabetes (HbA1c ≥ 8 % (63.9 mmol/mol)) were randomly assigned to trial arms (BIAsp 30 and NPH/Reg) and were followed up for 48 weeks. BIAsp 30 was started at an initial dose of 0.2-0.6 IU/Kg in two divided doses and was titrated according to the glycemic status of the patient. Similarly, NPH/Reg insulin was initiated at a dose of 0.2-0.6 IU/Kg with a 2:1 ratio and was subsequently titrated. Level of glycemic control, hypoglycemic events, direct and indirect costs, quality adjusted life year (QALY) and incremental cost-effectiveness ratio have been assessed. RESULTS: HbA1c, Fasting plasma glucose (FPG), and two-hour post-prandial glucose (PPG) were improved in both groups during the study (P < 0.05 for all analyses). Lower frequencies of minor, major, and nocturnal hypoglycemic episodes were observed with BIAsp 30 (P < 0.05). Additionally, BIAsp 30 was associated with less weight gain and also higher QALYs (P < 0.05). Total medical and non-medical costs were significantly lower with BIAsp 30 as compared with NPH/Reg (930.55 ± 81.43 USD vs. 1101.24 ± 165.49 USD, P = 0.004). Moreover, BIAsp 30 showed lower ICER as a dominant alternative. CONCLUSIONS: Despite being more expensive, BIAsp 30 offers the same glycemic control as to NPH/Reg dose-dependently and also appears to cause fewer hypoglycemic events and to be more cost-effective in Iranian patients with type 2 diabetes.

Comparison of exenatide with biphasic insulin aspart 30 on glucose variability in type 2 diabetes: study protocol for a randomized controlled trial.

BACKGROUND: Apart from the mean level of glycemic control, the extent of glucose excursions is another important issue to consider in type 2 diabetes mellitus (T2DM) management. Studies have showed that fluctuations of glucose seem to have more deleterious effects than sustained hyperglycemia in the development of diabetic complications as acute glucose swings activate the oxidative stress. However, until now, no randomized controlled trials have been conducted with the primary aim to evaluate glycemic fluctuation in the comparison between twice-daily exenatide and other treatment paradigms (for example, biphasic insulin aspart 30). METHODS/DESIGN: This multicenter, open-label, randomized, parallel trial includes a 1-week screening period and a 16-week treatment period. After the screening period, 150 patients with confirmed type 2 diabetes who are treated with stable, maximum-tolerated doses of metformin will be randomly assigned to one of two groups for antihyperglycemic therapies: exenatide and biphasic insulin aspart 30. The treatment with exenatide will be initiated at a low dose of 5 µg twice a day for 4 weeks and then titrated up to a standard dose of 10 ug twice a day until the completion of the study. The adjustment of insulin dose is instructed to achieve an optimal balance between glycemic control and the risk of hypoglycemia as dictated by clinical practice. The primary outcome is the absolute change of mean amplitude of glycemic excursion from baseline to week 16, which is calculated based on a real-time continuous glucose monitoring system (CGMS). DISCUSSION: This is the first randomized controlled trial using a CGMS to evaluate glycemic fluctuation between twice-daily exenatide and insulin aspart 30, which will provide beneficial evidence of exenatide usage in patients with T2DM. TRIAL REGISTRATION NUMBER: NCT02449603 . Date of registration: 11 May 2015.

Blood Glucose Fluctuations in Type 2 Diabetes Patients Treated with Multiple Daily Injections.

To compare blood glucose fluctuations in type 2 diabetes mellitus (T2DM) patients were treated using three procedures: insulin intensive therapy which is continuous subcutaneous insulin infusion (CSII), MDI3 (three injections daily), and MDI4 (four injections daily). T2DM patients were hospitalized and were randomly assigned to CSII, aspart 30-based MDI3, and glargine based MDI4. Treatments were maintained for 2-3 weeks after the glycaemic target was reached. After completing the baseline assessment, 6-day continuous glucose monitoring (CGM) was performed before and after completion of insulin treatment. Treatment with CSII provided a greater improvement of blood glucose fluctuations than MDI (MDI3 or MDI4) therapy either in newly diagnosed or in long-standing T2DM patients. In long-standing diabetes patients, the MDI4 treatment group had significantly greater improvement of mean amplitude glycemic excursion (MAGE) than the MDI3 treatment group. However, in patients with newly diagnosed diabetes, there were no significant differences in the improvement of MAGE between MDI3 and MDI4 groups. Glargine based MDI4 therapy provided better glucose fluctuations than aspart 30-based MDI3 therapy, especially in long-standing T2DM patients, if CSII therapy was not available.

Lower rates of hypoglycemia during maintenance treatment with insulin degludec/insulin aspart versus biphasic insulin aspart 30: a combined analysis of two Phase 3a studies in type 2 diabetes.

BACKGROUND: Insulin degludec/insulin aspart (IDegAsp) is a soluble coformulation of the basal analog insulin degludec and the rapid-acting prandial insulin aspart in a single injection. The present combined analysis of two Phase 3a trials compared the incidence of hypoglycemia in participants treated twice daily with IDegAsp or biphasic insulin aspart 30 (BIAsp 30). METHODS: Hypoglycemia data were analyzed from two similarly designed randomized controlled open-label treat-to-target Phase 3a clinical trials of adults with type 2 diabetes (T2D). Participants were treated twice daily with IDegAsp or BIAsp 30, with breakfast and their main evening meal. RESULTS: Over 26 weeks, the rates of overall confirmed, nocturnal confirmed and severe hypoglycemic events were 19%, 57%, and 39% lower, respectively, with IDegAsp (n = 504) than BIAsp 30 (n = 364); estimated rate ratios were 0.81 (95% confidence interval [CI] 0.67, 0.98; P = 0.0341), 0.43 (95% CI 0.31, 0.59; P = 0.0001), and 0.61 (95% CI 0.26, 1.45; P = NS). The between-treatment differences were more pronounced during the maintenance period (≥16 weeks); compared with BIAsp 30, rates of overall confirmed, nocturnal confirmed and severe hypoglycemic events with IDegAsp were 0.69 (95% CI 0.55, 0.87; -31%; P = 0.0015); 0.38 (95% CI 0.25, 0.58; -62%; P < 0.0001), and 0.16 (95% CI 0.04, 0.59; -84%; P = 0.0061), respectively. CONCLUSIONS: Compared with BIAsp 30 twice daily, IDegAsp twice daily provided similar improvements in glycemic control with a lower risk of hypoglycemia, particularly nocturnal hypoglycemia, in subjects with T2D previously treated with insulin.

Twice-daily insulin degludec/insulin aspart provides superior fasting plasma glucose control and a reduced rate of hypoglycaemia compared with biphasic insulin aspart 30 in insulin-naïve adults with Type 2 diabetes.

AIM: To evaluate the efficacy and safety of twice-daily insulin degludec/insulin aspart vs. twice-daily biphasic insulin aspart 30 in people with Type 2 diabetes mellitus who were naïve to insulin. METHODS: In this 26-week, multinational, open-label, controlled, two-arm, parallel-group, treat-to-target trial, participants [mean (± sd) age 58.9 (±8.9) years, duration of diabetes 9.5 (±5.9) years, HbA1c 68 (±8.7) mmol/mol or 8.4 (±0.8)% and BMI 31.2 (±4.2) kg/m(2) ) were randomized (1:1) to insulin degludec/insulin aspart (n = 197) or biphasic insulin aspart 30 (n = 197), administered with breakfast and the main evening meal, titrated to a self-monitored plasma glucose target > 3.9 and ≤ 5.0 mmol/l. RESULTS: The mean HbA1c was reduced to 49 mmol/mol (6.6%) with insulin degludec/insulin aspart and 48 mmol/mol (6.5%) with biphasic insulin aspart 30. Insulin degludec/insulin aspart achieved the prespecified non-inferiority margin (estimated treatment difference 0.02%; 95% CI -0.12, 0.17). Insulin degludec/insulin aspart was superior in lowering fasting plasma glucose (estimated treatment difference -1.00 mmol/l; 95% CI -1.4, -0.6; P < 0.001) and reducing overall and nocturnal confirmed hypoglycaemia at a similar overall insulin dose compared with biphasic insulin aspart 30. Similar proportions of participants in each arm experienced severe hypoglycaemia. Adverse events were equally distributed. CONCLUSIONS: Consistent with previous findings, insulin degludec/insulin aspart twice daily effectively improved long-term glycaemic control, with superior reductions in FPG, and significantly less overall and nocturnal confirmed hypoglycaemia compared with biphasic insulin aspart 30 in people with Type 2 diabetes who were insulin-naïve.

Intensifying insulin regimen after basal insulin optimization in adults with type 2 diabetes: a 24-week, randomized, open-label trial comparing insulin glargine plus insulin glulisine with biphasic insulin aspart (LanScape).

AIM: To test the hypothesis that a 'basal plus' regimen--adding once-daily main-meal fast-acting insulin to basal insulin once daily--would be non-inferior to biphasic insulin twice daily as assessed by glycated haemoglobin (HbA1c) concentration (predefined as ≤0.4%), but would provide superior treatment satisfaction. METHODS: This open-label trial enrolled adults to an 8- or 12-week run-in period, during which oral therapies except metformin were stopped and insulin glargine dose was titrated. Those with fasting glucose <7 mmol/l but HbA1c >7% (53 mmol/mol) were randomized to insulin glargine/glulisine once daily (n = 170) or insulin aspart/aspart protamine 30/70 twice daily (n = 165) for 24 weeks, with dose titration to glucose targets using standardized algorithms. RESULTS: For HbA1c, the basal plus regimen was non-inferior to biphasic insulin (least squares mean difference, 0.21%, upper 97.5% confidence limit 0.38%) meeting the predefined non-inferiority margin of 0.4%. Treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire change version and Insulin Treatment Satisfaction Questionnaire total scores) significantly favoured basal plus. No difference was observed between the basal plus and the biphasic insulin groups in responders (HbA1c <7%, 20.6 vs 27.9%; p = 0.12), weight gain (2.06 vs 2.50 kg; p = 0.2), diabetes-specific quality of life (Audit of Diabetes-Dependent Quality of Life average weighted impact (AWI) score) and generic health status (five-dimension European Quality of Life questionnaire). Overall hypoglycaemia rates were similar between groups (15.3 vs 18.2 events/patient-year; p = 0.22); nocturnal hypoglycaemia was higher with the basal plus regimen (5.7 vs 3.6 events/patient-year; p = 0.02). CONCLUSION: In long-standing type 2 diabetes with suboptimal glycaemia despite oral therapies and basal insulin, the basal plus regimen was non-inferior to biphasic insulin for biomedical outcomes, with a similar overall hypoglycaemia rate but more nocturnal events.

Clinical use and efficacy of biphasic insulin lispro 50/50 in people with insulin treated diabetes - a nationwide evaluation of clinical practice.

OBJECTIVES: This study aims to investigate the metabolic effects of biphasic insulin lispro 50/50 in routine clinical practice. A total of 229 patients who were ≥18 years old with diabetes, newly treated with biphasic insulin lispro 50/50, were sourced from six secondary care services in England. METHODS: Detailed clinical parameters were compared at baseline, and 3 and 6 months post-initiation. Responders was defined as those with HbA1c <7.5% (58 mmol/mol) and/or an HbA1c reduction of >1% (11 mmol/mol) at 6 months. RESULTS: HbA1c showed significant reduction: -0.93% (-10 mmol/mol) and -1.2% (-13 mmol/mol) at 3 and 6 months respectively, while no significant change was noted for all the other parameters. When analyzed according to frequencies of injections/day, the greatest reduction was observed with the three times a day regimen (-1.0% [-11.0 mmol/mol] and -1.3% [-14.6 mmol/mol] at 3 and 6 months respectively). HbA1c reduction was greatest in the group who previously received a basal-bolus insulin regimen: (-0.8% [-9.0 mmol/mol] and -1.5% [-16.2 mmol/mol] at 3 and 6 months respectively). Reduction in weight was observed at 3 months (-1.8 kg ± 4.3) only for those who were previously on a basal-bolus insulin regimen. Insulin doses increased following conversion to biphasic insulin lispro 50/50, irrespective of the types of insulin used prior to biphasic insulin lispro 50/50, but this was not associated with weight gain. The independent predictors of response to biphasic insulin lispro 50/50 were baseline HbA1c, Caucasian, presence of nephropathy, prior use of basal-bolus insulin and prior use of other premixed combination. CONCLUSION: Biphasic insulin lispro 50/50 is therefore an effective therapeutic option for achieving glycemic control in patients with suboptimal HbA1c levels, especially among those who were previously on a basal-bolus insulin regimen and those who received it three times daily, with a neutral effect on weight parameters. LIMITATIONS: This was a retrospective study of routine clinical practice and is therefore limited by allocation bias and some missing data. Information on rates of hypoglycemia and quality of life are not available.