Biphasic Insulin Lispro Research Articles

Assessment the equivalence of the bioanalogue insulin lizpro biphasic 25 (Geropharm-bio, Russia) and Humalog® Mix 25 (Lilly France, France) using the euglycemic hyperinsulinum clamp method on healthy volonters

Background: Modern medicine requires use of effective antidiabetic drugs that can imitate the natural profile of insulin in the body of patients with diabetes mellitus. Examples of such preparations include biphasic insulin lispro, which is a mixture of insulin lispro ultra-short action and insulin lispro protamine suspension with prolonged effect. The clinical trials (CT) program for biosimilar insulins contains pharmacology studies: pharmacokinetics (PK), pharmacodynamics (PD) and clinical safety studies.
 Aims: To demonstrate Biphasic Insulin Lispro 25, suspension for subcutaneous administration, 100 U/ml (GEROPHARM-Bio, Russia) and Humalog Mix 25, suspension for subcutaneous administration, 100 U/ml (Lilly France, France) have comparable pharmacokinetic profiles under conditions of hyperinsulinemic euglycemic clamp (HEC) in healthy volunteers.
 Materials and methods: The study was conducted on 48 healthy men aged between 18 to 50 years. This was a double-blind, randomized, crossover study of comparative pharmacokinetics of drugs. The investigational products (IP) were administered before the clamp in a single dose of 0.4 U/kg subcutaneously in the abdominal wall. Regular blood sampling was performed during the study. The insulin concentrations in the samples were determined using an ELISA method. The results of the determination were used to calculate the PK parameters and construct the concentration-time curves. Adjust glucose infusion rates were based on blood glucose measurements. These data were used to calculate the PD parameters.
 Results: Our results demonstrated that Biphasic Insulin Lispro 25 and Humalog Mix 25 have comparable PK and PD profiles under conditions of HEC in healthy volunteers. The confidence intervals for the ratio of the geometric mean for Cins.max and AUCins.012 were 87.7599.90% and 83.7696.98% respectively, which were well within 80125% limits for establishing comparability.
 Conclusions: Biphasic Insulin Lispro 25 and Humalog Mix 25 are equivalent based on this CT applying the HEC technique in healthy volunteers.

Association between mild and severe hypoglycemia in people with type 2 diabetes initiating insulin

AimsPrimary objective: Identify risk factors associated with severe hypoglycemia (SH) and investigate the association between mild hypoglycemia and SH in people with type 2 diabetes starting insulin. Secondary objectives: Investigate the association of demographics and clinical factors with SH incidence. MethodsIntegrated trial database data were obtained for 3 randomized controlled trials that included insulin-naïve people with type 2 diabetes initiating basal (insulin glargine) versus biphasic (insulin lispro mixture) insulin. Standard definitions were used for SH; mild hypoglycemia was defined as all non-SH. Cox regression identified risk factors associated with SH and the correlation between SH and mild hypoglycemia. ResultsData were pooled (N=2931). During 24–48weeks' treatment, 2127 (72.6%) participants experienced ≥1 mild hypoglycemic event but no SH (mean mild hypoglycemia rate=2.33/month). 56 participants (1.9%) experienced ≥1 SH event plus mild hypoglycemia (mean mild hypoglycemia rate=3.95/month); 748 participants (25.5%) had no hypoglycemia. Among factors tested, only mild hypoglycemia rate/month was associated with SH. SH risk was higher (HR=4.24; 95%CI=2.57–6.99;p<0.0001) for participants experiencing multiple mild hypoglycemic events/month compared with those experiencing ≤1 mild hypoglycemic event/month. ConclusionsMild hypoglycemia may predict the first SH event, which is important because SH is a strong and consistent risk factor for morbidity/mortality.

Systematic literature review of use of blood glucose monitoring in phase III clinical studies of insulin analogs.

BackgroundSafe and effective insulin therapy for diabetes mellitus requires initial dose titration and regular adjustments based on blood glucose (BG) monitoring. Our objective was to explore the use of BG measurement in phase-III clinical studies of insulin analogs. These studies provide safety and efficacy information for regulatory authorities and are the basis for insulin analog regulatory approval.MethodsA systematic review of phase-III studies of rapid-acting insulin analogs (insulin lispro, insulin aspart and insulin glulisine) and pre-mixed insulin analogs (biphasic insulin aspart and insulin lispro mix) was conducted. Studies were identified using manufacturers’ databases. Search for reports was performed in Medline and registry of clinical trials (clinicaltrials.gov). The European Medicines Agency was contacted to provide Clinical Study Reports.ResultsForty-five studies were included. Regular BG measurements were reported in 100 % of the studies and were performed by either self-monitoring of blood glucose (SMBG) alone in 84 %, laboratory alone in 7 %, and both SMBG and laboratory in 9 % of studies. In total, 93 % of the studies reported SMBG. Most studies (91 %) reported insulin therapy adjustments based on BG measurements.ConclusionsThe findings suggest that BG monitoring and specifically SMBG are co-dependent technologies with insulin analogs. BG measurement is used in most phase-III registration studies for establishing safe and efficacious insulin administration and is recommended in the insulin labels. The indispensable role of SMBG in treatment of insulin-dependent patients should receive attention from health care payers to assess and reimburse SMBG along with insulin to avoid adverse events from inappropriate insulin administration and associated costs.

Efficacy and safety of biphasic insulin aspart and biphasic insulin lispro mix in patients with type 2 diabetes: A review of the literature.

Type 2 diabetes (T2D) represents an escalating burden worldwide, particularly in China and India. Compared with Caucasians, Asian people with diabetes have lower body mass index, increased visceral adiposity, and postprandial glucose (PPG)/insulin resistance. Since postprandial hyperglycemia contributes significantly to total glycemic burden and is associated with heightened cardiovascular risk, targeting PPG early in T2D is paramount. Premixed insulin regimens are widely used in Asia due to their convenience and effectiveness. Data from randomized controlled trials and observational studies comparing efficacy and safety of biphasic insulin aspart 30 (BIAsp 30) with biphasic insulin lispro mix (LM 25/50) and versus other insulin therapies or oral antidiabetic drugs (OADs) in T2D demonstrated that BIAsp 30 and LM 25/50 were associated with similar or greater improvements in glycemic control versus comparator regimens, such as basal–bolus insulin, in insulin-naÏve, and prior insulin users. Studies directly comparing BIAsp 30 and LM 25 provided conflicting glycemic control results. Safety data generally showed increased hypoglycemia and weight gain with premixed insulins versus basal–bolus insulin or OADs. However, large observational trials documented improvements in glycated hemoglobin, PPG, and hypoglycemia with BIAsp 30 in multi-ethnic patient populations. In summary, this literature review demonstrates that premixed insulin regimens are an appropriate and effective treatment choice in T2D.

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.

A UK Analysis of the Cost-Effectiveness of Humalog Mix75/25 and Mix50/50 Versus Long-Acting Basal Insulin

As healthcare spending on diabetes and its complications continues to rise, the optimization of prescribed insulin regimens is becoming increasingly important from both clinical and economic perspectives. The aim of the present study was to evaluate the cost-effectiveness of 75/25 biphasic insulin lispro and 50/50 biphasic insulin lispro (Humalog® Mix75/25 and Humalog® Mix50/50, respectively; Eli Lilly and Company, Indianapolis, IN, USA) compared with a long-acting analog insulin regimen in patients with type 2 diabetes. A published and validated computer simulation model of diabetes was used to evaluate the cost-effectiveness of 75/25 and 50/50 biphasic insulin lispro versus a long-acting analog insulin (insulin glargine) from the perspective of a healthcare payer in the UK. Treatment effects in terms of glycated hemoglobin (HbA1c) benefits were taken from a recent meta-analysis. Direct medical costs including pharmacy, complication, and patient management costs were obtained from published sources. All costs were expressed in 2008 British pounds sterling (GBP), and future costs and clinical benefits were discounted at 3.5% per annum. Sensitivity analyses were performed. 75/25 and 50/50 biphasic insulin lispro were associated with improvements in life expectancy of 0.09 and 0.13 years, respectively, improvements in quality-adjusted life expectancy of 0.09 quality-adjusted life years (QALYs) and 0.12 QALYs, respectively, and reductions in cost of GBP 1,217 and GBP 430, respectively, when compared with long-acting analog insulin. Based on a recently published meta-analysis, biphasic analog insulins are likely to improve clinical outcomes and reduce costs versus long-acting analog insulins in the longterm treatment of patients with type 2 diabetes in the UK.

A long-term analysis evaluating the cost-effectiveness of biphasic insulin lispro mix 75/25 and mix 50/50 versus long-acting basal insulin analogs in the United States

Objective:To evaluate the cost-effectiveness of biphasic insulin lispro mix 75/25 (LM75/25) and mix 50/50 (LM50/50) compared with a long-acting analog insulin (LAAI) regimen from the perspective of a US healthcare payer.Methods:A published computer simulation model of diabetes was used to evaluate the cost-effectiveness of LM75/25 and LM50/50 vs a LAAI (insulin glargine) from the perspective of a US healthcare payer. Treatment effects in terms of HbA1c benefits were taken from a recent meta-analysis. Direct medical costs including pharmacy, complication, and patient management costs were obtained from published sources. All costs were expressed in 2010 US dollars and future costs and clinical benefits were discounted at 3% per annum. Sensitivity analyses were performed.Results:LM75/25 and LM50/50 were associated with improvements in life expectancy of 0.08 and 0.09 years, improvements in quality-adjusted life expectancy of 0.07 quality-adjusted life years (QALYs) and 0.08 QALYs and increases in cost of US$ 1724 and US$ 1720, respectively, when compared with LAAI.Limitations:The base case analysis did not capture mild or serious hypoglycemia on the grounds that the hypoglycemia rate odds ratios failed to reach statistical significance in the meta-analysis. In addition, the baseline cohort characteristics were based on an insulin-naïve population, as opposed to the cohorts in the meta-analysis, which were heterogeneous with regard to insulin treatment history.Conclusions:Based on a recently published meta-analysis, biphasic analog insulins are likely to improve clinical outcomes and reduce costs vs LAAIs in the long-term treatment of type 2 diabetes patients in the US.

Improved glycaemic control with reduced hypoglycaemic episodes and without weight gain using long-term modern premixed insulins in type 2 diabetes

The primary goal of the study was to evaluate retrospectively efficacy of long-term modern premixed insulin (MPI) administration. The secondary aims were to monitor weight gain, hypoglycaemia and compliance during MPI therapy. One hundred and fifteen outpatients with type 2 diabetes (64 male patients, 51 female patients; mean age 62.4±12.2 years; mean duration of diabetes 10±8 years; mean weight 84.3±14.8 kg) were included in this study. Patients were prescribed one of three MPIs thrice-daily: biphasic insulin lispro 25, biphasic insulin lispro 50, or biphasic insulin aspart 30. Metformin was combined with MPI in 81 patients. Data prior to and during MPI treatment were retrieved from computerised patient medical files. After a mean treatment period of 2.9±0.9 years, mean A1C levels and fasting blood glucose decreased from 8.7±1.4% and 193±59 mg/dl to 7.3±1.1% and 141±41 mg/dl (p<0.001 for both), respectively. Thirty-six per cent of the cohort achieved target A1C level of ≤7%. Serum triglycerides decreased from 183±109 mg/dl to 151±76 mg/dl (p<0.001). Weight did not change during MPI treatment. Frequency of minor hypoglycaemic episodes decreased significantly during MPI administration. No major hypoglycaemic event was reported. Number of incompliant patients decreased significantly from 39 to 25 (p=0.001) during MPI treatment. Modern premixed insulins represent an effective and safe long-term therapy for patients with type 2 diabetes. Specifically, the regimen of thrice-daily injections combined with metformin is a viable treatment option.

Case Series: Premixed Insulin Dosing in Actual Practice: Two-Thirds in AM, One-Third in PM, or Half and Half?

Initiation of insulin in type 2 diabetic patients failing to meet glycemic targets may include addition of either intermediate- or long-acting basal insulin or a biphasic premixed insulin that incorporates both basal and bolus insulins. Dual-acting basal/bolus insulin preparations are administered before meals to improve postprandial glucose levels and provide sustained glucose control throughout the dosing interval. Premixed insulins increase the convenience and acceptability of insulin use by type 2 diabetic patients who are not willing to take on or are not yet candidates for intensive basal/bolus insulin therapy.1,2 The conventional initial approach to dosing premixed insulins (biphasic insulin aspart 70/30, biphasic insulin lispro 75/25, or regular/NPH 70/30) still cited in medical texts and used in general practice is to prescribe a ratio of two-thirds of the total daily insulin dose in the morning before breakfast and one-third in the evening before dinner.3-5 Health care providers in nonspecialty settings may be less likely to use ratios other than two-thirds/one-third because of concerns regarding the safety and effectiveness of a regimen that does not follow this conventional approach. Yet, it is difficult to find practical evidence to guide providers in using a different premixed insulin regimen. After an extensive literature search of published clinical trials of premixed insulins, the authors were unable to reliably determine the ratios used in studies of type 2 diabetic patients in which premixed insulins were compared to each other or compared to basal or bolus insulins alone. No studies examined the actual prescribing patterns of the premixed insulins when used in a realistic clinical specialty practice setting in which endocrinologists use more treat-to-target approaches for rapid dose titration of insulin. This retrospective, observational, descriptive study was designed to examine the use of premixed insulins in a community-based endocrinology practice and …

Comparison of twice‐daily injections of biphasic insulin lispro and basal‐bolus therapy: glycaemic control and quality‐of‐life of insulin‐naïve type 2 diabetic patients

The aim of this study was to evaluate twice-daily injections of biphasic insulin lispro vs. basal-bolus (BB) therapy with regard to quality-of-life (QOL) and glycaemic control in insulin-naïve type 2 diabetic patients. Twenty-eight patients with type 2 diabetes were randomized to receive either twice-daily 50/50 premixed insulin lispro (Mix50 group) or BB (NPH insulin at bedtime and preprandial insulin lispro) therapy (BB group) for 12 weeks. Glycated haemoglobin (HbA1C), 1,5-anhydroglucitol (1,5-AG), blood plasma glucose level, body mass index (BMI), daily total insulin dosage and insulin therapy-related QOL (ITR-QOL) were studied. ITR-QOL was significantly better in the Mix50 than in the BB group (103.1 +/- 9.8 vs. 90.6 +/- 19.4; p < 0.05). HbA(1c) improved in both groups (from 11.1 +/- 2.1 to 6.9 +/- 1.0% with Mix50 vs. from 11.0 +/- 2.3 to 6.6 +/- 0.8% with BB therapy). These results might suggest that twice-daily injections of premixed rapid-acting insulin analogue therapy could achieve good glycaemic control and better QOL compared with BB therapy in insulin-naïve type 2 diabetes.

Efficacy of biphasic insulin aspart in patients with type 2 diabetes

Background: It is estimated that 39% of people withdiabetes worldwide who use insulin are prescribed premixes, largely because of the practical advantages of addressing both prandial and basal insulin needs with a single product. Rapid-acting premixed insulin analogues such as biphasic insulin aspart 30 (BIAsp 30 [30% soluble insulin aspart and 70% protamine-crystallized insulin aspart], NovoLog® Mix 70/30, Novo Nordisk, Bagsvaerd, Denmark) have been developed recently to overcome the pharmacokinetic limitations of regular human insulin used in the most commonly prescribed premix, biphasic human insulin 30 (BHI 30, 30% human insulin and 70% neutral protamine Hagedorn [NPH] insulin). It would be expected that these pharmacokinetic improvements would enhance clinical performance. However, the efficacy of BIAsp 30 compared with other common treatment regimens has not yet been systematically reviewed. Objective: The aim of this paper is to review currentdata on the efficacy of BIAsp 30 in comparison with other treatment strategies in type 2 diabetes, including oral antidiabetic drugs (eg, metformin, sulfonylureas, meglitinides, thiazolidinediones), conventional insulins (eg, BHI 30, NPH insulin), and other analogue insulins (eg, insulin glargine, biphasic insulin lispro 25 [Mix 25, 25% biphasic insulin lispro and 75% protaminated lispro]). The focus will be on comparative efficacy (le, postprandial glucose [PPG], blood glucose profiles, and glycosylated hemoglobin [HbA 1c]).). Methods: We identified human clinical studies publishedthrough February 2005 involving BIAsp 30 in patients with type 2 diabetes by performing a MEDLINE search (key words: biphasic insulin aspart, BIAsp 30, biphasic insulin, and premixed insulin). Additional papers were identified by assessing (1) the reference lists in these studies, (2) published conference proceedings, and (3) our reference files. A total of 21 relevant papers were retrieved: 13 were published as full manuscripts, 1 as a short communication, 5 as abstracts, and 1 as a poster. One paper is currently in press. Novo Nordisk supplied data from an unpublished trial (Study 1536, 2004), as well as data from a trial published in abstract form only (Study 1269, 2002). Results: A regimen of BIAsp 30 BID, at breakfast and dinner, provides improved PPG control compared with BHI 30 BID, NPH BID, and insulin glargine OD for patients with type 2 diabetes. Fasting plasma glucose (FPG) with BIAsp 30 was not significantly different from FPG with insulin glargine; however, FPG was higher with BIAsp 30 than with NPH. BIAsp 30 prevented excessive PPG excursions whether it was injected at the beginning of a meal or ≤15 minutes after starting a meal. BIAsp 30 was not associated with an increased risk of major hypoglycemia compared with other insulin regimens used in the studies reviewed. The incidence of minor hypoglycemic events with BIAsp 30 varied across studies but occurred with frequency or risk similar to BHI 30, Mix 25, or NPH. Treat-to-target trials reported that BIAsp 30 can be used to intensify insulin therapy and to reach the glycemic target recommended by the American Diabetes Association (ie, HbA 1c <7.0%). One study reported a greater lowering of postprandial triglyceride levels with BIAsp 30 than with BHI 30. Conclusions: BIAsp 30 BID can reduce PPG levelsto a greater extent than other common treatment regimens, including basal insulin OD. Using BIAsp 30, even once daily, may allow some patients to reach glycemic targets with a degree of convenience and tolerability that may not be achievable with other treatment regimens.

Biphasic insulin aspart 30: Literature review of adverse events associated with treatment

Background: Biphasic insulin aspart 30 (BIAsp 30 [30% soluble, rapid-acting insulin aspart and 70% protamine-bound insulin aspart], NovoLog Mix® 70/30, Novo Nordisk, Bagsvaerd, Denmark), a premixed insulin analogue, addresses both the prandial and basal aspects of glucose regulation when used once or twice daily in patients with type 1 or type 2 diabetes. It provides overall glycemic control similar to biphasic human insulin 30 (BHI 30, 30% human insulin and 70% neutral protamine Hagedorn [NPH] insulin) in patients with type 1 or type 2 diabetes. Objective: The aim of this review was to evaluatethe safety profile associated with BIAsp 30 in patients with type 1 or type 2 diabetes versus that of comparator insulin products, including BHI 30 and biphasic insulin lispro 25 (Mix 25 [25% biphasic insulin lispro and 75% protaminated lispro], Humalog® Mix 75/25, Eli Lilly and Company, Indianapolis, Indiana), together with the basal insulins, including NPH insulin and insulin glargine (Lantus®, Sanofi-Aventis Pharmaceuticals, Paris, France). Methods: Data from human clinical studies publishedin peer-reviewed journals or as conference proceedings that reported safety results in patients with type 1 or type 2 diabetes who were treated with BIAsp 30 versus comparator insulins were evaluated. To locate the appropriate articles, a MEDLINE search was performed for all years up to February 2005, using the following key words: biphasic insulin aspart, BIAsp 30, biphasic insulin, and premixed insulin. Additional papers were identified by examining the reference lists in these papers as well as our own personal reference files. Results from 17 publications were analyzed. The analysis included >2600 patients with type 2 diabetes (mean [range] age, 58 [36–70] years; duration of diabetes, 11.8 [9–17] years; and baseline glycosylated hemoglobin [HbA1,], 8.6% [7.5%–9.9%]). It also included 104 patients with type 1 diabetes (mean [range] age, 44.5 [30–58] years; duration of diabetes, 16 [2–30] years; and baseline HbA 1c, 8.4% [7.2%–10.4%]). Results: Hypoglycemia occurred in 43% to 57% of patients receiving BIAsp 30 versus 32% to 57% of patients receiving BHI 30 and 28% of patients receiving NPH insulin. Major hypoglycemic events were uncommon in most studies; but when they did occur, they were reported less frequently in patients receiving BIAsp 30 (2%–8% of patients) than in patients receiving BHI 30 (2%–14% of patients). Furthermore, patients treated with BIAsp 30 were at lower risk of experiencing minor nocturnal hypoglycemia than patients receiving comparator insulin; in 1 study, the relative risk (BIAsp 30 vs BHI 30) was calculated to be 0.63 (95% CI, 0.37 to 1.09). The adverse event (AE) profile, weight gain during treatment, and formation of cross-reactive antibodies were not different between BIAsp 30 and BHI 30. AEs were reported in 36% to 90% of patients receiving BIAsp 30, 38% to 88% of patients receiving BHI 30, and 51% of patients receiving Mix 25. The use of oral antidiabetic drugs in combination with BIAsp 30 did not alter the safety profile of BIAsp 30. Conclusion: The flexible and convenient treatmentregimen offered by BIAsp 30, together with its ability to improve postprandial glucose control, is associated with a safety profile comparable to that of BHI 30 and NPH insulin, with a lower risk of major and nocturnal hypoglycemic events.

Randomized, multinational, open-label, 2-period, crossover comparison of biphasic insulin aspart 30 and biphasic insulin lispro 25 and pen devices in adult patients with type 2 diabetes mellitus

Objective: The goal of this study was to compare the efficacy and safety profiles of biphasic insulin aspart 30 (30% soluble insulin aspart and 70% protaminated insulin aspart [BIAsp 30]) and biphasic insulin lispro 25 (25% soluble insulin lispro and 75% neutral protamine lispro [Mix25]) used in a BID injection regimen in patients with type 2 diabetes mellitus (DM). Also assessed was patients' preference for pen device—the NovoMix® 30 FlexPen®/NovoLog® Mix 70/30 FlexPen® (FlexPen) versus the Humalog® Mix25 TM Pen/Humalog® Mix75/25 TM Pen (Humalog Pen). Methods: Patients with type 2 DM receiving current insulin treatment were randomized to a multinational, multicenter, open-label, 2-period, crossover comparison of BIAsp 30 and Mix25. Efficacy (by analyses of variance) and safety profiles were assessed after 12 weeks of treatment. Patients' preference for pen device was assessed by questionnaires. Results: A total of 137 patients were randomized to treatment; 4 were withdrawn during the 2-week run-in treatment with biphasic human insulin 30. The mean (SD) characteristics of the remaining 133 patients (79 men, 54 women) were as follows: age, 62.3 (9.2) years; body mass index, 28.1 (3.9) kg/m 2; and glycosylatd hemoglobin (HbA 1c), 8.5% (1.1). Glycemic control was assessed by the measurement of HbA 1c after 12 weeks of treatment. Treatment with BIAsp 30 was noninferior to treatment with Mix25 (upper limit of 90% CI for estimated difference [BIAsp 30 - Mix25] was <0.4%). Self-monitored blood glucose levels were comparable ( P = NS). Adverse-event profiles were similar between treatments, as was the incidence of hypoglycemic episodes (0.69 episode/mo with BIAsp 30 and 0.62 episode/mo with Mix25, P = 0.292). For all device features assessed, the FlexPen consistently received higher scores (all P < 0.005). A total of 9.0% of patients experienced problems with the FlexPen, compared with 32.4% with the Humalog Pen ( P < 0.001). Furthermore, 74.6% preferred to continue using the FlexPen, whereas 14.3% preferred the Humalog Pen ( P < 0.001). Conclusions: In this study, glycemic control with BIAsp 30 and Mix25 was found to be comparable in these patients with type 2 DM. Safety profiles were similar for both regimens. Patients preferred and experienced fewer problems with the FlexPen than the Humalog Pen.