Effects of Exenatide and Humalog Mix25 on Fat Distribution, Insulin Sensitivity, and ß-Cell Function in Normal BMI Patients with Type 2 Diabetes and Visceral Adiposity.

In China, most normal BMI (body mass index of ≥18.5 to <25 kg/m2) adults with type 2 diabetes (T2DM) exhibit visceral adiposity. This study compared the effects of exenatide and humalog Mix25 on normal BMI patients with T2DM and visceral adiposity. A total of 95 patients were randomized to receive either exenatide or humalog Mix25 treatment for 24 weeks. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were quantified by magnetic resonance imaging (MRI) and liver fat content (LFC) by liver proton magnetic resonance spectroscopy (1H MRS). Each patient's weight, waist circumference, BMI, blood glucose, insulin sensitivity, pancreatic ß-cell function, and fibroblast growth factor 21 (FGF-21) levels were measured. Data from 81 patients who completed the study (40 and 41 in the exenatide and humalog Mix25 groups, respectively) were analysed. The change in 2 h plasma blood glucose was greater in the exenatide group (P = 0.039). HOMA-IR and MBCI improved significantly after exenatide therapy (P < 0.01, P = 0.045). VAT and LFC decreased in both groups (P < 0.01 for all) but to a greater extent in the exenatide group, while SAT only decreased with exenatide therapy (P < 0.01). FGF-21 levels declined more in the exenatide group (P < 0.01), but were positively correlated with VAT in the entire cohort before (r = 0.244, P = 0.043) and after (r = 0.290, P = 0.016) the intervention. The effects of exenatide on glycaemic metabolism, insulin resistance, pancreatic ß-cell function, and fat deposition support its administration to normal BMI patients with T2DM and visceral adiposity.

Comparison of analog insulin mix 50:50 with human insulin mix 30:70 in persons with type 2 diabetes during Ramadan.

AIM OF THE STUDY: To test if changing the Iftar insulin to a 50:50 mixed analog insulin from a 30:70 human insulin at the same total dose leads to improvement in the postprandial blood glucose (taken as after the main meal). Since the intermediate acting insulin dose is effectively lowered, the pre-Suhur blood glucose is also tested to see if this rises. METHODS: The Iftar human 30:70 mixed insulin is substituted for a 50:50 one using insulin lispro protamine suspension and 50% insulin lispro (Humalog® Mix50/50™), whilst maintaining the same total dose. The participants were also changed to 75% insulin lispro protamine suspension and 25% insulin lispro (Humalog® Mix75/25™) at the same pre-Ramadan dose for their Suhur injection (Experimental group). A similar number of controls continued their 30:70 mixed human insulin at the same dose during Ramadan (Control group). Pre-Ramadan and during Ramadan fasting and postprandial (3 hours) and pre-Suhur blood glucose (BG) are tested in 20 subjects and 20 controls by the patients using home glucose meters. Hypoglycaemia, defined as a BG of ≤ 70 mg%, was tested for by the patients and noted if they experience symptoms of it. Severe hypoglycaemia occurred if the patient needed assistance for recovery. No insulin dose adjustments are made in either group and any other anti-diabetic treatment was continued. Pre- and post-Ramadan HbA1 c and body weight are measured. The number of days fasted and baseline characteristics are age, gender, and duration of diabetes are also noted. Differences between groups in parameters were assessed using ANCOVA to adjust for pre-Ramadan values of age, gender, and duration of diabetes. RESULTS: All the participants fasted for at least 29 days. The 2 groups were not significantly different at baseline. During Ramadan, mean postprandial BG in the Experimental group was lower by 21.1 mg% (1.2 mmol/l) (95% CI 12.6, 29.7; P < 0.001). Similarly, after Ramadan mean HbA1 c in the Experimental group was lower by 0.4% (95% CI 0.1%, 0.8%; P = 0.01). No significant differences between the groups were detected in mean bodyweight after Ramadan (P = 0.86) or mean fasting BG during Ramadan (P = 0.07). There was no difference in incidence of hypoglycaemia. CONCLUSIONS: Switching from human insulin mix 30:70 to analog insulin mix 50:50 results in better post main meal control in Ramadan, without affecting HbA1c, or increasing the incidence of hypoglycaemia.

Similar glucose control with basal-bolus regimen of insulin detemir plus insulin aspart and thrice-daily biphasic insulin aspart 30 in insulin-naive patients with type 2 diabetes: Results of a 50-week randomized clinical trial of stepwise insulin intensification.

OBJECTIVE: This study aimed to demonstrate the non-inferiority of 50-week treatment with stepwise insulin intensification of basal-bolus insulin analogues [insulin detemir (IDet) and aspart (IAsp)] versus biphasic insulin aspart 30 (BIAsp30) in insulin-naive type 2 diabetes mellitus (T2DM) patients not controlled by oral glucose-lowering drugs (OGLDs). RESEARCH DESIGN AND METHODS: In this open-label multicentre, multinational, randomized, parallel-arm treat-to-target trial, 403 insulin-naive patients with T2DM in four African countries were randomized to either an IDet+IAsp (n = 200) or BIAsp1-2-3 (n = 203) treatment group. Stepwise insulin intensification was performed at the end of 14, 26 and 38 weeks, depending on HbA1c values. The primary endpoint was change in HbA1c after 50 weeks of treatment. Safety variables were hypoglycaemia incidence, occurrence of adverse events and weight gain. RESULTS: Non-inferiority of the IDet+IAsp versus BIAsp1-2-3 treatment regimen was demonstrated by their similar HbA1c levels at the end of trial (IDet+IAsp: baseline 8.6%, 50 weeks 7.4%; BIAsp1-2-3: baseline 8.7%, 50 weeks 7.3%; full analysis set difference: 0.1% [95% CI: -0.1, 0.3]; per protocol: 0.2% [95% CI: -0.1, 0.4]). At week 50, 40.3 and 44.9% of patients achieved HbA1c <7.0% with IDet+IAsp and BIAsp1-2-3, respectively. The rate of overall hypoglycaemia during the trial was also similar in both groups (IDet+IAsp: 9.4 events/patient-year; BIAsp1-2-3: 9.8 events/patient-year). CONCLUSION: Insulin initiation and intensification using IDet+IAsp was not inferior to BIAsp1-2-3 in insulin-naive patients with T2DM not controlled by OGLDs. Both regimens led to similar reductions in HbA1c values after 50 weeks of treatment.

Safety and efficacy of biphasic insulin aspart 30 in type 2 diabetes patients switched from either biphasic or basal human insulin: results from the Gulf cohort of the A1 chieve study.

AIM: The 24-week, international, non-interventional A1 chieve study aimed to evaluate the safety and efficacy of insulin analogues in type 2 diabetes (T2D) in different countries. This sub-analysis reports results for T2D patients who switched from either biphasic human insulin (BHI) or human neutral protamine Hagedorn (NPH) insulin to biphasic insulin aspart 30 (BIAsp 30) in the Gulf cohort. METHODS: Gulf patients with T2D who switched to BIAsp 30 from either BHI or NPH insulin were included. Safety and efficacy measurements were made by the physicians as part of routine clinical care. RESULTS: A total of 1486 patients switched from BHI to BIAsp 30 (BIP group) and 232 patients switched from NPH insulin to BIAsp 30 (NEU group). Baseline glycated haemoglobin A1c (HbA1c ) was poor in patients in the BIP and NEU groups (mean value ± SD: 9.4 ± 1.8% and 9.7 ± 1.5%, respectively). Significant reductions in the proportion of patients reporting hypoglycaemia (overall, major, minor and nocturnal) were noted in the BIP group after 24 weeks of BIAsp 30 therapy (p < 0.001). No major hypoglycaemic events were reported at Week 24 in the NEU group. In both groups, the mean HbA1c , fasting plasma glucose and postprandial plasma glucose improved significantly after 24 weeks of BIAsp 30 therapy (p < 0.001). The mean body weight, lipid parameters and systolic blood pressure also improved significantly in both groups (p < 0.05). CONCLUSION: BIAsp 30 therapy enhanced glycaemic control over 24 weeks and was well-tolerated in T2D patients poorly controlled on prestudy BHI or NPH insulin.

Ten years of experience with biphasic insulin aspart 30: from drug development to the latest clinical findings.

Biphasic insulin aspart 30 (BIAsp 30) includes 30% soluble rapid-acting insulin aspart (IAsp) along with an intermediate-acting 70% protaminated IAsp that provides coverage of prandial and basal insulin in a single injection. As BIAsp 30 has been available internationally for 10 years, this review provides a comprehensive overview of the discovery of BIAsp 30, its pharmacokinetic and pharmacodynamic profile, safety and efficacy outcomes from the clinical trial programme, 'real-life' clinical insights provided by observational study data, and cost effectiveness and quality-of-life information. These studies have demonstrated that BIAsp 30 once or twice daily is an appropriate option for insulin initiation. BIAsp 30 also provides a switch option in patients on biphasic human insulin (BHI). Switching from BHI to BIAsp 30 is associated with improved postprandial glucose (PPG) and reduced nocturnal and major hypoglycaemia, although daytime hypoglycaemia is higher with BIAsp 30. Intensification of BIAsp 30 can be achieved by increasing the number of daily doses up to three times daily with meals. Therefore, BIAsp 30 provides an intensification option for individuals who are not achieving control with basal insulin and would prefer the simplicity of a single biphasic insulin instead of progressing to a basal-bolus approach. BIAsp 30 has a simple dose-titration algorithm, which enables patients to effectively self-titrate their insulin dose. Cost-effectiveness analyses have demonstrated that BIAsp 30 is cost effective or dominant compared with BHI 30 or insulin glargine in a number of healthcare settings. In conclusion, BIAsp 30 offers a simple and flexible option for insulin initiation and intensification that provides coverage of both fasting and prandial glucose.

A comparison of pharmacokinetics and pharmacodynamics of insulin aspart, biphasic insulin aspart 70, biphasic insulin aspart 50, and human insulin: a randomized, quadruple crossover study.

BACKGROUND: We compared the pharmacokinetic and pharmacodynamic profiles of insulin aspart, biphasic insulin aspart 70 (BIAsp70) and 50 (BIAsp50) (containing 70% and 50% rapid-acting insulin aspart, respectively), and soluble human insulin under experimental conditions. SUBJECTS AND METHODS: In this randomized, four-period crossover study, 19 type 1 diabetes patients received subcutaneous injections of identical doses (0.2 U/kg) of insulin aspart, BIAsp70, or BIAsp50 immediately before a standardized meal or human insulin 30 min before meal. Plasma glucose and serum insulin were measured for 12 h postprandially. RESULTS: The pharmacokinetic and pharmacodynamic profiles of human insulin differed from those of insulin aspart, BIAsp70, and BIAsp50. The three different aspart preparations had easily distinguishable features with regard to onset and duration of action. Insulin aspart preparations were, on average, absorbed twice as fast as human insulin. In the initial phases (0-4 h and 0-6 h), the insulin area under the concentration-time curve (AUC(ins)) was significantly higher during insulin aspart treatment compared with the others, whereas insulin aspart had a significantly lower AUC(ins) over the last 6 h (P<0.05). BIAsp70 and BIAsp50 provided insulin coverage comparable to that of human insulin over the last 6 h. Insulin aspart had the most pronounced onset of action and the shortest duration. Comparing with insulin aspart and BIAsp70, BIAsp50 revealed a closer treatment ratio to human insulin on pharmacodynamic end points. CONCLUSIONS: BIAsp70 and BIAsp50 injected immediately before a meal are at least as effective as human insulin injected 30 min earlier in controlling postprandial glycemic excursions. BIAsp50 showed the greatest similarity to human insulin with regard to pharmacokinetic and pharmacodynamic profiles.