Biphasic insulin aspart 30 in the treatment of elderly patients with type 2 diabetes: a subgroup analysis of the PRESENT Korea NovoMixstudy.

AIMS: To evaluate the efficacy, safety and treatment satisfaction with biphasic insulin aspart 30 (BIAsp30) in elderly patients with type 2 diabetes. METHODS: The Physicians' Routine Evaluation of Safety and Efficacy of NovoMix 0 Therapy Korea study was a 6-month, prospective, observational study. No study-specific interventions were involved except the collection of data. All patients with type 2 diabetes not adequately controlled on their previous therapy, and who were prescribed BIAsp30 as monotherapy, or in combination with oral hypoglycaemic agents, were eligible for the study. This subgroup analysis was based on the outcomes in patients > or years (n = 1720). RESULTS: BIAsp30 treatment was associated with significant mean reductions in haemoglobin A1c, fasting plasma glucose and post-prandial plasma glucose levels of 1.2 +/- 1.6%, 2.3 +/- 3.5 mmol/l and 4.8 +/- 5.3 mmol/l at 6 months (p < 0.0001 for all), from baseline levels of 9.1 +/- 1.7%, 10.7 +/- 3.4 mmol/l and 16.7 +/- 5.0 mmol/l, respectively. The rate of hypoglycaemia declined from 3.02 to 1.31 episodes per patient year, between baseline and study end. The proportion of patients reporting adverse drug reactions was low (0.3 and 0.1% at 3 and 6 months, respectively). Body weight gain was mild at <0.1 kg at 3 months, and 0.3 kg at 6 months. As compared to the previous treatment, >80% of patients were rated as being either 'very satisfied' or 'satisfied' with BIAsp30 treatment. CONCLUSIONS: In this subanalysis of Korean elderly patients with type 2 diabetes inadequately controlled on their previous therapies, treatment with BIAsp30 offered improvements in glycaemic control and was well tolerated. Body weight gain was minimal with BIAsp30, and treatment satisfaction among these patients appeared to be high.

Biphasic insulin aspart 30 treatment improves glycaemic control in patients with type 2 diabetes in a clinical practice setting: Chinese PRESENT study.

AIM: PRESENT (Physicians' Routine Evaluation of Safety and Efficacy of NovoMix 30 Therapy) is the largest, multinational, open-labelled, uncontrolled and completed observational study of the efficacy and safety of biphasic insulin aspart 30 (BIAsp 30) treatment in clinical practice. We present results of 3 months of treatment in Chinese patients with type 2 diabetes mellitus who were inadequately controlled on current treatment. METHODS: Patients received BIAsp 30 treatment with or without oral antidiabetic drugs (OADs). Patients were categorized according to their treatment prior to entering the study: drug-naive (n = 3697), OAD (n = 4754), insulin (n = 2392) or OAD + insulin (n = 817). RESULTS: At 3 months, significant reductions from baseline were observed in the mean haemoglobin A(1c) (HbA(1c)) (-2.24 +/- 1.67, -2.04 +/- 1.57, -1.82 +/- 1.49 and -1.86 +/- 1.61%), fasting plasma glucose (-3.93 +/- 3.12, -3.51 +/- 2.55, -2.99 +/- 2.93 and -3.38 +/- 3.16 mmol/l) and postprandial plasma glucose (-7.09 +/- 4.92, -6.51 +/- 4.02, -5.20 +/- 4.31 and -5.50 +/- 4.32 mmol/l) in the drug-naive, OAD, insulin and insulin + OAD groups respectively (p < 0.001). The proportions of patients in each group achieving target HbA(1c) of less than 7% were higher at 3 months (49.5, 51.8, 51.0 and 48.3%) compared with baseline (3.2, 4.2, 7.1 and 8.3%). The rates of hypoglycaemic episodes (events per patient-year) were lower at the end of the study in all the groups compared with baseline. Hypoglycaemic episodes were mostly minor and diurnal in nature. A total of 151 adverse drug reactions were reported, of which five were serious adverse drug reaction (SADRs). These SADRs were all symptoms of local hypersensitivity. CONCLUSIONS: The use of BIAsp 30 monotherapy or in combination with OADs in clinical practice was efficacious and safe in Chinese patients with poorly controlled type 2 diabetes.

Biphasic insulin aspart 30 treatment in patients with type 2 diabetes poorly controlled on prior diabetes treatment: results from the PRESENT study.

AIM: The safety and efficacy of biphasic insulin aspart (BIAsp30) were evaluated in patients uncontrolled on previous treatment (human insulin +/- oral hypoglycaemic agent [OHA] or OHA only) in routine clinical practice. METHODS: This was a large, multi-national, multicentre, prospective, 6-month study in type 2 diabetes mellitus patients who were prescribed BIAsp30. Changes in glycated haemoglobin (HbA(1c)), fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), proportion who achieved target HbA(1c) < 7% and rate of hypoglycaemic episodes were assessed. This paper evaluates outcomes in patients by diabetes duration (< 5, 5-10, 10-20 or >/= 20 years) stratified by prior therapy. RESULTS: After 6 months of treatment, glycaemia improved significantly across the duration subgroups. The improvement was better in insulin-naïve group versus prior insulin group: HbA(1c) decreased approximately 2.2%-points versus approximately 1.6%-points, FPG decreased approximately 4.5 mmol/L versus approximately 2.9 mmol/L and PPPG decreased approximately 6.8 mmol/L versus approximately 5.0 mmol/L. Target HbA(1c) was achieved by about one in four patients although insulin-naïve patients achieved this at comparatively lower BIAsp30 dose. Body weight remained relatively unchanged. Hypoglycaemic episodes appeared to be more frequent in the prior insulin group which decreased during the treatment period. CONCLUSIONS: According to this observational study, in clinical practice, initiating or transferring uncontrolled patients to biphasic insulin aspart improved glycaemic control without using a strict insulin algorithm.

Efficacy, safety and acceptability of biphasic insulin aspart 30 in Indian patients with type 2 diabetes: results from the PRESENT study.

AIM: The Physicians' Routine Evaluation of Safety and Efficacy of NovoMix 30 Therapy (PRESENT) study was done to assess the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in patients with type 2 diabetes mellitus in routine clinical practice. MATERIALS AND METHODS: This was a prospective, multicentric, multinational, observational study in type 2 diabetes patients. The patients were transferred to BIAsp 30 with or without oral antidiabetic drugs (OADs). We present the results of 6 months of treatment in the Indian cohort (n = 3559) with type 2 diabetes mellitus who were inadequately controlled on current treatment. RESULTS: At three and six months, significant reductions from baseline were observed in the mean glycated haemoglobin (HbA1c) (-1.32% and -1.94%), fasting plasma glucose (-56.16 mg/dl and -75.24 mg/dl) and post-prandial plasma glucose (-88.74 mg/dl and -119.16 mg/dl) (p < 0.001). A significantly greater proportion of patients achieved target HbAlc of less than 7% at six months (31.1%), compared with baseline (3.1%), of which 70.4% did not report hypoglycaemia. The rate of total hypoglycaemia was reduced from 3.1 events per patient-year at baseline to 1.5 events per patient-year at end of the study. Episodes were mostly minor and diurnal. Except for two serious adverse drug reactions (ADRs) reported by one patient at 3 months, there were no reports of ADRs during the treatment period. More than 95% of patients and doctors were "very satisfied" or "satisfied" with BIAsp 30 treatment, compared to previous treatment. CONCLUSIONS: The use of BIAsp 30 monotherapy or in combination with OADs in clinical practice was effective and safe in poorly controlled Indian type 2 diabetes patients. Both patients and doctors showed a high degree of treatment satisfaction.

Adding biphasic insulin aspart 30 once or twice daily is more efficacious than optimizing oral antidiabetic treatment in patients with type 2 diabetes.

AIM: To evaluate the efficacy and safety of adding biphasic insulin aspart 30 (BIAsp30; NovoMix 30) to existing oral antidiabetic agents (OADs) vs. optimizing OADs in a subgroup of Western Pacific patients with type 2 diabetes inadequately controlled on oral monotherapy or oral combination therapy. METHODS: This 26-week, multi-centre, open-labelled, randomized, two-arm parallel trial consisted of a 2-week screening period, followed by 24 weeks of treatment. Subjects randomized to BIAsp30 treatment (n = 129) received BIAsp30 once daily (o.d.) at dinnertime between Week 2 and Week 14, and those not reaching treatment targets were switched to twice daily (b.i.d.) BIAsp30 at Week 14 (n = 50). Subjects randomized to the OAD-only arm (n = 63) continued with their previous OAD treatment and, in an attempt to reach treatment goals, the dose was optimized (but OAD unchanged) in accordance to local treatment practice and labelling. RESULTS: Significantly greater reductions in HbA(1c) over Weeks 0-13 with BIAsp30 (o.d.) vs. OAD-only treatment (1.16 vs. 0.58%; p < 0.001), and over Weeks 0-26, with BIAsp30 (o.d.) and BIAsp30 (b.i.d.) treatments vs. OAD-only treatment (1.24 vs. 1.34 vs. 0.67%; p < 0.01). Hypoglycaemic episodes were reported in 54% of the patients in BIAsp30 (o.d. and b.i.d. pooled) and 30% of the patients in OAD-only group. All episodes were minor or symptomatic, except for one in each treatment group, which was major. CONCLUSIONS: Initiating BIAsp30 treatment is a safe and more effective way to improve glycaemic control in Western Pacific patients with type 2 diabetes inadequately controlled with oral monotherapy or oral combination therapy compared with optimizing oral combination therapy alone. In patients not reaching treatment target on BIAsp30 (o.d.), treatment with BIAsp30 (b.i.d.) should be considered.

Twice daily biphasic insulin aspart improves postprandial glycaemic control more effectively than twice daily NPH insulin, with low risk of hypoglycaemia, in patients with type 2 diabetes.

OBJECTIVE: Biphasic insulin aspart 30 (BIAsp30) is a dual release formulation, containing 30% soluble and 70% protamine-crystallized insulin aspart. This study compared the glycaemic control and safety profiles achieved with either twice daily BIAsp30 or NPH insulin in patients with type 2 diabetes not optimally controlled by oral hypoglycaemic agents (OHAs), NPH insulin or a combination of both. METHODS: In this 16-week multinational, parallel-group, double-blind trial, 403 such patients were randomized to receive either BIAsp30 or NPH insulin immediately before breakfast and evening meals. OHAs were discontinued at randomization. Efficacy was assessed by glycosylated haemoglobin (HbA1c) and self-recorded daily 8-point blood glucose (BG) profiles. Hypoglycaemic and other adverse events were the chosen safety parameters. RESULTS: HbA1c concentration decreased by >0.6% (p < 0.0001 vs. baseline) in both groups, with metabolic control continuing to improve throughout the trial without reaching a stable level. Patients who switched from once or twice daily NPH monotherapy to twice daily BIAsp30 achieved a significantly greater reduction in HbA1c (0.78%) than those randomized to twice daily NPH insulin (0.58%; p = 0.03). BIAsp30 decreased mean daily postprandial glycaemic exposure to a greater extent than NPH insulin (mean difference = 0.69 mmol/l; p < 0.0001), reflecting greater decreases in the postbreakfast and postdinner increments (of 1.26 and 1.33 mmol/l, respectively), although postlunch increment was relatively increased (by 0.56 mmol/l). Despite the greater reduction in overall postprandial glycaemic exposure in the BIAsp30 group, the overall safety profile of BIAsp30 was equivalent to that of NPH insulin with <2% of patients experiencing major hypoglycaemia, and approximately 33% reporting minor hypoglycaemic episodes, in both groups. CONCLUSION: Twice daily BIAsp30 reduced postprandial glucose exposure to a significantly greater extent than NPH insulin and was at least as effective at reducing HbA1c in patients with type 2 diabetes. Both insulins were well tolerated. In patients poorly controlled on OHAs or NPH alone, glycaemic control can be improved by switching to twice daily BIAsp30, without increasing hypoglycaemic risk.

Comparative bioequivalence study of rifampicin and isoniazid combinations in healthy volunteers.

OBJECTIVE: To assess the bioavailability of rifampicin (RMP) in three brands of combination formulations of anti-tuberculosis drugs. DESIGN: A three-way double-blind, cross-over bioavailability study of RMP and isoniazid (INH), consisting of a comparison of a two-drug combination of tablets of RMP and INH each separately (reference brand R) and a tablet of RMP + INH (brand N), and a capsule of RMP + INH (brand L) was carried out in 12 healthy male volunteers. Coded plasma samples were analysed for levels of RMP as well as INH and acetylisoniazid (ACINH) by two high performance liquid chromatography (HPLC) methods. RESULTS: The mean values of RMP in brand N (Cmax 6.49+/-0.52 microg/mL, Tmax 2.33+/-0.18 h, AUC(0-24h) 39.83+/-3.44 microg/mL.h) were comparable with those obtained with brand R (Cmax 5.22+/-0.59 microg/mL, Tmax 2.50+/-0.12 h, AUC(0-24h) 33.33+/-3.47 microg/mL.h). The mean values of RMP in brand L (Cmax 3.05+/-0.52 microg/ mL, Tmax 3.79+/-0.57 h and AUC(0-24h) 21.78+/-3.67 microg/ mL.h) were significantly different from those in brand R. Nevertheless, all of the pharmacokinetic parameters obtained for INH and ACINH in all three brands were comparable. CONCLUSION: Using brand R as a comparison, brand N was bioequivalent and brand L was not bioequivalent.

Clinical relevance of reduced bioavailability of rifampicin.

Bioavailability (BA) of rifampicin (RMP) is a critical factor in successful treatment of tuberculosis. The BA of RMP can be reduced by pharmaceutical factors, patient factors and drug interactions. Failure of treatment and development of drug resistance are potential consequences of reduction in BA and it is necessary to understand and control the factors influencing BA of RMP.