Safety and effectiveness of biphasic insulin aspart 30/70 (NovoMix ® 30) when switching from human premix insulin in patients with type 2 diabetes: subgroup analysis from the 6-month IMPROVE™ observational study (original) (raw)
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… journal of clinical …, 2009
Aims:IMPROVE™ is an open-label, multinational, non-randomised, 26-week observational study designed to evaluate the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in routine clinical practice. Here, we report data for patients switching to BIAsp 30 from human premixed insulin.Methods:Patients (n=3856) with type 2 diabetes previously receiving human premixed insulin with or without oral antidiabetic drugs were eligible for inclusion. Demographic data, efficacy end-points (HbA1c, fasting blood glucose and postprandial blood glucose) and safety end-points (serious adverse drug reactions, hypoglycaemia and adverse events) were collected at baseline and final visit. A subgroup analysis of mean dose change was also undertaken.Results:Switching patients to BIAsp 30 resulted in significant improvements in glycaemic control combined with a reduced risk of hypoglycaemia. Patients who reached the HbA1c target (< 7%) had shorter diabetes duration, lower HbA1c at baseline and needed less insulin. Over 30% of patients were able to reach this target without experiencing hypoglycaemia over the 26-week period. Compared with asymmetric dose switching, unit-for-unit switching resulted in the highest proportion of patients reaching HbA1c target and incurred the least amount of dose titration.Conclusions:A unit-for-unit switch is the most effective as well as the simplest approach when transferring patients from biphasic human insulin 30 to BIAsp 30.
International Journal of Clinical Practice, 2009
Aims: The IMPROVE™ observational study evaluated the safety profile and effectiveness of biphasic insulin aspart 30/70 (BIAsp 30) in patients with type 2 diabetes in routine practice in 11 countries.Methods: Patients who initiated insulin therapy with, or switched existing insulin therapy to, BIAsp 30 in routine care were eligible for this 26-week, non-interventional observational study. Data on adverse events, hypoglycaemia and glycaemic parameters were obtained from patients’ diaries and medical notes. Questionnaire-based patient treatment satisfaction was also measured. We report global results and, uniquely for a diabetes observational study, country-specific data.Results: A total of 52,419 patients were enrolled from three prestudy treatment groups: no pharmaceutical therapy (n = 8966, diabetes duration 2.0 years, baseline HbA1c 9.9%), oral antidiabetic drugs (OADs) only (n = 33,797, diabetes duration 7.4 years, baseline HbA1c 9.2%) and insulin ± OADs (n = 9568, diabetes duration 10.4 years, baseline HbA1c 9.3%). At final visit, HbA1c, fasting and postprandial blood glucose were significantly reduced from baseline in all subgroups (no pharmaceutical therapy: −3.1%, −5.9 and −9.0 mmol/l, respectively; OADs-only: −2.1%, −4.1 and −6.1 mmol/l; insulin ± OADs: −2.0%, −3.3 and −5.1 mmol/l). Major hypoglycaemia rates decreased in all subgroups; minor hypoglycaemia increased in the insulin-naïve groups. There was no mean weight gain across subgroups. Across all countries, glycaemic parameters and major hypoglycaemia were reduced; weight increases were seen in some countries. Treatment satisfaction increased in all subgroups and countries following BIAsp 30 therapy.Conclusions: Initiating insulin with, or switching insulin therapy to, BIAsp 30 in routine care resulted in improved glycaemic control, reduced major hypoglycaemia and greater treatment satisfaction.
Diabetes, Obesity and Metabolism, 2009
Aim: To evaluate clinical efficacy and safety of biphasic insulin aspart (BIAsp) 30 twice daily (b.i.d.) vs. BIAsp 50 or BIAsp 70 (high-mix regimens) thrice daily (t.i.d.) all in combination with metformin in a 36-week clinical trial in subjects with type 2 diabetes. Methods: Efficacy measurements included haemoglobin A 1c (HbA 1c ) and eight-point plasma glucose (PG); safety included adverse events (AEs) and hypoglycaemic episodes. The three treatment groups (approximately 200 subjects in each group) were well matched regarding sex ratio, ethnicity, age and body mass index. Results: After 12 weeks, 43% and 54% in the BIAsp 50 and 70 groups, respectively, switched their dinner insulin to BIAsp 30. Both high-mix regimens were non-inferior to BIAsp 30 b.i.d., as measured by change in HbA 1c , and the BIAsp %50 regimen was superior. The odds for meeting the American Diabetes Association and The American Association of Clinícal Endocrinologist HbA 1c targets of <7% and 6.5%, respectively, were significantly higher with the BIAsp 50 regimen than with BIAsp 30. A significantly lower PG level was achieved from lunch until 02:00 hours with both high-mix regimens compared with BIAsp 30 b.i.d. AEs were mild or moderate with all three regimens. Frequency of hypoglycaemic episodes was comparable for the BIAsp 50 and the BIAsp 30 b.i.d. regimens but was significantly higher with BIAsp 70 t.i.d. Conclusions: Glycaemic control improved with BIAsp 50 t.i.d. without higher incidence of hypoglycaemia compared with BIAsp 30 b.i.d.; with BIAsp 70 t.i.d. lower PG levels from lunch to 02.00 hours, but more hypoglycaemic episodes were obtained compared with BIAsp 30 b.i.d. (Clinical Trials.gov ID no: NCT00184574).
Clinical Therapeutics, 2002
The purpose of this study was to compare the pharmacokinetics and pharmacodynamics of the premixed insulin analogue biphasic insulin aspart (BIAsp 30) with the equivalent premixed biphasic human insulin (BHI 30), administered twice daily, in patients with type 2 diabetes mellitus. In this randomized, double-blind, crossover trial, 13 patients (mean age, 64 years; baseline mean glycosylated hemoglobin, 7.7%; mean body mass index, 28.1 kg/m2) received 2 weeks of treatment with BIAsp 30 and 2 weeks of BHI 30 administered immediately before dinner and breakfast. At the end of each 2-week treatment period, 24-hour serum insulin and glucose profiles were determined using specific 2-sided enzyme-linked immunosorbent assays. All pharmacodynamic and pharmacokinetic end points were analyzed using analysis of variance. Total daily insulin exposure was similar between treatment periods. Mean area under the total insulin concentration-time profile during the 2 hours following administration of BIAsp 30 was 17% greater than that of BHI 30 after dinner and 44% greater after breakfast; both differences were statistically significant. The maximum serum insulin aspart concentrations following BIAsp 30 were significantly higher after dinner (18%) and breakfast (35%). Peak serum insulin concentration was reached 1 hour earlier after breakfast and 45 minutes earlier after dinner in the BIAsp 30 group; differences were significant only after breakfast. The mean daily prandial glucose excursion was significantly lower for BIAsp 30 (16.2 mmol x h x L(-1)) than BHI 30 (17.9 mmol x h x L(-1)). Postprandial 4-hour glucose excursions were significantly lower with BIAsp 30 than with BHI 30 after dinner and breakfast, but were significantly greater after lunch. Mean 24-hour and nocturnal serum glucose concentrations were similar, and both insulins were associated with &amp;amp;amp;amp;amp;amp;amp;lt; or = 7 minor and no major hypoglycemic events. Premeal injection of BIAsp 30 in a twice-daily regimen significantly reduced overall postprandial glucose excursions. This effect may be of importance when improvement in postprandial glucose control is desired.
Diabetes Research and Clinical Practice, 2012
Aims: Assess safety and glycaemic control in patients initiating insulin with, or switching from basal insulin to, biphasic insulin aspart 30/70 (BIAsp 30) in primary care in Finland. Methods: A non-randomised, non-interventional, open-label, 26-week study of type 2 diabetes (T2D) patients prescribed BIAsp 30 by their physician, who determined starting dose, titration and injection frequency. Results: 496 patients provided safety data (insulin-naïve n = 197; prior insulin n = 299 [84.9% received NPH insulin]). Three patients (0.6%) reported four SADRs (three hypoglycaemia, one hypoglycaemia with unconsciousness). HbA1c was significantly (p < 0.0001) reduced after 26 weeks' BIAsp 30 therapy (final dose): insulin-naïve À1.4% (44.4 IU); prior insulin À1.1% (77.4 IU). HbA1c < 7.0% was achieved by 10% of insulin-naïve patients at baseline and 51% at 26-week follow-up. In the prior insulin group, 7% and 30% of patients had HbA1c < 7.0% at baseline and 26 weeks, respectively. Minor hypoglycaemia increased significantly from baseline to study end: insulin-naïve 0.66-6.45 events/patient/year (p < 0.0001); prior insulin 5.11-8.58 events/patient/year (p < 0.05). Weight increased by 1.0 kg (insulin-naïve) and 1.3 kg (previous insulin). Conclusion: BIAsp 30, initiated and titrated in T2D patients in primary care in Finland, showed a good safety profile and significantly improved glycaemic control.
Long-term efficacy and safety of biphasic insulin aspart in patients with type 2 diabetes
European Journal of Internal Medicine, 2004
Background: In this study, we sought to compare the long-term safety and efficacy of biphasic insulin aspart 30 (BIAsp30) with that of biphasic human insulin 30 (BHI30) over a period of 24 months in patients with type 2 diabetes. Methods: Patients with type 2 diabetes (n=125) were assigned to twice-daily BIAsp30 or BHI30 and participated in both a 3-month initial period and a 21-month extension of a randomized, controlled, multinational trial. Results: No significant difference was found in mean HbA 1c after 24 months [BIAsp30, 8.35F0.20%; BHI30 8.13F0.16%; adjusted mean difference (BIAsp30ÀBHI30) 0.03 (90% CI À0.29 to 0.34)%, P=0.89]. The proportion of patients experiencing major hypoglycaemia was also similar during the first year (BIAsp30, 5%; BHI30, 8%; P=0.72), but it was significantly lower with BIAsp30 than with BHI30 during the second year (BIAsp30, 0%; BHI30, 10%; P=0.04). The proportion experiencing minor hypoglycaemia was not significantly different. No significant difference was recorded in changes in nonspecific insulin antibody levels after 24 months (BIAsp30, 4.87F1.92%; BHI30; 1.00F1.66%; P=0.13). Body weight change was 0.05F0.81 kg in the BIAsp30 group and 2.00F0.69 kg in the BHI30 group ( P=0.07). Conclusions: Reduced major hypoglycaemia compared with BHI30 during the second year of treatment and comparable HbA 1c levels after 24 months appear to support the hypothesis that the improved pharmacokinetic profile of BIAsp30 may favourably affect the balance between hypoglycaemia and hyperglycaemia in insulin-treated type 2 diabetes. D
Use of Biphasic Insulin Aspart 30 in Type 2 Diabetes Treatment: Expert Panel Recommendations
The Turkish Journal of Endocrinology and Metabolism
The goals of Type 2 diabetes treatment are to eliminate the hyperglycemia resulting from insulin insufficiency and/or insulin resistance, delay beta cell damage/depletion, and prevent other metabolic co-morbidities and complications. In the current treatment algorithms, lifestyle changes (medical nutrition therapy, physical exercise) and oral anti-diabetics are followed by insulin therapy, which is considered a replacement therapy for Type 2 diabetes. Pre-mixed insulin preparations, which are an option for patients with poor blood glucose level control under oral anti-diabetics treatment, have been developed to meet both basal and prandial insulin needs by simulating the physiological changes in insulin levels. The consensus on the necessity of individualizing insulin therapy requires physicians to have a detailed knowledge of the various uses of insulin. Therefore, this comprehensive consensus statement has been prepared by a panel of expert endocrinologists from different regions of Turkey to help physicians use biphasic insulin aspart 30 in suitable patients at the right time. In this statement, expert panel opinions on (a) Recommendations for the appropriate initiation, titration, and intensification of insulin treatment, and (b) The treatment algorithms in initiation, titration, and intensification of biphasic insulin aspart 30 treatment and special conditions specific to changing treatment regimen are presented.
International Journal of Clinical Practice, 2009
Aims: The international IMPROVE™ observational study investigated the safety profile and effectiveness of biphasic insulin aspart 30/70 (BIAsp 30) in the routine treatment of patients with type 2 diabetes. We present analyses for the subgroup of patients who switched from basal insulin to BIAsp 30.Methods: Patients in routine care who started insulin therapy with or switched to BIAsp 30 from existing insulin regimens were eligible for this 26-week study. This analysis includes only patients previously treated with basal insulin. Outcomes including adverse events, hypoglycaemic events and glycaemic profile were recorded from patients’ notes, recall and diaries.Results: Of the 748 patients included (age 59.7 ± 11.8 years, diabetes duration 11.4 ± 7.3 years, baseline HbA1c 9.1 ± 1.6%), 497 were previously using human neutral protamine Hagedorn (NPH) insulin and 245 analogue basal insulin. Overall, major and minor hypoglycaemia rates decreased from baseline to final visit (major: 0.171 to 0.011; minor: 9.70 to 5.89 events/patient-year) and were similar between the subgroups. HbA1c and fasting blood glucose were significantly reduced from baseline (NPH prestudy: −1.6%, −2.4 mmol/l; analogue basal prestudy: −1.8%, −2.4 mmol/l), as was postprandial blood glucose, with 33.8% of patients achieving the HbA1c target < 7% without hypoglycaemia. Insulin dose increased slightly from prestudy (0.33 ± 0.21 U/kg), baseline (0.40 ± 0.20 U/kg) to final visit (0.52 ± 0.26 U/kg); most patients (76%) followed a twice-daily regimen at final visit. Body weight did not change significantly and treatment satisfaction increased.Conclusions: Patients with type 2 diabetes inadequately controlled on basal insulins may improve their glycaemic control by intensification to BIAsp 30 therapy.
The Review of Diabetic Studies, 2008
OBJECTIVE: To investigate tolerability and glycemic control over 26 weeks in patients with type 2 diabetes (T2D) who initiated insulin with, or switched to, biphasic insulin aspart 30/70 (BIAsp 30) in routine clinical care. METH-ODS: This was a non-randomized, non-interventional, open-label, observational study involving patients under the care of approximately 150 insulin-prescribing physicians in Denmark. All patients enrolled were prescribed BIAsp 30 in routine care. Starting dose, dose titration and injection frequency were determined individually by each physician. Information on serious adverse drug reactions (SADR), glycemic parameters and hypoglycemic events were obtained from patients' notes, patients' diaries and recall, and transferred to case report forms by physicians at baseline (during 4 weeks prior to BIAsp 30 therapy) and after 12 and 26 weeks of treatment. RESULTS: 421 subjects were recruited and 392 provided safety data. The age (mean ± SD) was 62.0 ± 11.4 years, body mass index (BMI) 30.4 ± 6.4 kg/m 2 , duration of diabetes 9.1 ± 8.1 years and HbA1c (%) 9.4 ± 1.7. 199 subjects were prior insulin users and 193 were insulinnaïve patients. Four patients reported a SADR (3 hypoglycemia, 1 severe hypoglycemia). HbA1c was significantly reduced after 26 weeks of BIAsp 30 therapy: prior insulin users -1.2%, insulin-naïve patients -2.2% (both p < 0.001). 28% and 41% of patients, respectively, reached target HbA1c < 7%. Overall the hypoglycemia rate was lower for insulin-naïve patients than for prior insulin users: 5.0 vs. 6.6 episodes/patient-year (p < 0.05). CONCLUSION: Initiating insulin with, or switching insulin to, BIAsp 30 in routine care was safe and effective in patients with T2D.