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Cost Effectiveness and Resource... Oct 2011Compared to conventional human basal insulin (neutral protamine Hagedorn; NPH) the long-acting analogue insulin glargine (GLA) is associated with a number of advantages...
BACKGROUND
Compared to conventional human basal insulin (neutral protamine Hagedorn; NPH) the long-acting analogue insulin glargine (GLA) is associated with a number of advantages regarding metabolic control, hypoglycaemic events and convenience. However, the unit costs of GLA exceed those of NPH. This study aims to systematically review the economic evidence comparing GLA with NPH in basal-bolus treatment (intensified conventional therapy; ICT) of type 1 diabetes in order to facilitate informed decision making in clinical practice and health policy.
METHODS
A systematic literature search was performed for the period of January 1st 2000 to December 1st 2009 via Embase, Medline, the Cochrane Library, the databases GMS (German Medical Science) and DAHTA (Deutsche Agentur für Health Technology Assessment), and the abstract books of relevant international scientific congresses. Retrieved studies were reviewed based on predefined inclusion criteria, methodological and quality aspects. In order to allow comparison between studies, currencies were converted using purchasing power parities (PPP).
RESULTS
A total of 7 health economic evaluations from 4 different countries fulfilled the predefined criteria: 6 modelling studies, all of them cost-utility analyses, and one claims data analysis with a cost-minimisation design. One cost-utility analysis showed dominance of GLA over NPH. The other 5 cost-utility analyses resulted in additional costs per quality adjusted life year (QALY) gained for GLA, ranging from € 3,859 to € 57,002 (incremental cost effectiveness ratio; ICER). The cost-minimisation analysis revealed lower annual diabetes-specific costs in favour of NPH from the perspective of the German Statutory Health Insurance (SHI).
CONCLUSIONS
The incremental cost-utility-ratios (ICER) show favourable values for GLA with considerable variation. If a willingness-to-pay threshold of £ 30,000 (National Institute of Clinical Excellence, UK) is adopted, GLA is cost-effective in 4 of 6 cost utility analyses (CUA) included. Thus insulin glargine (GLA) seems to offer good value for money. Comparability between studies is limited because of methodological and country specific aspects. The results of this review underline that evaluation of insulin therapy should use evidence on efficacy of therapy from information synthesis. The concept of relating utility decrements to fear of hypoglycaemia is a plausible approach but needs further investigation. Also future evaluations of basal-bolus insulin therapy should include costs of consumables such as needles for insulin injection as well as test strips and lancets for blood glucose self monitoring.
PubMed: 21978524
DOI: 10.1186/1478-7547-9-15 -
Expert Review of Pharmacoeconomics &... Dec 2011The prevalence of diabetes and cost of associated treatment are steadily increasing, as is the resulting burden on healthcare systems worldwide. Current treatment... (Review)
Review
The prevalence of diabetes and cost of associated treatment are steadily increasing, as is the resulting burden on healthcare systems worldwide. Current treatment recommendations for Type 1 and Type 2 diabetes advise a prominent role for basal insulin. We examined the published health-economic literature pertaining to the basal insulin analog insulin detemir (IDet) to determine whether IDet is a cost-saving and/or cost-effective treatment for suboptimally controlled Type 1 or Type 2 diabetes. A total of 15 modeling studies were assessed, most of which found IDet to be cost effective compared with neutral protamine Hagedorn and as cost effective as insulin glargine. Those that did not find IDet to be cost effective set the disutility of hypoglycemic events to almost zero or assumed a higher dose of IDet with no difference in treatment effect, ignoring the clinical benefits and cost savings associated with IDet in studies demonstrating comparable or superior glycemic control with less hypoglycemia versus other basal insulins. The evidence suggests that IDet is cost effective versus neutral protamine Hagedorn and at least as cost effective as insulin glargine in the treatment of patients with suboptimally controlled Type 1 and Type 2 diabetes.
Topics: Blood Glucose; Cost Savings; Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Costs; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Models, Economic; Quality-Adjusted Life Years; Time Factors; Treatment Outcome
PubMed: 21961796
DOI: 10.1586/erp.11.73 -
Polskie Archiwum Medycyny Wewnetrznej 2011Although numerous studies showed an improvement in glycemic control in type 1 diabetic patients treated with long-acting insulin analogue detemir compared with Neutral... (Comparative Study)
Comparative Study Meta-Analysis Review
INTRODUCTION
Although numerous studies showed an improvement in glycemic control in type 1 diabetic patients treated with long-acting insulin analogue detemir compared with Neutral Protamine Hagedorn (NPH) insulin, the beneficial effects of insulin detemir has not been confirmed by all investigators.
OBJECTIVES
The aim of the study was to compare the effect of treatment with detemir insulin vs. NPH insulin on metabolic control, hypoglycemic episodes, and body weight gain in patients with type 1 diabetes by means of a systematic review and a meta-analysis.
METHODS
The following electronic databases were searched up to November 2010: MEDLINE, EMBASE, and the Cochrane Library. Additional references were obtained from the reviewed articles. Only randomized controlled trials of at least 12-week duration with basal-bolus regimen therapies using detemir insulin vs. NPH insulin were included.
RESULTS
The analysis included 10 studies involving 3825 patients with type 1 diabetes. Combined data from all trials showed a statistically significant reduction in hemoglobin A1c (HbA1c) (weighted mean difference: [WMD] -0.073, 95% CI -0.135 to -0.011, P = 0.021) in the detemir group compared with the NPH group. There was also a significant reduction of fasting plasma glucose (FPG) (WMD - 0.977 mmol/l, 95% CI -1.395 to -0.558, P <0.001), all-day hypoglycemic episodes (relative risk [RR] 0.978, 95% CI 0.961-0.996), severe hypoglycemic episodes (RR 0.665, 95% CI 0.547-0.810), nocturnal hypoglycemic episodes (RR 0.877, 95% CI 0.816-0.942), as well as smaller body weight gain (WMD -0.779 kg, 95% CI -0.992 to -0.567) in patients using detemir insulin compared with those using NPH insulin.
CONCLUSIONS
Basal-bolus treatment with insulin detemir, as compared with NPH insulin, provided a minor benefit in terms of the HbA1c value and significantly reduced FPG in type 1 diabetic patients. Treatment with detemir insulin was also superior to NPH insulin in reducing the risk of all-day, nocturnal, and severe hypoglycemic episodes, with the added benefit of reduced weight gain.
Topics: Blood Glucose; Body Weight; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Drug Administration Schedule; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin, Long-Acting; Randomized Controlled Trials as Topic
PubMed: 21878861
DOI: No ID Found -
Health Technology Assessment... Jul 2010In May 2008, the National Institute for Health and Clinical Excellence (NICE) issued an updated guideline [clinical guideline (CG) 66] for the management of all aspects... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In May 2008, the National Institute for Health and Clinical Excellence (NICE) issued an updated guideline [clinical guideline (CG) 66] for the management of all aspects of type 2 diabetes. This report aims to provide information on new drug developments to support a 'new drugs update' to the 2008 guideline.
OBJECTIVE
To review the newer agents available for blood glucose control in type 2 diabetes from four classes: the glucagon-like peptide-1 (GLP-1) analogue exenatide; dipeptidyl peptidase-4 (DPP-4) inhibitors sitagliptin and vildagliptin; the long-acting insulin analogues, glargine and detemir; and to review concerns about the safety of the thiazolidinediones.
DATA SOURCES
The following databases were searched: MEDLINE (1990-April 2008), EMBASE (1990-April 2008), the Cochrane Library (all sections) Issue 2, 2008, and the Science Citation Index and ISI Proceedings (2000-April 2008). The websites of the American Diabetes Association, the European Association for the Study of Diabetes, the US Food and Drug Administration, the European Medicines Evaluation Agency and the Medicines and Healthcare Products Regulatory Agency were searched, as were manufacturers' websites.
REVIEW METHODS
Data extraction was carried out by one person, and checked by a second. Studies were assessed for quality using standard methods for reviews of trials. Meta-analyses were carried out using the Cochrane Review Manager (RevMan) software. Inclusion and exclusion criteria were based on current standard clinical practice in the UK, as outlined in NICE CG 66. The outcomes for the GLP-1 analogues, DPP-4 inhibitors and the long-acting insulin analogues were: glycaemic control, reflected by glycated haemoglobin (HbA1c) level, hypoglycaemic episodes, changes in weight, adverse events, quality of life and costs. Modelling of the cost-effectiveness of the various regimes used the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model.
RESULTS
Exenatide improved glycaemic control by around 1%, and had the added benefit of weight loss. The gliptins were effective in improving glycaemic control, reducing HbA1c level by about 0.8%. Glargine and detemir were equivalent to Neutral Protamine Hagedorn (NPH) (and to each other) in terms of glycaemic control but had modest advantages in terms of hypoglycaemia, especially nocturnal. Detemir, used only once daily, appeared to cause slightly less weight gain than glargine. The glitazones appeared to have similar effectiveness in controlling hyperglycaemia. Both can cause heart failure and fractures, but rosiglitazone appears to slightly increase the risk of cardiovascular events whereas pioglitazone reduces it. Eight trials examined the benefits of adding pioglitazone to an insulin regimen; in our meta-analysis, the mean reduction in HbA1c level was 0.54% [95% confidence interval (CI) -0.70 to -0.38] and hypoglycaemia was marginally more frequent in the pioglitazone arms [relative risk (RR) 1.27, 95% CI 0.99 to 1.63]. In most studies, those on pioglitazone gained more weight than those who were not. In terms of annual drug acquisition costs among the non-insulin regimes for a representative patient with a body mass index of around 30 kg/m2, the gliptins were the cheapest of the new drugs, with costs of between 386 pounds and 460 pounds. The glitazone costs were similar, with total annual costs for pioglitazone and for rosiglitazone of around 437 pounds and 482 pounds, respectively. Exenatide was more expensive, with an annual cost of around 830 pounds. Regimens containing insulin fell between the gliptins and exenatide in terms of their direct costs, with a NPH-based regimen having an annual cost of around 468 pounds for the representative patient, whereas the glargine and detemir regimens were more expensive, at around 634 pounds and 716 pounds, respectively. Comparisons of sitagliptin and rosiglitazone, and of vidagliptin and pioglitazone slowed clinical equivalence in terms of quality-adjusted life-years (QALYs), but the gliptins were marginally less costly. Exenatide, when compared with glargine, appeared to be cost-effective. Comparing glargine with NPH showed an additional anticipated cost of around 1800 pounds. Within the comparison of detemir and NPH, the overall treatment costs for detemir were slightly higher, at between 2700 pounds and 2600 pounds.
LIMITATIONS
The UKPDS Outcomes Model does not directly address aspects of the treatments under consideration, for example the direct utility effects from weight loss or weight gain, severe hypoglycaemic events and the fear of severe hypoglycaemic events. Also, small differences in QALYs among the drugs lead to fluctuations in incremental cost-effectiveness ratios.
CONCLUSIONS
Exenatide, the gliptins and detemir were all clinically effective. The long-acting insulin analogues glargine and detemir appeared to have only slight clinical advantages over NPH, but had much higher costs and did not appear to be cost-effective as first-line insulins for type 2 diabetes. Neither did exenatide appear to be cost-effective compared with NPH but, when used as third drug after failure of dual oral combination therapy, exenatide appeared cost-effective relative to glargine in this analysis. The gliptins are similar to the glitazones in glycaemic control and costs, and appeared to have fewer long-term side effects. Therefore, it appears, as supported by recent NICE guidelines, that NPH should be the preferred first-line insulin for the treatment of type 2 diabetes. More economic analysis is required to establish when it becomes cost-effective to switch from NPH to a long-acting analogue. Also, long-term follow-up studies of exenatide and the gliptins, and data on combined insulin and exenatide treatment, would be useful.
Topics: Adamantane; Body Weight; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Exenatide; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Nitriles; Peptides; Pyrazines; Pyrrolidines; Quality of Life; Randomized Controlled Trials as Topic; Sitagliptin Phosphate; State Medicine; Thiazolidinediones; Triazoles; United Kingdom; Venoms; Vildagliptin
PubMed: 20646668
DOI: 10.3310/hta14360 -
Current Medical Research and Opinion Jun 2010To review the cost-effectiveness of biphasic insulin aspart (BIAsp 30) compared to other insulin regimens in the treatment of type 2 diabetes based on published... (Comparative Study)
Comparative Study Review
OBJECTIVES
To review the cost-effectiveness of biphasic insulin aspart (BIAsp 30) compared to other insulin regimens in the treatment of type 2 diabetes based on published literature.
METHODS
The electronic databases MEDLINE, EMBASE, the Cochrane Library and EconLit and a selection of congress/meeting databases were systematically searched using combinations of search terms designed to identify publications describing cost-effectiveness analyses of BIAsp 30 in patients with type 2 diabetes. Searches were limited to studies in humans, and published in the English language between January 1999 and July 2009. All records were screened for inclusion in the review.
RESULTS
Seven published cost-effectiveness analyses and ten abstracts were identified. One was a health technology assessment from the UK, which evaluated cost-effectiveness using the UKPDS Outcomes Model and meta-analysis of published clinical trials and concluded that premixed insulin analogs were unlikely to be cost-effective versus insulin glargine or biphasic human insulin. In all other studies the cost-effectiveness of BIAsp 30 versus other insulin regimens was assessed using the validated CORE Diabetes Model and outcomes from either the INITIATE randomized controlled trial, or the PRESENT or IMPROVE observational studies. However, notable limitations include the fact that all cost-effectiveness analyses to date have been performed using a single model and that a number of these are based on data from observational studies rather than randomized controlled trials. Nevertheless, long-term clinical and economic outcomes were reported for several countries: UK, US, Sweden, Saudi Arabia, Poland, South Africa, South Korea and China. BIAsp 30 was associated with improvements in quality-adjusted life expectancy in all countries. Estimates of direct costs varied according to country and comparator, but incremental cost-effectiveness ratios for the US and UK were USD 46 533 and GBP 6951 per quality-adjusted life year gained for BIAsp 30 versus insulin glargine.
CONCLUSIONS
Although cost-effectiveness data on BIAsp 30 are scarce the majority of the analyses identified in this review suggest that BIAsp 30 is likely to be cost-effective compared to insulin glargine and biphasic human insulin across a wide range of settings, and under certain circumstances would be a dominant treatment option.
Topics: Biphasic Insulins; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin, Isophane; Middle Aged
PubMed: 20387997
DOI: 10.1185/03007991003689381 -
Health Technology Assessment... Feb 2010The National Institute for Health and Clinical Excellence (NICE) was reviewing its previous guidance on continuous subcutaneous insulin infusion (CSII). The review... (Review)
Review
BACKGROUND
The National Institute for Health and Clinical Excellence (NICE) was reviewing its previous guidance on continuous subcutaneous insulin infusion (CSII). The review provided an assessment of evidence which had been published since the previous NICE appraisal (TA 151) in 2007.
OBJECTIVES
To examine the clinical effectiveness and cost-effectiveness of using CSII to treat diabetes. To update the previous assessment report by reviewing evidence that has emerged since the last appraisal, and to take account of developments in alternative therapies, in particular the long-acting analogue insulins, which cause fewer problems with hypoglycaemia.
DATA SOURCES
A systematic review of the literature and an economic evaluation were carried out. The bibliographic databases used were MEDLINE and EMBASE, 2002 to June 2007. The Cochrane Library (all sections), the Science Citation Index (for meeting abstracts only) and the website of the 2007 American Diabetes Association were also searched.
REVIEW METHODS
The primary focus for type 1 diabetes mellitus (T1DM) was the comparison of CSII with multiple daily injection (MDI), based on the newer insulin analogues, but trials of neutral protamine Hagedorn (NPH)-based MDI that had been published since the last assessment were identified and described in brief. For type 2 diabetes mellitus (T2DM), all trials of MDI versus CSII were included, whether the long-acting insulin was analogue or not, because there was no evidence that analogue-based MDI was better than NPH-based MDI. Trials that were shorter than 12 weeks were excluded. Information on the patients' perspectives was obtained from four sources: the submission from the pump users group--Insulin Pump Therapy (INPUT); interviews with parents of young children who were members of INPUT; some recent studies; and from a summary of findings from the previous assessment report. Economic modelling used the Center for Outcomes Research (CORE) model, through an arrangement with the NICE and the pump manufacturers, whose submission also used the CORE model.
RESULTS
The 74 studies used for analysis included eight randomised controlled trials (RCTs) of CSII versus analogue-based MDI in either T1DM or T2DM, eight new (since the last NICE appraisal) RCTs of CSII versus NPH-based MDI in T1DM, 48 observational studies of CSII, six studies of CSII in pregnancy, and four systematic reviews. The following benefits of CSII were highlighted: better control of blood glucose levels, as reflected by glycated haemoglobin (HbA1c) levels, with the size of improvement depending on the level before starting CSII; reduction in swings in blood glucose levels, and in problems due to the dawn phenomenon; fewer problems with hypoglycaemic episodes; reduction in insulin dose per day, thereby partly off-setting the cost of CSII; improved quality of life, including a reduction in the chronic fear of severe hypoglycaemia; more flexibility of lifestyle--no need to eat at fixed intervals, more freedom of lifestyle and easier participation in social and physical activity; and benefits for the patients' family. The submission from INPUT emphasised the quality of life gains from CSII, as well as improved control and fewer hypoglycaemic episodes. Also, there was a marked discrepancy between the improvement in social quality of life reported by successful pump users, and the lack of convincing health-related quality of life gains reported in the trials. With regard to economic evaluation, the main cost of CSII is for consumables, such as tubing and cannulas, and is about 1800-2000 pounds per year. The cost of the pump, assuming 4-year life, adds another 430-720 pounds per annum. The extra cost compared with analogue-based MDI averages 1700 pounds. Most studies, assuming a reduction in HbA1c level of 1.2%, found CSII to be cost-effective.
LIMITATIONS
The most important weakness of the evidence was the very small number of randomised trials of CSII against the most modern forms of MDI, using analogue insulins.
CONCLUSIONS
Based on the totality of evidence, using observational studies to supplement the limited data from randomised trials against best MDI, CSII provides some advantages over MDI in T1DM for both children and adults. However, there was no evidence that CSII is better than analogue-based MDI in T2DM or in pregnancy. Further trials with larger numbers and longer durations comparing CSII and optimised MDI in adults, adolescents and children are needed. In addition, there should be a trial of CSII versus MDI with similar provision of structured education in both arms. A trial is also needed for pregnant women with pre-existing diabetes, to investigate using CSII to the best effect.
Topics: Adult; Aged; Child; Child, Preschool; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Female; Humans; Infusions, Subcutaneous; Insulin; Male; Treatment Outcome; United Kingdom
PubMed: 20223123
DOI: 10.3310/hta14110 -
Basic & Clinical Pharmacology &... Aug 2008Anaphylactic reactions caused by injection of protamine sulfate during cardiac surgery are a well-known complication. A systematic literature review was therefore... (Review)
Review
Anaphylactic reactions caused by injection of protamine sulfate during cardiac surgery are a well-known complication. A systematic literature review was therefore conducted to gather evidence of the knowledge concerning these side effects, and to see if any prospective randomized studies supported this. Studies investigating the effect of protamine sulfate in human beings were extracted from MEDLINE, Embase and the Cochrane Library, retrieving 487 articles. Abstracts were evaluated by both authors, and referred articles not found in the primary search were furthermore extracted from reviews and case reports, resulting in a total of 272 relevant articles. Of these, 9 retrospective studies and 16 prospective studies were performed in an evidence-based manner. However, only 3 of the 16 prospective articles had an optimal design as far as inclusion criteria, randomization, and description of symptoms were concerned. Incidence of anaphylactic reactions in the prospective studies was 0.69% compared to 0.19% in the retrospective studies, but caution should be taken due to a pronounced heterogeneity of those studies. One study found heparinase I unsuitable as replacement for protamine sulfate. Overall, our findings support the low incidence of anaphylactic reactions reported in previous studies, but of note only few prospective investigations was conducted on the subject. Our study also emphasizes the need for critical appraisal of many routine procedures: in all aspects of medical care, systematic literature review conducted in a well-structured, repeated manner should be given high priority.
Topics: Anaphylaxis; Heparin Antagonists; Humans; Prospective Studies; Protamines; Randomized Controlled Trials as Topic
PubMed: 18816305
DOI: 10.1111/j.1742-7843.2008.00274.x -
Clinical Therapeutics 2007Insulin is an effective treatment for type 2 diabetes (T2D), a progressive condition in which insulin deficiency is one of the core defects. When patients with T2D are... (Comparative Study)
Comparative Study Review
BACKGROUND
Insulin is an effective treatment for type 2 diabetes (T2D), a progressive condition in which insulin deficiency is one of the core defects. When patients with T2D are unable to achieve glycemic goals with diet and oral antihyperglycemic medications, a common starting insulin regimen consists of basal or premixed insulin added to oral antihyperglycemic medications. When glycemic goals are not achieved with the initial insulin regimen, a basal-bolus regimen is necessary.
OBJECTIVE
This article reviews clinical-trial data on the efficacy and safety profile of prandial premixed insulin analogues (insulin aspart and insulin lispro) compared with basal insulin analogues (insulin glargine, insulin detemir, and insulin lispro protamine suspension), with or without a prandial insulin analogue, in the management of T2D.
METHODS
A systematic search of Ovid, MEDLINE, and EMBASE (1995-2007) was performed to identify published randomized controlled trials comparing prandial premixed insulin analogues with basal insulin analogues, with or without prandial insulin, in patients with T2D. The search terms were premixed insulin analogues, premixed insulin, biphasic insulin aspart, insulin aspart 70/30, insulin aspart 50/50, premixed insulin lispro, insulin lispro 75/25, insulin lispro 50/50, glargine, and detemir. Abstracts presented at the 2005 and 2006 meetings of the American Diabetes Association and the European Association for the Study of Diabetes and bibliographies of the identified studies were also reviewed. Predetermined criteria for study inclusion were treatment duration of at least 12 weeks, T2D diagnosed using valid criteria, use of a basal insulin analogue (with or without rapid-acting insulin) as a study comparator, and use of well-accepted end points (eg, glycosylated hemoglobin [HbA1c], hypoglycemia, preprandial and postprandial blood glucose).
RESULTS
Of the identified randomized controlled trials, 3 studies compared premixed insulin analogues containing 70% or 75% basal and 30% or 25% rapid-acting insulin analogue with basal insulin analogues only, and 3 studies evaluated premixed insulin analogues containing 50% basal and 50% rapid-acting insulin analogue with basal insulin analogues only. Use of prandial premixed insulin analogues was associated with better overall and postprandial glycemic control. In the studies that compared twice-daily premixed insulin analogues with a basal insulin analogue, changes in HbA1c ranged from -1.00% to -2.79% and from -0.42% to -2.36%, respectively (P < 0.01). In the studies that compared thrice-daily premixed insulin analogues with a basal insulin analogue, changes in HbA1c ranged from -0.72% to -1.2% and from -0.3% to -0.75%, respectively (P < 0.01). These results were achieved with some increase in overall hypoglycemia, but not in nocturnal or severe hypoglycemia. Doses of the premixed insulin analogues were adjusted during the titration period to achieve glycemic goals.
CONCLUSIONS
The results of this systematic review suggest that regimens consisting of prandial premixed insulin analogues, which provide both basal and prandial insulin coverage, may be used as an initial insulin regimen in patients with T2D to enable better overall, preprandial, and postprandial glycemic control compared with a basal insulin analogue regimen alone. Premixed insulin analogues are an effective option for initiating and intensifying insulin therapy in patients with T2D.
Topics: Diabetes Mellitus, Type 2; Evidence-Based Medicine; Humans; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Randomized Controlled Trials as Topic
PubMed: 18046926
DOI: No ID Found -
Clinical Therapeutics Jun 2007Insulin is an effective treatment for type 2 diabetes (T2D), a progressive condition in which insulin deficiency is one of the core defects. When patients with T2D are... (Review)
Review
BACKGROUND
Insulin is an effective treatment for type 2 diabetes (T2D), a progressive condition in which insulin deficiency is one of the core defects. When patients with T2D are unable to achieve glycemic goals with diet and oral antihyperglycemic medications, a common starting insulin regimen consists of basal or premixed insulin added to oral antihyperglycemic medications. When glycemic goals are not achieved with the initial insulin regimen, a basal-bolus regimen is necessary.
OBJECTIVE
This article reviews clinical-trial data on the efficacy and safety profile of prandial premixed insulin analogues (insulin aspart and insulin lispro) compared with basal insulin analogues (insulin glargine, insulin detemir, and insulin lispro protamine suspension), with or without a prandial insulin analogue, in the management of T2D.
METHODS
A systematic search of Ovid, MEDLINE, and EMBASE (1995-2007) was performed to identify published randomized controlled trials comparing prandial premixed insulin analogues with basal insulin analogues, with or without prandial insulin, in patients with T2D. The search terms were premixed insulin analogues, premixed insulin, biphasic insulin aspart, insulin aspart 70/30, insulin aspart 50/50, premixed insulin lispro, insulin lispro 75/25, insulin lispro 50/50, glargine, and detemir. Abstracts presented at the 2005 and 2006 meetings of the American Diabetes Association and the European Association for the Study of Diabetes and bibliographies of the identified studies were also reviewed. Predetermined criteria for study inclusion were treatment duration of at least 12 weeks, T2D diagnosed using valid criteria, use of a basal insulin analogue (with or without rapid-acting insulin) as a study comparator, and use of well-accepted end points (eg, glycosylated hemoglobin [HbA(1c)], hypoglycemia, preprandial and postprandial blood glucose).
RESULTS
Of the identified randomized controlled trials, 3 studies compared premixed insulin analogues containing 70% or 75% basal and 30% or 25% rapid-acting insulin analogue with basal insulin analogues only, and 3 studies evaluated premixed insulin analogues containing 50% basal and 50% rapid-acting insulin analogue with basal insulin analogues only. Use of prandial premixed insulin analogues was associated with better overall and postprandial glycemic control. In the studies that compared twice-daily premixed insulin analogues with a basal insulin analogue, changes in HbA(1c) ranged from -1.00% to -2.79% and from -0.42% to -2.36%, respectively (P < 0.01). In the studies that compared thrice-daily premixed insulin analogues with a basal insulin analogue, changes in HbA(1c) ranged from -0.72% to -1.2% and from -0.3% to -0.75%, respectively (P < 0.01). These results were achieved with some increase in overall hypoglycemia, but not in nocturnal or severe hypoglycemia. Doses of the premixed insulin analogues were adjusted during the titration period to achieve glycemic goals.
CONCLUSIONS
The results of this systematic review suggest that regimens consisting of prandial premixed insulin analogues, which provide both basal and prandial insulin coverage, may be used as an initial insulin regimen in patients with T2D to enable better overall, preprandial, and postprandial glycemic control compared with a basal insulin analogue regimen alone. Premixed insulin analogues are an effective option for initiating and intensifying insulin therapy in patients with T2D.
Topics: Body Weight; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Evidence-Based Medicine; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Randomized Controlled Trials as Topic
PubMed: 18036388
DOI: 10.1016/j.clinthera.2007.07.003 -
Journal of Diabetes and Its... 2007Despite the evidence-based approach to management of Type 2 diabetes outlined in current diabetes practice guidelines, a large proportion of patients are achieving... (Review)
Review
Despite the evidence-based approach to management of Type 2 diabetes outlined in current diabetes practice guidelines, a large proportion of patients are achieving suboptimal glycemic control. A substantial amount of data exists comparing insulin glargine and neutral protamine Hagedorn (NPH) insulin for long-acting basal insulin coverage. The objective of this systematic review was to provide a balanced appraisal of existing clinical evidence and to determine the appropriate step in therapy for insulin glargine or NPH insulin. Relevant English language articles from 1996 to 2005 were identified through searches of the National Center for Biotechnology Information PubMed database. Search terms included neutral protamine Hagedorn, NPH, insulin glargine, insulin therapy, Type 2 diabetes, insulin analogs, HOE901, and HOE-901. Studies were compared regarding designs, primary and secondary efficacy parameters, glycosylated hemoglobin A1c (A1C), fasting plasma glucose (FPG), incidence of hypoglycemia, and other safety assessments. Six original multicenter, randomized, open-label, parallel-group trials conducted in Europe or the United States, ranging in duration from 4 to 52 weeks, met the inclusion criteria. Two additional analyses represented a subanalysis and a study extension. All of the studies compared insulin glargine with NPH insulin given once or twice daily as monotherapy or in conjunction with oral antidiabetic agents in patients with Type 2 diabetes. Based on available evidence, insulin glargine has shown equal clinical efficacy to that of NPH insulin and similar reductions in A1C and is associated with similar or lower FPG levels. Recent studies also have demonstrated that less frequent nocturnal hypoglycemia incidence is associated with insulin glargine compared with NPH insulin. The known pathophysiology of Type 2 diabetes and the need for basal insulin treatment are presented as rationale for comparison of these insulins.
Topics: Clinical Trials as Topic; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting
PubMed: 17493554
DOI: 10.1016/j.jdiacomp.2007.01.001