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Applied Health Economics and Health... Feb 2014The costs of the insulin analogue (insulin glargine) have been growing appreciably in the State of Minas Gerais in Brazil, averaging 291% per year in recent years. This... (Review)
Review
INTRODUCTION AND OBJECTIVE
The costs of the insulin analogue (insulin glargine) have been growing appreciably in the State of Minas Gerais in Brazil, averaging 291% per year in recent years. This growth has been driven by an increasing number of successful law suits and a 536% price difference between insulin glargine and neutral protamine Hagedorn (NPH) insulin. One potential way to address this is to undertake a systematic review assessing the efficacy and safety of insulin glargine analogue compared with NPH insulin in patients with type 1 diabetes mellitus (T1DM), and, as a result, provide published data to support future recommended activities by the State of Minas Gerais. These could include maintaining it on the list of the Public Health System (SUS) provided there is a price reduction. Alternatively, the review could provide potential arguments to defend against future law suits should the authorities decide to delist insulin glargine.
METHODS
A systematic review of published studies researching the effectiveness of insulin glargine in patients with T1DM between January 1970 and July 2009 in MEDLINE (PubMed), the Latin American and Caribbean Centre on Health Sciences Information, the Cochrane Controlled Trials Databases and the National Health Service Centre for Reviews and Dissemination. Inclusion criteria included insulin glargine on its own or combined with other insulin formulations. Only randomised controlled clinical trials were included. Initially, the titles of all studies were assessed by two independent reviewers before being potentially discarded, with the quality of papers assessed using a modified Jadad scale. The outcome measures included blood levels of glycated haemoglobin, episodes of hypoglycaemia, adverse effects and the reduction of microvascular and macrovascular end-organ complications of T1DM.
RESULTS
Out of 803 studies found in the selected databases, only eight trials met the inclusion criteria. Most of the studies were of poor methodological quality or had a high risk of bias, with a mean score of 2.125 on the Jadad scale. No study could be classified as double-blind, and only one study documented the increased efficacy of insulin glargine in relation to both glycaemic control and hypoglycaemic episodes. Typically, there was no significant difference between insulin glargine and NPH insulins.
CONCLUSIONS
This systematic review showed no therapeutic benefit of insulin glargine over other insulin formulations studied when analysing together glycaemic control and the frequency and severity of hypoglycaemia. We therefore recommend to the State Authority to delist insulin glargine or renegotiate a price reduction with the manufacturer. This systematic review provides support for this decision as well as documentation to combat potential law suits if discussions are unsatisfactory.
Topics: Brazil; Diabetes Mellitus, Type 1; Drug Costs; Drug Evaluation; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Prescription Fees; Randomized Controlled Trials as Topic
PubMed: 24385261
DOI: 10.1007/s40258-013-0073-6 -
Diabetes Research and Clinical Practice Dec 2011To perform a network meta-analysis between long-acting insulin analogues (glargine and detemir) and Neutral Protamine Hagedorn (NPH) insulin on adults with type 1... (Review)
Review
AIM
To perform a network meta-analysis between long-acting insulin analogues (glargine and detemir) and Neutral Protamine Hagedorn (NPH) insulin on adults with type 1 diabetes.
METHODS
A systematic review of the literature was conducted according to the Cochrane Collaboration guidelines. The search for randomized controlled trials was performed in process databases, conferences and "gray literature" by 1995.
RESULTS
We found 1051 citations comparing glargine or detemir with human insulin and 187 comparing long-acting insulin analogues. Data on Glycated Hemoglobin (HbA1c), hypoglycemia episodes, nocturnal hypoglycemia and withdrawal were meta-analyzed. After review, 8 studies comparing glargine and 9 comparing detemir with NPH and 2 comparing glargine with detemir were considered relevant. Were included 1508 patients that received glargine, 2698 detemir and 2654 NPH insulin. Efficacy data showed no significant differences in HbA1c change between glargine or detemir (once daily) and NPH insulin. Twice-daily regimen of detemir caused a difference in HbA1c that favored detemir (-0.14% [95% CI -0.21 to -0.08]). Direct comparisons showed no significant differences between glargine and detemir in safety or HbA1c mean change.
CONCLUSION
The long-acting insulin analogues offer little to no clinical advantages over NPH insulin, and there is no significant difference in the efficacy and safety.
Topics: Adult; Diabetes Mellitus, Type 1; Humans; Hypoglycemic Agents; Insulin, Long-Acting
PubMed: 21992870
DOI: 10.1016/j.diabres.2011.09.001 -
The Cochrane Database of Systematic... Jul 2013The Cystic Fibrosis Foundation recommends both short-term and long-acting insulin therapy when cystic fibrosis-related diabetes has been diagnosed. Diagnosis is based... (Review)
Review
BACKGROUND
The Cystic Fibrosis Foundation recommends both short-term and long-acting insulin therapy when cystic fibrosis-related diabetes has been diagnosed. Diagnosis is based on: an elevated fasting blood glucose level greater than 6.94 mmol/liter (125 mg/deciliter); or symptomatic diabetes for random glucose levels greater than 11.11 mmol/liter (200 mg/deciliter); or glycated hemoglobin levels of at least 6.5%.
OBJECTIVES
To establish the effectiveness of agents for managing diabetes in people with cystic fibrosis in relation to blood sugar levels, lung function and weight management.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also handsearched abstracts from pulmonary symposia and the North American Cystic Fibrosis Conferences.Date of the most recent search of the Group's Cystic Fibrosis Trials Register: 22 July 2013.
SELECTION CRITERIA
Randomized controlled trials comparing all methods of diabetes therapy in people with diagnosed cystic fibrosis-related diabetes.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed the risk of bias in the included studies.
MAIN RESULTS
The searches identified 19 studies (28 references). Three studies (107 participants) are included: one comparing insulin with oral repaglinide and no medication (short-term single-center study of seven patients with cystic fibrosis-related diabetes and normal fasting glucose); one comparing insulin with oral repaglinide and placebo (long-term multi-center study with 81 patients, 61 of whom had cystic fibrosis-related diabetes); and one 12-week single-center study comparing the long-acting insulin, glargine to short-term neutral protamine Hagedorn insulin. The long-term trial of insulin and repaglinide demonstrated no significant difference between treatments. In the smaller study comparing insulin and oral repaglinide, there were two incidents of significant hypoglycemia in the insulin group compared to one in the repaglinide group; in the larger study there were five incidents of significant hypoglycemia in the insulin group and six in the repaglinide group. The study comparing glargine to neutral protamine Hagedorn insulin demonstrated a statistically non-significant weight increase in with longer-acting insulin given at bedtime and reported a mean of six hypoglycemia events in the glargine group compared to five events in the neutral protamine Hagedorn insulin group. None of the three included studies were powered to show a significant improvement in lung function.
AUTHORS' CONCLUSIONS
This review has not found any significant conclusive evidence that long-acting insulins, short-acting insulins or oral hypoglycemic agents have a distinct advantage over one another in controlling hyperglycemia or clinical outcomes associated with cystic fibrosis-related diabetes. While some cystic fibrosis centers use oral medications to help control diabetes, the Cystic Fibrosis Foundation (USA) clinical practice guidelines support the use of insulin therapy and this remains the most widely-used treatment method. Randomized controlled trials specifically related to controlling diabetes with this impact on the course of pulmonary disease process in cystic fibrosis continue to be a high priority.There is no demonstrated advantage yet established for using oral hypoglycemic agents over insulin, and further studies need to be evaluated to establish whether there is clear benefit for using hypoglycemic agents. Agents that potentiate insulin action, especially agents with additional anti-inflammatory potential should be further investigated to see if there may be a clinical advantage to adding these medications to insulin as adjuvant therapy.
Topics: Administration, Oral; Cystic Fibrosis; Diabetes Mellitus; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Randomized Controlled Trials as Topic
PubMed: 23893261
DOI: 10.1002/14651858.CD004730.pub3 -
American Journal of Health-system... Apr 2015The comparative efficacy, safety, and cost-effectiveness of rapid and long-acting insulin analogs compared with regular or neutral protamine Hagedorn nonanalog insulins... (Comparative Study)
Comparative Study Meta-Analysis Review
PURPOSE
The comparative efficacy, safety, and cost-effectiveness of rapid and long-acting insulin analogs compared with regular or neutral protamine Hagedorn nonanalog insulins or with oral antidiabetic agents in hospitalized adults were evaluated.
METHODS
A literature search was conducted to identify studies that compared the effects of rapid-acting, long-acting, or mixed insulin analogs with short- or intermediate-acting insulin or any other oral antidiabetic medication.
RESULTS
Twenty-three primary studies were included in the review. Rapid-acting analogs and basal-bolus analog regimens were found to reduce the duration of hospital stay by approximately one day compared with regular insulin and basal-bolus nonanalog regimens. One large cohort study found an adjusted 48% relative risk reduction in mortality with rapid-acting analogs versus regular insulin in a heterogeneous hospitalized hyperglycemic population. A randomized controlled trial found a significant reduction in postoperative complications with basal-bolus analogs compared with basal-bolus nonanalog insulin. When compared with regular sliding-scale insulin (SSI), fixed-dose insulin glargine with or without insulin glulisine was found to reduce the blood glucose concentration in patients with type 2 diabetes and reduce postoperative complications in surgical patients with diabetes. The quality of evidence was primarily very low or low for most outcomes.
CONCLUSION
A systematic literature review revealed a very low or low quality of evidence, suggesting that, compared with nonanalog regimens, rapid-acting insulin analogs reduce the duration of hospital stay and mortality rates and that basal- bolus analog regimens may reduce the duration of hospital stay and postoperative complications. There is also a low quality of evidence to suggest that a fixed-dose analog regimen of insulin glargine with or without insulin glulisine is more effective than regular SSI for reducing blood glucose concentrations and postoperative complications.
Topics: Cost-Benefit Analysis; Hospitalization; Humans; Insulin
PubMed: 25788506
DOI: 10.2146/ajhp140161 -
Transfusion Medicine (Oxford, England) Apr 2012To conduct a systematic review of the literature to answer the question: Has administration of recombinant activated factor VII (rFVIIa) or prothombin complex... (Review)
Review
OBJECTIVES
To conduct a systematic review of the literature to answer the question: Has administration of recombinant activated factor VII (rFVIIa) or prothombin complex concentrate (PCC) or activated PCC (aPCC) been demonstrated to be effective in reversing pendasaccharide anticoagulants (PSAs)?
BACKGROUND
Fondaparinux and idraparinux are ultra-short, synthetic PSAs. Typical anticoagulation reversal with either vitamin K and fresh frozen plasma or protamine sulphate does not reverse PSAs. Mechanistically, it is plausible that rFVIIa, PCC and aPCC may be effective reversal agents for PSAs. However, the available data are limited.
MATERIALS/METHODS
We conducted a systematic review of MEDLINE, EMBASE, CINAHL and the Cochrane Library without date or language limitations designed to answer the question: Has administration of rFVIIa, PCC or aPCC been demonstrated to be effective in reversing PSAs? The quality of the included studies was assessed based on standard methodologies. Relevant information was synthesised and reported.
RESULTS
After an initial literature search, 197 abstracts were identified, of which 14 articles were reviewed in their entirety. Ultimately, five studies were identified that met inclusion and exclusion criteria. Although the literature is limited, the best available data support the use of rFVIIa for serious bleeding in patients anticoagulated with PSAs.
CONCLUSIONS
Limited data support the use of rFVIIa as a reversal agent for serious bleeding in patients who are anticoagulated with PSAs. The optimal dose, role for concomitant use of platelets or antifibrinolytic agents and exact indications for reversal remain to be determined. Such investigations are urgently needed as use of PSAs increases.
Topics: Anticoagulants; Blood Coagulation Factors; Factor VIIa; Heparin, Low-Molecular-Weight; Humans; MEDLINE; Protein C; Recombinant Proteins
PubMed: 22171588
DOI: 10.1111/j.1365-3148.2011.01125.x -
BMJ Open Nov 2022To examine the comparative efficacy and complications of long-acting and intermediate-acting insulin for different patient characteristics for type 1 diabetes mellitus... (Meta-Analysis)
Meta-Analysis
Comparative efficacy and complications of long-acting and intermediate-acting insulin regimens for adults with type 1 diabetes: an individual patient data network meta-analysis.
OBJECTIVE
To examine the comparative efficacy and complications of long-acting and intermediate-acting insulin for different patient characteristics for type 1 diabetes mellitus (T1DM).
DESIGN
Systematic review and individual patient data (IPD) network meta-analysis (NMA).
DATA SOURCES
MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched through June 2015.
ELIGIBILITY CRITERIA
Randomised controlled trials (RCTs) on adults with T1DM assessing glycosylated haemoglobin (A1c) and severe hypoglycaemia in long-acting and intermediate-acting insulin regimens.
DATA EXTRACTION AND SYNTHESIS
We requested IPD from authors and funders. When IPD were not available, we used aggregate data. We conducted a random-effects model, and specifically a one-stage IPD-NMA for those studies providing IPD and a two-stage IPD-NMA to incorporate those studies not providing IPD.
RESULTS
We included 28 RCTs plus one companion report, after screening 6680 titles/abstracts and 205 full-text articles. Of the 28 RCTs, 27 studies provided data for the NMA with 7394 participants, of which 12 RCTs had IPD on 4943 participants. The IPD-NMA for A1c suggested that glargine once daily (mean difference [MD]=-0.31, 95% confidence interval [CI]: -0.48 to -0.14) and detemir once daily (MD=-0.25, 95% CI: -0.41 to -0.09) were superior to neutral protamine Hagedorn (NPH) once daily. NPH once/two times per day improved A1c compared with NPH once daily (MD=-0.30, 95% CI: -0.50 to -0.11). Results regarding complications in severe hypoglycaemia should be considered with great caution due to inconsistency in the evidence network. Accounting for missing data, there was no evidence of inconsistency and long-acting insulin regimens ranked higher regarding reducing severe hypoglycaemia compared with intermediate-acting insulin regimens (two-stage NMA: glargine two times per day SUCRA (Surface Under the Cumulative Ranking curve)=89%, detemir once daily SUCRA=77%; one-stage NMA: detemir once daily/two times per day SUCRA=85%). Using multiple imputations and IPD only, complications in severe hypoglycaemia increased with diabetes-related comorbidities (regression coefficient: 1.03, 95% CI: 1.02 to 1.03).
CONCLUSIONS
Long-acting insulin regimens reduced A1c compared with intermediate-acting insulin regimens and were associated with lower severe hypoglycaemia. Of the observed differences, only glargine once daily achieved a clinically significant reduction of 0.30%. Results should be interpreted with caution due to very low quality of evidence.
PROSPERO REGISTRATION NUMBER
CRD42015023511.
Topics: Adult; Humans; Diabetes Mellitus, Type 1; Insulin Glargine; Glycated Hemoglobin; Hypoglycemic Agents; Network Meta-Analysis; Insulin, Long-Acting; Insulin; Hypoglycemia; Insulin, Isophane
PubMed: 36332950
DOI: 10.1136/bmjopen-2021-058034 -
Endocrine Practice : Official Journal... Nov 2022Optimal glucocorticoid-induced hyperglycemia (GCIH) management is unclear. The COVID-19 pandemic has made this issue more prominent because dexamethasone became the... (Review)
Review
OBJECTIVE
Optimal glucocorticoid-induced hyperglycemia (GCIH) management is unclear. The COVID-19 pandemic has made this issue more prominent because dexamethasone became the standard of care in patients needing respiratory support. This systematic review aimed to describe the management of GCIH and summarize available management strategies for dexamethasone-associated hyperglycemia in patients with COVID-19.
METHODS
A systematic review was conducted using the PubMed/MEDLINE, Cochrane Library, Embase, and Web of Science databases with results from 2011 through January 2022. Keywords included synonyms for "steroid-induced diabetes" or "steroid-induced hyperglycemia." Randomized controlled trials (RCTs) were included for review of GCIH management. All studies focusing on dexamethasone-associated hyperglycemia in COVID-19 were included regardless of study quality.
RESULTS
Initial search for non-COVID GCIH identified 1230 references. After screening and review, 33 articles were included in the non-COVID section of this systematic review. Initial search for COVID-19-related management of dexamethasone-associated hyperglycemia in COVID-19 identified 63 references, whereas 7 of these were included in the COVID-19 section. RCTs of management strategies were scarce, did not use standard definitions for hyperglycemia, evaluated a variety of treatment strategies with varying primary end points, and were generally not found to be effective except for Neutral Protamine Hagedorn insulin added to basal-bolus regimens.
CONCLUSION
Few RCTs are available evaluating GCIH management. Further studies are needed to support the formulation of clinical guidelines for GCIH especially given the widespread use of dexamethasone during the COVID-19 pandemic.
Topics: Humans; Glucocorticoids; Hyperglycemia; Dexamethasone; Steroids; COVID-19 Drug Treatment
PubMed: 35940469
DOI: 10.1016/j.eprac.2022.07.014 -
The Cochrane Database of Systematic... Apr 2016The Cystic Fibrosis Foundation recommends both short-term and long-acting insulin therapy when cystic fibrosis-related diabetes has been diagnosed. Diagnosis is based... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The Cystic Fibrosis Foundation recommends both short-term and long-acting insulin therapy when cystic fibrosis-related diabetes has been diagnosed. Diagnosis is based on: an elevated fasting blood glucose level greater than 6.94 mmol/liter (125 mg/deciliter); or oral glucose tolerance tests greater than 11.11 mmol/liter (200 mg/deciliter) at two hours; or symptomatic diabetes for random glucose levels greater than 11.11 mmol/liter (200 mg/deciliter); or glycated hemoglobin levels of at least 6.5%.
OBJECTIVES
To establish the effectiveness of insulin and oral agents for managing diabetes in people with cystic fibrosis in relation to blood sugar levels, lung function and weight management.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also handsearched abstracts from pulmonary symposia and the North American Cystic Fibrosis Conferences.Date of the most recent search of the Group's Cystic Fibrosis Trials Register: 18 February 2016.
SELECTION CRITERIA
Randomized controlled trials comparing all methods of diabetes therapy in people with diagnosed cystic fibrosis-related diabetes.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed the risk of bias in the included studies.
MAIN RESULTS
The searches identified 22 trials (34 references). Four trials (200 participants) are included: one short-term single-center trial (n = 7) comparing insulin with oral repaglinide and no medication in people with cystic fibrosis-related diabetes and normal fasting glucose; one long-term multicenter trial (n = 100, 74 of whom had cystic fibrosis-related diabetes) comparing insulin with oral repaglinide and placebo; one long-term multicenter trial (n = 73) comparing insulin with oral repaglinide; and one 12-week single-center trial (n = 20) comparing the long-acting insulin glargine to short-term neutral protamine Hagedorn insulin.Two trials with data for the comparison of insulin to placebo did not report any significant differences between groups for the primary outcomes of blood glucose levels, lung function and nutritional status. This was also true for the single trial with data for the comparison of repaglinide to placebo. Two trials (one lasting one year and one lasting two years) contributed data for the comparison of insulin versus repaglinide. There were no significant differences for the primary outcomes at any time point, except at one year (in the two-year trial) when the insulin group had significant improvement in z score for body mass index compared to the repaglinide group. The single trial comparing glargine to neutral protamine Hagedorn insulin also did not report any significant differences in the review's primary outcomes. A few cases of hypoglycemia were seen in three out of the four trials (none in the longest trial), but these events resolved without further treatment.There was an unclear risk of bias from randomization and allocation concealment in two of the four included trials as the authors did not report any details; in the remaining two studies details for randomization led to a low risk of bias, but only one had sufficient details on allocation concealment to allow a low risk judgement, the second was unclear. There was a high risk from blinding for all trials (except for the comparison of oral repaglinide versus placebo) due to the nature of the interventions. Complete data for all outcomes were not available from any trial leading to a high risk of reporting bias. The amounts of insulin and repaglinide administered were not comparable and this may lead to bias in the results. None of the included trials were powered to show a significant improvement in lung function.
AUTHORS' CONCLUSIONS
This review has not found any significant conclusive evidence that long-acting insulins, short-acting insulins or oral hypoglycemic agents have a distinct advantage over one another in controlling hyperglycemia or clinical outcomes associated with cystic fibrosis-related diabetes. While some cystic fibrosis centers use oral medications to help control diabetes, the Cystic Fibrosis Foundation (USA) clinical practice guidelines support the use of insulin therapy and this remains the most widely-used treatment method. Randomized controlled trials specifically related to controlling diabetes with this impact on the course of pulmonary disease process in cystic fibrosis continue to be a high priority.There is no demonstrated advantage yet established for using oral hypoglycemic agents over insulin, and further trials need to be evaluated to establish whether there is clear benefit for using hypoglycemic agents. Agents that potentiate insulin action, especially agents with additional anti-inflammatory potential should be further investigated to see if there may be a clinical advantage to adding these medications to insulin as adjuvant therapy.
Topics: Administration, Oral; Carbamates; Cystic Fibrosis; Diabetes Mellitus; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane; Piperidines; Randomized Controlled Trials as Topic
PubMed: 27087121
DOI: 10.1002/14651858.CD004730.pub4 -
Current Research in Microbial Sciences 2022The high prevalence of nosocomial infections is related to the use of medical insertion devices such as central venous catheters (CVCs). Most of the microorganisms...
The high prevalence of nosocomial infections is related to the use of medical insertion devices such as central venous catheters (CVCs). Most of the microorganisms causing nosocomial infections are biofilm producers, this characteristic allows them to adhere to abiotic surfaces and cause initial catheter infections that can lead to bloodstream infections. Our main goal in this systematic review was to evaluate the prevalence of biofilm among CVC-related infections, particularly among Intensive Care Unit (ICU) patients, in the studies applying different and methodologies. All studies reporting clinical isolates from patients with catheter-related nosocomial infections and biofilm evaluation published up to 24 June 2022 in the PubMed and Scopus databases were included. Twenty-five studies met the eligibility criteria and were included in this systematic review for analysis. Different methodologies were applied in the assessment of biofilm-forming microorganisms including assays, catheter-infected , and mouse models. The present study showed that between 59 and 100% of clinical isolates were able to form biofilms, and the prevalence rate of biofilm formation varied significantly between studies from different countries and regions. Among the clinical isolates collected in our study set, a wide variety of microorganisms including Gram-positive strains, Gram-negative strains, and were found. Many authors studied resistance mechanisms and genes related to biofilm development and surface adherence properties. In some cases, the studies also evaluated biofilm inhibition assays using various kinds of catheter coatings.
PubMed: 36518176
DOI: 10.1016/j.crmicr.2022.100175 -
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