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Diabetes Therapy : Research, Treatment... Jun 2016The use of insulin analogs for the treatment of type 1 diabetes mellitus (T1DM) is widespread; however, the therapeutic benefits still require further evaluation given...
INTRODUCTION
The use of insulin analogs for the treatment of type 1 diabetes mellitus (T1DM) is widespread; however, the therapeutic benefits still require further evaluation given their higher costs. The objective of this study was to evaluate the effectiveness and safety of analog insulin glargine compared to recombinant DNA (rDNA) insulin in patients with T1DM in observational studies, building on previous reviews of randomized controlled trials comparing neutral protamine Hagedorn insulin and insulin glargine.
METHODS
A systematic review with a meta-analysis was performed. The review included cohort studies and registries available on PubMed, LILACS, and the Cochrane Central Register of Controlled Trials (CENTRAL), as well as manual and gray literature searches. The meta-analysis was conducted in Review Manager 5.3 software. The primary outcomes were glycated hemoglobin (Hb1Ac), weight gain, and hypoglycemia. Methodological quality was assessed using the Newcastle-Ottawa scale.
RESULTS
Out of 796 publications, 11 studies were finally included. The meta-analysis favored insulin glargine in HbA1c outcomes (adult patients) and hypoglycemic episodes (P < 0.05), but without reaching glycemic control (Hb1Ac to approximately 7%). The methodological quality of the studies was moderate, noting that 45% of studies were funded by pharmaceutical companies.
CONCLUSION
Given the high heterogeneity of the studies, the discrete value presented by the estimated effect on effectiveness and safety, potential conflicts of interest of the studies, and the appreciable higher cost of insulin glargine, there is still no support for recommending first-line therapy with analogs. The role of analogs in the treatment of T1DM could be better determined by further observational studies of good methodological quality to assess their long-term effectiveness and safety, as well as their cost-effectiveness.
PubMed: 27048292
DOI: 10.1007/s13300-016-0166-y -
BMJ Open Feb 2016To compare the efficacy and safety of a concentrated formulation of insulin glargine (Gla-300) with other basal insulin therapies in patients with type 2 diabetes... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To compare the efficacy and safety of a concentrated formulation of insulin glargine (Gla-300) with other basal insulin therapies in patients with type 2 diabetes mellitus (T2DM).
DESIGN
This was a network meta-analysis (NMA) of randomised clinical trials of basal insulin therapy in T2DM identified via a systematic literature review of Cochrane library databases, MEDLINE and MEDLINE In-Process, EMBASE and PsycINFO.
OUTCOME MEASURES
Changes in HbA1c (%) and body weight, and rates of nocturnal and documented symptomatic hypoglycaemia were assessed.
RESULTS
41 studies were included; 25 studies comprised the main analysis population: patients on basal insulin-supported oral therapy (BOT). Change in glycated haemoglobin (HbA1c) was comparable between Gla-300 and detemir (difference: -0.08; 95% credible interval (CrI): -0.40 to 0.24), neutral protamine Hagedorn (NPH; 0.01; -0.28 to 0.32), degludec (-0.12; -0.42 to 0.20) and premixed insulin (0.26; -0.04 to 0.58). Change in body weight was comparable between Gla-300 and detemir (0.69; -0.31 to 1.71), NPH (-0.76; -1.75 to 0.21) and degludec (-0.63; -1.63 to 0.35), but significantly lower compared with premixed insulin (-1.83; -2.85 to -0.75). Gla-300 was associated with a significantly lower nocturnal hypoglycaemia rate versus NPH (risk ratio: 0.18; 95% CrI: 0.05 to 0.55) and premixed insulin (0.36; 0.14 to 0.94); no significant differences were noted in Gla-300 versus detemir (0.52; 0.19 to 1.36) and degludec (0.66; 0.28 to 1.50). Differences in documented symptomatic hypoglycaemia rates of Gla-300 versus detemir (0.63; 0.19 to 2.00), NPH (0.66; 0.27 to 1.49) and degludec (0.55; 0.23 to 1.34) were not significant. Extensive sensitivity analyses supported the robustness of these findings.
CONCLUSIONS
NMA comparisons are useful in the absence of direct randomised controlled data. This NMA suggests that Gla-300 is also associated with a significantly lower risk of nocturnal hypoglycaemia compared with NPH and premixed insulin, with glycaemic control comparable to available basal insulin comparators.
Topics: Body Weight; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine
PubMed: 26880669
DOI: 10.1136/bmjopen-2015-009421 -
Acta Diabetologica Aug 2015A variety of basal insulin preparations are used to treat patients with type 2 diabetes mellitus (T2DM). We aimed to summarize scientific evidence on relative efficacy... (Meta-Analysis)
Meta-Analysis Review
Systematic review and meta-analysis of randomized clinical trials comparing efficacy and safety outcomes of insulin glargine with NPH insulin, premixed insulin preparations or with insulin detemir in type 2 diabetes mellitus.
AIMS
A variety of basal insulin preparations are used to treat patients with type 2 diabetes mellitus (T2DM). We aimed to summarize scientific evidence on relative efficacy and safety of insulin glargine (IGlar) and other insulins in T2DM.
METHODS
A systematic review was carried out in major medical databases up to December 2012. Relevant studies compared efficacy and safety of IGlar, added to oral drugs (OAD) or/and in combination with bolus insulin, with protamine insulin (NPH) or premixed insulin (MIX) in the same regimen, as well as with insulin detemir (IDet), in T2DM. Target HbA1c level without hypoglycemic events was considered the primary endpoint.
RESULTS
Twenty eight RCTs involving 12,669 T2DM patients followed for 12-52 weeks were included in quantitative analysis. IGlar + OAD use was associated with higher probability of reaching target HbA1c level without hypoglycemia as compared to NPH + OAD (RR = 1.32 [1.09, 1.59]) or MIX without OAD (RR = 1.61 [1.22, 2.13]) and similar effect as IDet + OAD (RR = 1.07 [0.87, 1.33]) and MIX + OAD (RR = 1.09 [0.86, 1.38]). IGlar + OAD demonstrated significantly lower risk of symptomatic hypoglycemia as compared to NPH + OAD (RR = 0.89 [0.83, 0.96]), MIX + OAD (RR = 0.75 [0.68, 0.83]) and MIX without OAD(RR = 0.75 [0.68, 0.83]), but not with IDet + OAD (RR = 0.99 [0.90, 1.08]). In basal-bolus regimens, IGlar demonstrated similar proportion of T2DM patients achieving target HbA1c as compared to NPH (RR = 1.14 [0.91, 1.44]) but higher than MIX (RR = 1.26 [1.12, 1.42) or IDet (RR = 1.38 [1.11, 1.72]). The risk of severe hypoglycemia was lower in IGlar than in NPH (RR = 0.77 [0.63, 0.94]), with no differences in comparison with MIX (RR = 0.74 [0.46, 1.20]) and IDet (RR = 1.10 [0.54, 2.25]). IGlar + OAD has comparable safety profile to NPH, with less frequent adverse events leading to treatment discontinuation than MIX + OAD (RR = 0.41 [0.22, 0.76]) and IDet + OAD (RR = 0.40 [0.24, 0.69]). Also severe adverse reactions were less common for IGlar + OAD when compared to MIX + OAD (RR = 0.71 [0.52; 0.98]).
CONCLUSION
For the majority of examined efficacy and safety outcomes, IGlar use in T2DM patients was superior or non-inferior to the alternative insulin treatment options.
Topics: Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25585592
DOI: 10.1007/s00592-014-0698-4 -
BMJ Open Dec 2014To evaluate the effectiveness and safety of dipeptidyl peptidase-4 (DPP-4) inhibitors versus intermediate-acting insulin for adults with type 2 diabetes mellitus (T2DM)... (Comparative Study)
Comparative Study Meta-Analysis Review
Safety and effectiveness of dipeptidyl peptidase-4 inhibitors versus intermediate-acting insulin or placebo for patients with type 2 diabetes failing two oral antihyperglycaemic agents: a systematic review and network meta-analysis.
OBJECTIVE
To evaluate the effectiveness and safety of dipeptidyl peptidase-4 (DPP-4) inhibitors versus intermediate-acting insulin for adults with type 2 diabetes mellitus (T2DM) and poor glycaemic control despite treatment with two oral agents.
SETTING
Studies were multicentre and multinational.
PARTICIPANTS
Ten studies including 2967 patients with T2DM.
INTERVENTIONS
Studies that examined DPP-4 inhibitors compared with each other, intermediate-acting insulin, no treatment or placebo in patients with T2DM.
PRIMARY AND SECONDARY OUTCOME MEASURES
Primary outcome was glycosylated haemoglobin (HbA1c). Secondary outcomes were healthcare utilisation, body weight, fractures, quality of life, microvascular complications, macrovascular complications, all-cause mortality, harms, cost and cost-effectiveness.
RESULTS
10 randomised clinical trials with 2967 patients were included after screening 5831 titles and abstracts, and 180 full-text articles. DPP-4 inhibitors significantly reduced HbA1c versus placebo in network meta-analysis (NMA; mean difference (MD) -0.62%, 95% CI -0.93% to -0.33%) and meta-analysis (MD -0.61%, 95% CI -0.81% to -0.41%), respectively. Significant differences in HbA1c were not observed for neutral protamine Hagedorn (NPH) insulin versus placebo and DPP-4 inhibitors versus NPH insulin in NMA. In meta-analysis, no significant differences were observed between DPP-4 inhibitors and placebo for severe hypoglycaemia, weight gain, cardiovascular disease, overall harms, treatment-related harms and mortality, although patients receiving DPP-4 inhibitors experienced less infections (relative risk 0.72, 95% CI 0.57 to 0.91).
CONCLUSIONS
DPP-4 inhibitors were superior to placebo in reducing HbA1c levels in adults with T2DM taking at least two oral agents. Compared with placebo, no safety signals were detected with DPP-4 inhibitors and there was a reduced risk of infection. There was no significant difference in HbA1c observed between NPH and placebo or NPH and DPP-4 inhibitors.
TRIAL REGISTRATION NUMBER
PROSPERO # CRD42013003624.
Topics: Diabetes Mellitus, Type 2; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Incretins; Insulin; Insulin, Isophane; Treatment Outcome
PubMed: 25537781
DOI: 10.1136/bmjopen-2014-005752 -
BMJ (Clinical Research Ed.) Oct 2014To examine the safety, effectiveness, and cost effectiveness of long acting insulin for type 1 diabetes. (Comparative Study)
Comparative Study Meta-Analysis Review
Safety, effectiveness, and cost effectiveness of long acting versus intermediate acting insulin for patients with type 1 diabetes: systematic review and network meta-analysis.
OBJECTIVE
To examine the safety, effectiveness, and cost effectiveness of long acting insulin for type 1 diabetes.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Medline, Cochrane Central Register of Controlled Trials, Embase, and grey literature were searched through January 2013.
STUDY SELECTION
Randomized controlled trials or non-randomized studies of long acting (glargine, detemir) and intermediate acting (neutral protamine Hagedorn (NPH), lente) insulin for adults with type 1 diabetes were included.
RESULTS
39 studies (27 randomized controlled trials including 7496 patients) were included after screening of 6501 titles/abstracts and 190 full text articles. Glargine once daily, detemir once daily, and detemir once/twice daily significantly reduced hemoglobin A1c compared with NPH once daily in network meta-analysis (26 randomized controlled trials, mean difference -0.39%, 95% confidence interval -0.59% to -0.19%; -0.26%, -0.48% to -0.03%; and -0.36%, -0.65% to -0.08%; respectively). Differences in network meta-analysis were observed between long acting and intermediate acting insulin for severe hypoglycemia (16 randomized controlled trials; detemir once/twice daily versus NPH once/twice daily: odds ratio 0.62, 95% confidence interval 0.42 to 0.91) and weight gain (13 randomized controlled trials; detemir once daily versus NPH once/twice daily: mean difference 4.04 kg, 3.06 to 5.02 kg; detemir once/twice daily versus NPH once daily: -5.51 kg, -6.56 to -4.46 kg; glargine once daily versus NPH once daily: -5.14 kg, -6.07 to -4.21). Compared with NPH, detemir was less costly and more effective in 3/14 cost effectiveness analyses and glargine was less costly and more effective in 2/8 cost effectiveness analyses. The remaining cost effectiveness analyses found that detemir and glargine were more costly but more effective than NPH. Glargine was not cost effective compared with detemir in 2/2 cost effectiveness analyses.
CONCLUSIONS
Long acting insulin analogs are probably superior to intermediate acting insulin analogs, although the difference is small for hemoglobin A1c. Patients and their physicians should tailor their choice of insulin according to preference, cost, and accessibility.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42013003610.
Topics: Cost-Benefit Analysis; Diabetes Mellitus, Type 1; Humans; Hypoglycemic Agents; Insulin, Long-Acting
PubMed: 25274009
DOI: 10.1136/bmj.g5459 -
Journal of Vascular and Interventional... May 2014We provide an assessment of clinical, angiographic, and procedure related risk factors associated with stroke and/or death in patients undergoing carotid artery stent...
BACKGROUND AND PURPOSE
We provide an assessment of clinical, angiographic, and procedure related risk factors associated with stroke and/or death in patients undergoing carotid artery stent placement which will assist in patient stratification and identification of high-stent risk patients.
METHODS
A comprehensive search of Medline from January 1st 1996 to December 31st 2011 was performed with key words "carotid artery stenosis", " carotid artery stenting", "carotid artery stent placement", "death" , " mortality", "stroke", "outcome", "clinical predictors", "angiographic predictors", was performed in various combinations. We independently abstracted data and assessed the quality of the studies. This analysis led to the selection of 71 articles for review.
RESULTS
Clinical factors including age≥80 years, symptomatic status, procedure within 2 weeks of symptoms, chronic renal failure, diabetes mellitus, and hemispheric TIA were associated with stroke (ischemic or hemorrhagic) and death within 1 month after carotid artery stent placement. Angiographic factors including left carotid artery intervention, stenosis > 90%, ulcerated and calcified plaques, lesion length > 10mm, thrombus at the site, ostial involvement, predilation without EPD, ICA-CCA angulation > 60%, aortic arch type III, and aortic arch calcification were also associated with 1 month stroke and/or death. Intra-procedural platelet GP IIb/IIIa inhibitors, protamine use, multiple stents, predilatation prior to stent placement were associated with stroke (ischemic or hemorrhagic) and death after carotid artery stent placement. Intraprocedural use of embolic protection devices and stent design (open versus closed cell design) did not demonstrate a consistent relationship with 1 month stroke and/or death. Procedural statin use, and operator and center experience of more than 50 procedures per year were protective for 1 month stroke and/or death.
CONCLUSIONS
Our review identified risk factors for stroke, death, and MI within 1 month in patients undergoing carotid artery stent placement. Such information will result in better patient selection for carotid artery stent placement particularly in those who are also candidates for carotid endarterectomy.
PubMed: 24920983
DOI: No ID Found -
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 -
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 -
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