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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 -
International Journal of Clinical... Mar 2014It is uncertain whether the addition of biphasic insulin analogues to oral antidiabetic drugs (OADs) is as effective and safe as basal insulin in patients with type 2... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
It is uncertain whether the addition of biphasic insulin analogues to oral antidiabetic drugs (OADs) is as effective and safe as basal insulin in patients with type 2 diabetes mellitus (T2DM). We performed a systematic review to compare glycaemic control and selected clinical outcomes in T2DM patients inadequately controlled with OADs whose treatment was intensified by adding biphasic insulin aspart (BIAsp 30) or insulin glargine (IGlar).
METHODS
The analysis included randomised controlled trials (RCTs) identified by a systematic literature search in medical databases (MEDLINE, EMBASE, The Cochrane Library and other sources) up to March 2013. Studies met the inclusion criteria if they compared BIAsp 30 vs. IGlar added to at least one OAD in T2DM patients. Trials applying different OADs in both treatment arms were also included. Results were presented as weighted mean difference (WMD) or odds ratio (OR) with a 95% confidence interval (CI).
RESULTS
Five trials, including a total number of 1758 patients followed up from 24 to 28 weeks, were identified. Quantitative synthesis demonstrated that BIAsp 30 reduced HbA1c level more efficiently than IGlar [5 RCTs; WMD (95% CI): -0.21% (-0.35%, -0.08%)]. Differences were observed in favour of BIAsp for lower mean prandial glucose increment [3 RCTs; WMD (95% CI): -14.70 mg/dl (-20.09, -9.31)]; no difference was observed for fasting plasma glucose [3 RCTs; WMD (95% CI): 7.09 mg/dl (-15.76, 29.94)]. We found no evidence for higher risk of overall [2 RCTs; 63% vs. 51%; OR = 1.77 (0.91; 3.44)] and severe hypoglycaemic episodes [4 RCTs; 0.98% vs. 1.12%; OR (95% CI) = 0.88 (0.31, 2.53)] in the BIAsp 30 group as compared with IGlar group. Twice-daily administration of BIAsp 30 resulted in larger weight gain [2 RCTs; WMD (95% CI) = 1.78 kg (1.04; 2.52)].
CONCLUSIONS
BIAsp 30 added to OAD therapy results in a better glycaemic control as compared with IGlar in T2DM patients. BIAsp 30 use is associated with slightly larger weight gain but no rise in risk of severe hypoglycaemic episodes.
Topics: Administration, Oral; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Middle Aged; Postprandial Period; Randomized Controlled Trials as Topic; Treatment Outcome; Weight Gain
PubMed: 24471814
DOI: 10.1111/ijcp.12337 -
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 -
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 -
Diabetes, Obesity & Metabolism Nov 2013The aim of this review is to summarize the clinical efficacy, tolerability and safety data of insulin detemir, and compare its use with that of neutral protamine... (Comparative Study)
Comparative Study Review
The aim of this review is to summarize the clinical efficacy, tolerability and safety data of insulin detemir, and compare its use with that of neutral protamine Hagedorn (NPH) insulin in randomized controlled trials in people with type 1 or type 2 diabetes. A literature search was conducted with PubMed using predefined search terms. Studies were included if they met the following criteria: randomized, controlled trial, comparison of insulin detemir with NPH insulin, non-hospitalized adults aged ≥18 years with either type 1 or type 2 diabetes, and study duration of ≥12 weeks. The following types of studies were excluded: non-randomized controlled trials, studies of mixed cohorts of patients with type 1 or type 2 diabetes that did not report results separately, pharmacokinetic/pharmacodynamic studies, reviews, pooled or meta-analyses or health-economic analyses. Fourteen publications met the inclusion criteria. Nine studies in people with type 1 diabetes and three studies in people with type 2 diabetes, using insulin detemir in a basal-bolus regimen were included. Two studies were in people with type 2 diabetes using insulin detemir with oral antidiabetes medicines. In 14 studies of people with type 1 or type 2 diabetes, insulin detemir treatment provided similar or better glycaemic control, lower within-subject variability, similar or lower frequency of hypoglycaemia and less weight gain when compared with NPH insulin.
Topics: Adult; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting; Insulin, Regular, Human; Isophane Insulin, Human; Randomized Controlled Trials as Topic; Weight Gain
PubMed: 23551900
DOI: 10.1111/dom.12106 -
Expert Opinion on Pharmacotherapy Feb 2012Insulin lispro protamine suspension (ILPS) is a protamine-based insulin lispro formulation that allows 24-h coverage while limiting the number of daily injections. ILPS... (Review)
Review
INTRODUCTION
Insulin lispro protamine suspension (ILPS) is a protamine-based insulin lispro formulation that allows 24-h coverage while limiting the number of daily injections. ILPS was developed to be the basal insulin component of premixed biphasic formulations with insulin lispro, i.e., the lispro/ILPS 25/75 and 50/50 mixed compounds, but has recently also been marketed as a basal insulin analog formulation, with an indication for the therapy of diabetic patients.
AREAS COVERED
This article reviews the available literature on pharmacokinetics/pharmacodynamics (PK/PD), efficacy and safety of ILPS administered as basal insulin, or in premixed biphasic formulations, in patients with type 1 and type 2 diabetes mellitus.
EXPERT OPINION
The results of this review suggest that ILPS may be associated with a favorable time-action profile, basal and postprandial glycemic control, and efficacy in terms of rates of patients reaching glycosylated hemoglobin targets; an increased risk of hypoglycemic episodes, compared to other basal insulins, seems to be related to the percentage of patients upgrading from once- to twice-daily injections. This increased risk might be linked with the concomitant use of insulin secretagogues in patients on higher daily dosages and is generally not observed in patients using one injection of ILPS a day. Thus, ILPS can be considered a valid option both as basal insulin and as basal component of the actual premixed formulations of lispro for the therapy of diabetic patients.
Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin Lispro; Suspensions
PubMed: 22242803
DOI: 10.1517/14656566.2012.650862 -
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 -
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