Datasets:

marianna13
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litarch

+{"file": "rc0693_NBK315876/CH5.nxml", "text": "Quantity of Research Available\nA total of 238 citations were identified in the literature search. Following screening of titles and abstracts, 224 citations were excluded and 14 potentially relevant reports from the electronic search were retrieved for full-text review. One potentially relevant publication was retrieved from the grey literature search. Of these 15 potentially relevant articles, 11 publications were excluded. Of these 11, five publications were excluded because the population did not fit the age restrictions,21\u201325 one was excluded due to an inappropriate intervention,26 four were excluded due to inappropriate comparators,27\u201330 and one was excluded due to insufficient review methodology.7 Four publications met the inclusion criteria and were included in this report.31\u201334 The PRISMA flowchart of the study selection is presented in Appendix 1.\nAdditional references of potential interest are provided in Appendix 5.\nSummary of Study Characteristics\nDetailed study characteristics are listed in Appendix 2.\nStudy Design\nFour non-randomized studies regarding the safety of glyburide, gliclazide or glimepiride in elderly patients with type 2 diabetes were identified. All included studies utilized administrative health records or hospital databases to collect health information. This included three retrospective cohort studies,31, 32, 34 and one nested case control study.33\nCountry of Origin\nThe included studies were conducted in Canada,31, 33, 34 and South Korea.32 Two of the Canadian studies used Alberta administrative health data,31, 33 and one used data from Ontario.34\nPatient Population\nPatient populations included elderly individuals (aged 60 and over) with diagnosed type 2 diabetes who were treated with the medications of interest.31\u201334 Baseline glycated hemoglobin levels were not reported by most studies31, 33, 34 with the exception of Lee et al., who reported that over 65% of patients had baseline levels greater than 7%. In some cases other comorbidities were part of the inclusion criteria, including ischemic heart disease,31 and coronary artery disease.34\nInterventions and Comparators\nInterventions included glyburide, gliclazide, and glimepiride. Comparators could include any alternate sulfonylurea, including those not previously listed, but were primarily limited to the three drugs. One study31 included an additional comparison to repaglinide.\nOutcomes\nNo efficacy outcomes were assessed by any of the studies. Adverse event outcomes included cardiovascular adverse events and associated hospitalizations and/or death,31, 33, 34 and renal endpoints.32 In addition, secondary outcomes such as pneumonia33, 34 and hemorrhage34 were recorded.\nSummary of Critical Appraisal\nA detailed list of critical appraisal points based on the Downs and Black20 checklist is available in Appendix 3.\nOverall, the study information was well reported apart from lacking adverse event profiles. Use of database and administrative health information resulted in good generalizability in most cases, with minor issues related to the reach and size of the databases. Internal validity was limited by the lack of blinding and randomization leading to possible selection and performance bias, as well as the possibility of outcome misclassification bias inherent to database studies. In addition, incomplete consideration of confounders and post-hoc propensity score analysis may have led to under-adjustment of associations. Power was generally poorly reported.\nReporting\nA well stated hypothesis or objective was provided for all studies.31\u201334 The main outcomes to be assessed were described in the introduction or methods section of the studies.31\u201334 The characteristics of patients and interventions, main findings, and confounder distribution were clearly described.31\u201334 All studies provided estimates of random variability for the main outcomes listed and probability values and confidence intervals were provided where appropriate.31\u201334 Due to the use of administrative health data and healthcare databases there were no apparent losses to follow up, apart from censoring 30 days post index date by one study,31 and the exclusion of individuals with a dual drug history in another.32 However, potential unrecorded records or excluded records were not discussed. The main flaw in reporting was the limited adverse event profile. All studies focused primarily on the main outcome and failed to report on common adverse events associated with the use of the interventions such as hypoglycemia, falls, weight gain and gastrointestinal side-effects.31\u201334\nExternal Validity\nBased on the use of administrative health data, the participants were representative of the population from which they were drawn. In the case of two studies population health information was used.31, 34 so the generalizability was relatively wide, versus the use of private health plan data33 and single hospital data from a diabetes care center32 by the other two studies, which may have excluded some relevant participants. The use of previously collected data precluded any issues regarding differences in willing and unwilling participants. Again, population-based data likely resulted in generalizable facilities, staff and setting of treatment; however, in the case of the diabetes center patients may have had access to more specialized care.32 The majority of studies were conducted using administrative health records and health databases collected in the Canadian setting,31, 33, 34 increasing the generalizability to Canadian clinical practice and populations.\nInternal Validity \u2013 Bias\nNone of the studies instituted blinding methods for participants or outcome assessors. Three of the studies adjusted for length of follow-up via the use of survival analysis.31, 32, 34 One study failed to adjust for length of follow-up in multivariate models.33 In general, appropriate statistical tests were used and the main outcome measures were accurate, although there is always the possibility of misclassification of outcomes and reporting bias with the use of database information. It was unclear whether the subgroup and sensitivity analyses were preplanned in three cases,31\u201333 and one study did not perform subgroup analysis.34 Compliance with the study interventions was unclear in all cases; therefore, whether dispensation of medication led to treatment was uncertain.\nInternal Validity \u2013 Confounding\nNo randomization of study subjects was completed for any of the studies;31\u201334 therefore, only associations between second generation sulfonylurea use and safety outcomes could be explored. Patients in the comparison groups were recruited over the same time period, from the same population pool for all studies. Two studies used propensity scoring to pre-match individuals in the comparison groups,32, 34 while two conducted post-hoc propensity score adjusted analysis.31, 34 In multivariate analysis, all studies considered potential confounders; however, in all cases the included confounders did not necessarily represent all potential confounders.\nPower\nOne study32 reported a power calculation, but did not discuss whether they enrolled enough subjects to achieve sufficient power to detect the primary outcome. The other studies failed to disclose a power calculation or discuss the power to detect clinically important differences in their main outcomes.\nSummary of Findings\nDetailed study findings are tabulated in Appendix 4.\nWhat is the comparative clinical effectiveness of glyburide versus gliclazide or glimepiride in elderly patients with type 2 diabetes?\nNo relevant evidence was identified regarding the comparative clinical effectiveness of glyburide versus gliclazide or glimepiride in elderly patients with type 2 diabetes; therefore, no summary can be provided.\nWhat is the clinical evidence regarding the safety of glyburide, gliclazide or glimepiride in elderly patients with type 2 diabetes?\nCardiovascular Outcomes\nThere was disagreement among the three studies31, 33, 34 that assessed individual and composite cardiovascular outcomes. One retrospective cohort study31 reported no difference in the risk of progression to a composite outcome of all-cause mortality, new onset of atrial fibrillation, stroke, heart failure, or myocardial infarction within 30 days of the index date between gliclazide and glyburide users. As well, each individual outcome analyzed separately showed no difference in the risk of progression between the gliclazide and glyburide groups.31 One nested case-control study33 reported increased odds of acute coronary syndrome related hospitalization or death, with a corresponding number needed to harm of 50 for treatment with glyburide versus gliclazide. When the composite outcome was analyzed separately, only hospitalization due to acute coronary syndrome was significantly associated with glyburide use. The other retrospective cohort study34 observed no difference in the risk of progression towards a composite outcome of death or hospitalization due to acute myocardial infarction or heart failure after index hospitalization between glyburide and gliclazide users. When analyzed separately, risk of progression to individual components of the composite outcome were also similar between groups.34 There was no data available on the cardiovascular adverse events associated with glimepiride.\nRenal Outcomes\nOne retrospective cohort study concluded that glimepiride was associated with an increased risk of progression to end stage renal disease and a doubling of serum creatinine to at least 132.6 \u03bcmol/L in patients aged 62 and older versus gliclazide. No data was available on the renal adverse events associated with glyburide.\nSecondary Outcomes\nNo differences in the odds of pneumonia33 or risk of progression to pneumonia or hemorrhage34 were observed between treatment groups for the two studies that assessed tracer outcomes.\nLimitations\nThe use of databases and administrative health data posed several limitations. Firstly, the studies did not report on treatment compliance, which is hard to monitor retrospectively. Dispensation of medication may not perfectly correlate with use and this could increase the risk of exposure misclassification, and thus could result in over-estimation of the risk of medication use. In addition, the two studies that used non-population based databases32, 33 may have restricted analysis to patients who were able to access specialized diabetes care,32 or those who initiated access to government-sponsored private health coverage.33 In the latter case, the Alberta government fully subsidizes the coverage that Alberta Blue Cross provides, but some individuals may choose not to enroll.33 These study populations may represent individuals with greater health seeking behaviors, which could lead to an underestimation of the adverse effects of these medications. The lack of information regarding validation of the various databases that were used suggests the potential for outcome misclassification. For example, if medications were used to ascertain disease state, reason for hospitalization was not correctly coded, or the cause of death was attributed to an acute condition rather than underlying disease then this may have influenced patient classification.\nThere was general underreporting of adverse events, given the well-known outcomes associated with the use of sulfonylureas. In particular, hypoglycemia, weight gain, falls and other hypoglycemia related sequelae, and gastrointestinal outcomes may have been of interest and may have influenced multivariate analysis.\nSome of the studies assessed composite cardiovascular outcomes.31, 33, 34 One study33 reported divergence in the results for the composite outcome and that of the individual outcomes. This could have resulted for multiple reasons including a lack of power to detect clinically meaningful differences in the individual outcomes (hospitalization and death), or a true lack of risk of progression to death. As such, these results should be interpreted with caution.\nOne study34 included patients with a history of the primary outcome in analysis. In this case it was unclear whether treatment exposure occurred prior to the onset of cardiovascular symptoms, which could have resulted in some outcomes being wrongly attributed to exposure.\nLastly, because this review focused on elderly populations, there may be reports on the adverse effects associated with the use of various sulfonylureas in study populations with wider age ranges (e.g., all adults 18 years and older) that were not reviewed. This includes reports on hypoglycemia, mortality, cancer, and weight gain. While the findings of these reports may not be applicable to elderly individuals, and would therefore be considered out of scope, they may be of wider interest and are listed in Appendix 5. The lack of information on these outcomes within this report does not suggest an absence of risk. Rather, there is a lack of evidence available on these outcomes in elderly persons.", "pairs": [], "interleaved": []}
+{"file": "rc0693_NBK315876/CH3.nxml", "text": "Limited evidence from four non-randomized studies suggests an increased risk of progression towards adverse renal endpoints with the use of glimepiride versus gliclazide, as well as conflicting results regarding the risk of progression to cardiovascular endpoints with the use of glyburide versus gliclazide in elderly patients. This indicates a need for further high quality prospective research on this topic. No recent evidence was identified regarding the comparative clinical effectiveness of second-generation sulfonylureas.", "pairs": [], "interleaved": []}
+{"file": "rc0693_NBK315876/CH2.nxml", "text": "\nWhat is the comparative clinical effectiveness of glyburide versus gliclazide or glimepiride in elderly patients with type 2 diabetes?What is the clinical evidence regarding the safety of glyburide, gliclazide or glimepiride in elderly patients with type 2 diabetes?\nWhat is the comparative clinical effectiveness of glyburide versus gliclazide or glimepiride in elderly patients with type 2 diabetes?\nWhat is the clinical evidence regarding the safety of glyburide, gliclazide or glimepiride in elderly patients with type 2 diabetes?", "pairs": [], "interleaved": []}
+{"file": "rc0693_NBK315876/CH6.nxml", "text": "Four non-randomized studies were identified regarding the safety of glyburide, gliclazide or glimepiride in elderly patients with type 2 diabetes. Results from one study indicated potential renal risks for elderly patients using glimepiride versus gliclazide,32 while three studies assessing cardiovascular outcomes were collectively inconclusive with regards to cardiovascular morbidity and mortality associated with glyburide versus gliclazide use.31, 33, 34 Two retrospective cohort studies reported no differences between glyburide and gliclazide,31, 34 while one nested case-control study reported a small increased risk of progression towards cardiovascular outcomes with glyburide use, consistent with recent perceived risks associated with the use of this medication.12, 18 No studies compared the efficacy or safety of glimepiride and glyburide.\nThis report builds on a previous CADTH review conducted in 2011, which concluded, based on the two non-randomized studies identified, that there was a paucity of evidence regarding both the comparative efficacy and safety of glyburide, gliclazide and glimepiride.17 Further, the available safety data was inconclusive, with a single study reported an increased risk of all-cause mortality for glyburide users relative to gliclazide users. While hypoglycemia was not explored by this review, a non-systematic review article7 and an earlier systematic review are also available on the topic and provide evidence to suggest that glyburide is associated with an increased risk of severe hypoglycemia35 compared to other second generation sulfonylureas, especially in the elderly and should not be used in individuals over the age of 60.7, 35 Clinical practice guidelines from the Canadian Diabetes Association state that gliclazide and glimepiride are preferred for the elderly due to a lower frequency of hypoglycemia and cardiovascular events. 36\nDue to the lack of head-to-head data from randomized controlled trials on the various sulfonylureas, network meta-analysis has been conducted to explore indirect comparisons.23 However, none of these analyses focus on elderly populations. Given that the evidence from well-conducted non-randomized studies is limited and conflicting, indirect comparisons involving data on the elderly or well-designed prospective studies are needed to resolve disagreement. No evidence was identified on the comparative clinical effectiveness of the agents of interest; however, this topic has been explored in depth by earlier publications that suggest equivalent effectiveness of the various agents.37\nIn conclusion, limited evidence suggests a potential association between both renal and cardiovascular events and the use of certain second-generation sulfonylureas. However; assessed collectively, the evidence is conflicting and inconclusive. The limitations of non-randomized studies and the absence of comprehensive adverse event monitoring should be considered in interpretation of these results.", "pairs": [], "interleaved": []}
+{"file": "rc0693_NBK315876/CH1.nxml", "text": "Almost two million Canadians (6.5% of the total population) aged 12 and older were reported to have diabetes in 2012, making it the seventh leading cause of death.1, 2 In 2010 the cost of diabetes was estimated at 12 billion in Canada.2 Type 2 diabetes is the most prevalent form of diabetes comprising approximately 90 to 95% of total cases. It is characterized by persistent hyperglycemia caused by insulin resistance and/or decreased insulin production, which results in micro and macro-vascular complications. It is associated with lifestyle factors (body mass index, physician activity, and tobacco use), genetic factors, ethnicity, socioeconomic status3 and increasing age,4\u20136 and common associated health outcomes include renal failure, ocular morbidities, and risk of amputation due to diabetic ulcers.7\nElderly patients with type 2 diabetes exist along a spectrum, which ranges from healthy community dwelling individuals, to frail elderly living in nursing homes and hospitals with significant comorbidities.5 Physiological changes associated with aging such as reduced hepatic and renal function, comorbidities (e.g., cardiovascular disease, osteoarthritis), and polypharmacy may increase the risk and severity of adverse outcomes associated with the treatment of diabetes, including hypoglycemia, hypotension, other cardiovascular events, and adverse drug interactions.8 Therapeutic goals for all older persons, particularly frail elderly, may not reflect the same standard as younger patients and more conservative glycated hemoglobin (HbA1c) targets have been proposed for individuals with comorbidities and reduced life expectancy.5, 9\nSulfonylureas are a class of glucose lowering drugs used to treat type 2 diabetes. These drugs bind to sulfonylurea receptors and stimulate closure of adenosine triphosphate sensitive potassium channels to encourage insulin secretion from pancreatic beta cells.10, 11 Glyburide (also referred to as glibenclamide), gliclazide, and glimepiride are three second-generation sulfonylurea drugs available in Canada. Glyburide has been associated with an increased risk for hypoglycemia and long-term cardiovascular mortality.12 This may be due to differences in tissue-specific binding of the respective sulfonylureas.12 A meta-analysis published in 2007 reported an increased risk of hypoglycemia for glyburide compared to other insulin secreting anti-diabetes drugs and alternate sulfonylureas, despite no evidence of improved efficacy.10 Hypoglycemia can lead to undesirable outcomes including altered mental status, seizures, coma and death.13\u201315 It is more strongly associated with the use of long-acting sulfonylureas (e.g., glyburide and glimepiride) than short-acting sulfonylureas (e.g., gliclazide).5 The American Geriatrics Society\u2019s Beers Criteria lists a strong recommendation based on high quality evidence that glyburide be avoided in the elderly due to the potential risks.16 Based on US market pricing, gliclazide is three times higher in price than glyburide, which may contribute to the persistent use of glyburide.7\nA previous CADTH review17 of literature published from 2007 to 2011 reported that there was no evidence regarding the comparative clinical effectiveness of these agents in the elderly, and limited evidence regarding safety, based on the results of two non-randomized studies. One included study reported greater all-cause mortality associated with glyburide use versus gliclazide, and the other reported a numerically higher occurrence of hypoglycemia among patients taking glyburide monotherapy.17 Thus far, only limited evidence regarding the comparative effects of these drugs in the elderly has been synthesized and recent concerns regarding the cardiovascular effects of these drugs have been noted.18 Thus, this update will expand on the work of the previous CADTH reports17, 19 to further investigate the comparative clinical efficacy and safety of these medications in older persons.", "pairs": [], "interleaved": []}
+{"file": "rc0693_NBK315876/APP1.nxml", "text": "\n\n", "pairs": [], "interleaved": []}