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The Cochrane Database of Systematic... Sep 2015Feeding intolerance is a common clinical problem among preterm infants. It may be an early sign of necrotising enterocolitis, sepsis or other serious gastrointestinal... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Feeding intolerance is a common clinical problem among preterm infants. It may be an early sign of necrotising enterocolitis, sepsis or other serious gastrointestinal conditions, or it may result from gut immaturity with delayed passage of meconium. Glycerin laxatives stimulate passage of meconium by acting as an osmotic dehydrating agent and increasing osmotic pressure in the gut; they stimulate rectal contraction, potentially reducing the incidence of feeding intolerance.
OBJECTIVES
To assess the effectiveness and safety of glycerin laxatives (enemas/suppositories) for prevention or treatment of feeding intolerance in very low birth weight (VLBW) infants.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 4), MEDLINE, EMBASE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). We restricted our search to all randomised controlled trials and applied no language restrictions. We searched the references of identified studies and reviews on this topic and handsearched for additional articles. We searched the database maintained by the US National Institutes of Health (www.clinicaltrials.gov) and European trial registries to identify ongoing trials.
SELECTION CRITERIA
We considered only randomised or quasi-randomised controlled trials that enrolled preterm infants < 32 weeks' gestational age (GA) and/or < 1500 g birth weight. We included trials if they administered glycerin laxatives and measured at least one prespecified clinical outcome.
DATA COLLECTION AND ANALYSIS
We used standard methods of The Cochrane Collaboration and its Neonatal Group to assess methodological quality of trials, to collect data and to perform analyses.
MAIN RESULTS
We identified three trials that evaluated use of prophylactic glycerin laxatives in preterm infants. We identified no trials that evaluated therapeutic use of glycerin laxatives for feeding intolerance. Our review showed that prophylactic administration of glycerin laxatives did not reduce the time required to achieve full enteral feeds and did not influence secondary outcomes, including duration of hospital stay, mortality and weight at discharge. Prophylactic administration of glycerin laxatives resulted in failure of fewer infants to pass stool over the first 48 hours. Included trials reported no adverse events.
AUTHORS' CONCLUSIONS
Our review of available evidence for glycerin laxatives does not support the routine use of prophylactic glycerin laxatives in clinical practice. Additional studies are needed to confirm or refute the effectiveness and safety of glycerin laxatives for prevention or treatment of feeding intolerance in VLBW infants.
Topics: Enema; Enteral Nutrition; Gestational Age; Glycerol; Humans; Infant, Very Low Birth Weight; Laxatives; Meconium; Randomized Controlled Trials as Topic; Suppositories
PubMed: 26421424
DOI: 10.1002/14651858.CD010464.pub2 -
Metabolism: Clinical and Experimental Feb 2013Every year over 3.8 million people are dying of diabetes and its complications. Lifestyle intervention was suggested to have beneficial effects in preventing and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Every year over 3.8 million people are dying of diabetes and its complications. Lifestyle intervention was suggested to have beneficial effects in preventing and reducing diabetes incidence. Interventions in patients with impaired glucose tolerance (IGT), who belong to a high risk group in developing diabetes, are supposed to be especially effective. According to the evidence hierarchy, a 1a level of evidence is missing and therefore a systematic review verifying the efficacy of lifestyle intervention is needed.
MATERIALS/METHODS
Systematic review: The electronic database PubMed, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Health Technology Assessment database were searched. Main inclusion criteria were randomized controlled trials, impaired glucose tolerance, lifestyle intervention with control group and observation time >6 months. Outcome measures were all diabetes events, as defined by the authors of each study, all-cause mortality, diabetes mortality, and quality adjusted life years (QALY). Two independent reviewers abstracted the studies by title, abstract and full-text analysis. Furthermore the reporting quality of each study was assessed by using the CONSORT criteria (Consolidated Standards of Reporting Trials) and the methodological quality by SIGN 50 instrument (Scottish Intercollegiate Guidelines Network methodology checklist for randomized controlled trials). The primary outcome measure was diabetes incidence. Secondary outcome measures were overall mortality, disease-specific mortality, quality adjusted life years (QALY), and clinical parameters; body mass index (BMI), weight change, blood pressure, blood parameter, smoking, alcohol consumption.
RESULTS
7 trials which included 25 relevant publications were identified. Kappa Cohens for title-analysis were К=0.77, (CI=0.71-0.83), abstract-analysis К=0.81 (CI=0.64-0.92) and full-text analysis К=0.78 (CI=0.57-0.98). Overall 5663 patients were analyzed with primary follow-up time: India (3y), Japan (4y), Sweden (5y), Da Qing (6y), SIM (3y), DPP (5y), DPS (4y) and drop-out rate ranges from 5% to 28%. Diabetes incidence ranges from 3% to 46% in the intervention group and 9.3% to 67.7% in the control group. The India study reported ARR=16%, RRR=29% (p=0.018), Japan: ARR=6.3%, RRR=65% (p<0.001), Sweden: ARR=4%, RRR=25% (p=not significant), Da Qing: ARR=22%, RRR=32% (p<0.05), SLIM: ARR=20%, RRR=53% (p=0.025), DPP: ARR=15%, RRR=58% (significant, no p-value reported), and DPS: ARR=12%, RRR=52% (significant, no p-value reported). Mortality and morbidity were only analyzed in Da Qing study which showed no statistical differences (overall mortality: HRR 0.96, CI 0.65-1.41, CVD-mortality: HRR 0.83; CI 0.48-1.40, CVD event: HRR 0.98; CI 0.71-1.37).
CONCLUSION
Under consideration of heterogeneity in lifestyle interventions and follow up time of the included studies, this systematic review illustrated that lifestyle intervention can have a beneficial effect on the incidence of diabetes in patients with impaired glucose tolerance. However, several studies found the effect of lifestyle intervention decreased after intervention was terminated. No long-term benefit in mortality and morbidity was found. Development of standardized lifestyle intervention program is strongly needed and further long-term intervention trials using this program are crucial in evidencing the long-term efficacy.
Topics: Behavior Therapy; Diabetes Mellitus, Type 2; Glucose Intolerance; Humans; Incidence; Randomized Controlled Trials as Topic
PubMed: 22959500
DOI: 10.1016/j.metabol.2012.07.009 -
American Journal of TherapeuticsOrthostatic hypotension (OH) is a potentially debilitating condition caused by dysfunction of the autonomic nervous system, which is essential for the physiologic...
BACKGROUND
Orthostatic hypotension (OH) is a potentially debilitating condition caused by dysfunction of the autonomic nervous system, which is essential for the physiologic response to orthostatic posture. In addition to OH, autonomic dysfunction may also be associated with the development of concurrent supine hypertension (SH).
AREAS OF UNCERTAINTY
This paradoxical effect speaks to the complexity of the pathogenesis of autonomic disease and greatly complicates management of these patients. Clinicians are faced with a dilemma because aggressive treatment of orthostatic intolerance can worsen supine hypertension and attempts to control supine hypertension can worsen orthostatic intolerance.
DATA SOURCES
Systematic review of the published literature.
PREVENTION OF SUPINE HYPERTENSION
Patients should aim to avoid known stressors, perform physical maneuvers (eg, slowly getting up from bed, sleeping with head of bed elevated), manage underlying related conditions (eg, diabetes mellitus), and exercise.
MANAGEMENT OF SUPINE HYPERTENSION
With failure of conservative management, patients may advance to pharmacologic therapy. It is important to understand the underlying suspected etiology of the syndrome of supine hypertension and OH (SH-OH) to select promising pharmacologic agents. This article reviews medical treatment options to work toward achieving a better quality of life for patients afflicted with this disease. Although clonidine and beta-blockers can be used to treat hypertension without causing significant hypotension, midodrine, pyridostigmine, and droxidopa may be helpful in preventing OH.
CONCLUSION
The etiology and severity of autonomic dysfunction vary widely between patients, suggesting a need for an individualized treatment approach. Achieving perfect blood pressure control is not a realistic goal. Rather, treatment should be aimed at improving the patient's quality of life and decreasing their risk of injury and organ damage.
Topics: Droxidopa; Humans; Hypertension; Hypotension, Orthostatic; Midodrine; Quality of Life
PubMed: 31524637
DOI: 10.1097/MJT.0000000000001054 -
Alimentary Pharmacology & Therapeutics Apr 2015One-third of patients with Crohn's disease (CD) or ulcerative colitis (UC) receiving anti-TNFs do not respond to treatment, and a relevant proportion experience loss of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
One-third of patients with Crohn's disease (CD) or ulcerative colitis (UC) receiving anti-TNFs do not respond to treatment, and a relevant proportion experience loss of response or intolerance.
AIM
To investigate the efficacy and safety of a second anti-TNF agent after primary/secondary failure or intolerance to a first drug.
INCLUSION CRITERIA
studies evaluating the efficacy of infliximab (IFX), adalimumab (ADA) and certolizumab-pegol (CZP) as the second anti-TNF in CD or UC.
SEARCH STRATEGY
Bibliographical searches (PubMed/Embase).
DATA SYNTHESIS
percentage of response/remission; the meta-analysis was performed using the inverse variance method.
RESULTS
We included 46 studies (37 CD, 8 UC, 1 pouchitis). The CD studies comprised 32 switching IFX→ADA, 4 IFX→CZP and 1 ADA→IFX. Overall, the second anti-TNF after the failure of IFX in CD induced remission in 43% and response in 63% of patients. The remission rate was higher when the reason to withdraw the first anti-TNF was intolerance (61%) than after secondary (45%) or primary failure (30%); response rates were, respectively, 72%, 62% and 53%. All UC studies switched IFX→ADA, six of them reporting remission rates ranging from 0% to 50%. Adverse events rate ranged from 0% to 81% in CD, most of them mild (serious adverse event 0-21%, discontinuation rate <20%).
CONCLUSIONS
The efficacy of a second anti-TNF in CD patients largely depends on the cause for switching. The remission rate is higher when the reason to withdraw the first anti-TNF is intolerance (61%), compared with secondary (45%) or primary failure (30%). Further studies of switch ADA→IFX are needed to evaluate this strategy. PROSPERO-registry-number: CRD42014012943.
Topics: Adalimumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Certolizumab Pegol; Clinical Trials as Topic; Colitis, Ulcerative; Crohn Disease; Humans; Immunoglobulin Fab Fragments; Immunosuppressive Agents; Inflammatory Bowel Diseases; Infliximab; Middle Aged; Polyethylene Glycols; Remission Induction; Tumor Necrosis Factor-alpha
PubMed: 25652884
DOI: 10.1111/apt.13083 -
Clinical Diabetes and Endocrinology Oct 2021Gestational diabetes mellitus (GDM) is glucose intolerance first recognised during pregnancy. Both modalities and thresholds of the GDM diagnostic test, the Oral Glucose... (Review)
Review
BACKGROUND
Gestational diabetes mellitus (GDM) is glucose intolerance first recognised during pregnancy. Both modalities and thresholds of the GDM diagnostic test, the Oral Glucose Tolerance Test (OGTT), have varied widely over time and among countries. Additionally, OGTT limitations include inconsistency, poor patient tolerability, and questionable diagnostic reliability. Many biological parameters have been reported to be modified by GDM and could potentially be used as diagnostic indicators. This study aimed to 1) systematically explore biomarkers reported in the literature as differentiating GDM from healthy pregnancies 2) screen those indicators assessed against OGTT to propose OGTT alternatives.
MAIN BODY
A systematic review of GDM diagnostic indicators was performed according to PRISMA guidelines (PROSPERO registration CRD42020145499). Inclusion criteria were full-text, comprehensible English-language articles published January 2009-January 2021, where a biomarker (from blood, ultrasound, amniotic fluid, placenta) was compared between GDM and normal glucose tolerance (NGT) women from the second trimester onward to immediately postpartum. GDM diagnostic method had to be clearly specified, and the number of patients per study higher than 30 in total or 15 per group. Results were synthesised by biomarkers.
RESULTS
Of 13,133 studies identified in initial screening, 174 studies (135,801 participants) were included. One hundred and twenty-nine studies described blood analytes, one amniotic fluid analytes, 27 ultrasound features, 17 post-natal features. Among the biomarkers evaluated in exploratory studies, Adiponectin, AFABP, Betatrophin, CRP, Cystatin-C, Delta-Neutrophil Index, GGT, TNF-A were those demonstrating statistically and clinically significant differences in substantial cohorts of patients (> 500). Regarding biomarkers assessed versus OGTT (i.e. potential OGTT alternatives) most promising were Leptin > 48.5 ng/ml, Ficolin3/adiponectin ratio ≥ 1.06, Chemerin/FABP > 0.71, and Ultrasound Gestational Diabetes Score > 4. These all demonstrated sensitivity and specificity > 80% in adequate sample sizes (> / = 100).
CONCLUSIONS
Numerous biomarkers may differentiate GDM from normoglycaemic pregnancy. Given the limitations of the OGTT and the lack of a gold standard for GDM diagnosis, advanced phase studies are needed to triangulate the most promising biomarkers. Further studies are also recommended to assess the sensitivity and specificity of promising biomarkers not yet assessed against OGTT.
TRIAL REGISTRATION
PROSPERO registration number CRD42020145499.
PubMed: 34635186
DOI: 10.1186/s40842-021-00126-7 -
The Cochrane Database of Systematic... May 2012Hypertrophic cardiomyopathy (HCM) is a genetic disease with an autosomal-dominant inheritance for which negative inotropes are the most widely used initial therapies.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hypertrophic cardiomyopathy (HCM) is a genetic disease with an autosomal-dominant inheritance for which negative inotropes are the most widely used initial therapies. Observational studies and small randomised trials have suggested symptomatic and functional benefits using pacing and several theories have been put forward to explain why. Pacing, although not the primary treatment for HCM, could be beneficial to patients with relative or absolute contraindications to surgery or alcohol ablation. Several randomised controlled trials comparing pacing to other therapeutic modalities have been conducted but no Cochrane-style systematic review has been done.
OBJECTIVES
To assess the effects of pacing in drug-refractory or drug-intolerant hypertrophic cardiomyopathy patients.
SEARCH METHODS
We searched the following on the 14/4/2010: CENTRAL (The Cochrane Library 2010, Issue 1), MEDLINE OVID (from 1950 onwards ), EMBASE OVID (from 1980 onwards ), Web of Science with Conference Proceedings (from 1970 onwards). No language restrictions were applied.
SELECTION CRITERIA
Randomised controlled trials of either parallel or crossover design that assess the beneficial and harmful effects of pacing for hypertrophic cardiomyopathy were included. When crossover studies were identified, we considered data only from the first phase.
DATA COLLECTION AND ANALYSIS
Data from included studies were extracted onto a pre-formed data extraction paper by two authors independently. Data was then entered into Review Manager 5.1 for analysis. Risk of bias was assessed using the guidance provided in the Cochrane Handbook. For dichotomous data, relative risk was calculated; and for continuous data, the mean differences were calculated. Where appropriate data were available, meta-analysis was performed. Where meta-analysis was not possible, a narrative synthesis was written. A QUROUM flow chart was provided to show the flow of papers.
MAIN RESULTS
Five studies (reported in 10 papers) were identified. However, three of the five studies provided un-usable data. Thus the data from only two studies (reported in seven papers) with 105 participants were included for this review. There was insufficient data to compare results on all-cause mortality, cost effectiveness, exercise capacity, Quality of life and Peak O2 consumption.When comparing active pacing versus placebo pacing on exercise capacity, one study showed that exercise time decreased from (13.1 ± 4.4) minutes to (12.6 ± 4.3) minutes in the placebo group and increased from (12.1 ± 5.6) minutes to (12.9 ± 4.2) minutes in the treatment group (MD 0.30; 95% CI -1.54 to 2.14). Statistically significant data from the same study showed that left ventricular outflow tract obstruction decreased from (71 ± 32) mm Hg to (52 ± 34) mm Hg in the placebo group and from (70 ± 24) mm Hg to (33 ± 27) mm Hg in the active pacing group (MD -19.00; 95% CI -32.29 to -5.71). This study was also able to show that New York Heart Association (NYHA) functional class decreased from (2.5 ± 0.5) to (2.2 ± 0.6) in the inactive pacing group and decreased from (2.6 ± 0.5) to (1.7 ± 0.7) in the placebo group (MD -0.50; 95% CI -0.78 to -0.22).When comparing active pacing versus trancoronary ablation of septal hypertrophy (TASH), data from one study showed that NYHA functional class decreased from (3.2 ± 0.7) to (1.5 ± 0.5) in the TASH group and decreased from (3.0 ± 0.1) to (1.9 ± 0.6) in the pacemaker group. This study also showed that LV wall thickness remained unchanged in the active pacing group compared to reduction from (22 ± 4) mm to (17 ± 3) mm in the TASH group (MD 0.60; 95% CI -5.65 to 6.85) and that LV outflow tract obstruction decreased from (80 ± 35.5) mm Hg in the TASH group to (49.3 ± 37.7) mm Hg in the pacemaker group.
AUTHORS' CONCLUSIONS
Trials published to date lack information on clinically relevant end-points. Existing data is derived from small trials at high risk of bias, which concentrate on physiological measures. Their results are inconclusive. Further large and high quality trials with more appropriate outcomes are warranted.
Topics: Adult; Cardiomyopathy, Hypertrophic; Exercise Tolerance; Humans; Pacemaker, Artificial; Randomized Controlled Trials as Topic; Time Factors
PubMed: 22592731
DOI: 10.1002/14651858.CD008523.pub2 -
Annals of Clinical Psychiatry :... Nov 2018This systematic review evaluates current literature on anticonvulsants to treat alcohol withdrawal symptoms (AWS).
BACKGROUND
This systematic review evaluates current literature on anticonvulsants to treat alcohol withdrawal symptoms (AWS).
METHODS
We performed a literature search of PubMed, MEDLINE, PsycINFO, EMBASE, and Cochrane collaboration databases through September 30, 2016. The search was not restricted by patients' age. Articles published in English or with official English translations were included.
RESULTS
We found 16 double-blind randomized controlled trials (RCTs) that evaluated the use of anticonvulsants as treatment of AWS. Available data indicates that anticonvulsants are as effective as sedatives/hypnotics in treating mild or moderate AWS. Two studies evaluated the use of anticonvulsants as adjuncts. Combining anticonvulsants with sedatives decreases the quantity of sedatives required and AWS may resolve quicker. There is some data that anticonvulsants can be used to treat AWS as monotherapy. Fourteen of these studies assessed adverse effects of these medications; 13 studies identified minor adverse effects and one found the adverse effects to be intolerable.
CONCLUSIONS
Available evidence indicates that anticonvulsants have good efficacy as monotherapy and as adjuncts with sedatives/hypnotics in treating mild to moderate AWS.
Topics: Alcohol Withdrawal Delirium; Alcohol Withdrawal Seizures; Anticonvulsants; Benzodiazepines; Humans; Hypnotics and Sedatives
PubMed: 30372509
DOI: No ID Found -
The Cochrane Database of Systematic... Dec 2015Gestational diabetes, glucose intolerance with onset or first recognition during pregnancy, is a rising problem worldwide. Both non-pharmacological and pharmacological... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Gestational diabetes, glucose intolerance with onset or first recognition during pregnancy, is a rising problem worldwide. Both non-pharmacological and pharmacological approaches to the prevention of gestational diabetes have been, and continue to be explored. Myo-inositol, an isomer of inositol, is a naturally occurring sugar commonly found in cereals, corn, legumes and meat. It is one of the intracellular mediators of the insulin signal and correlated with insulin sensitivity in type 2 diabetes. The potential beneficial effect on improving insulin sensitivity suggests that myo-inositol may be useful for women in preventing gestational diabetes.
OBJECTIVES
To assess if antenatal dietary supplementation with myo-inositol is safe and effective, for the mother and fetus, in preventing gestational diabetes.
SEARCH METHODS
We searched the Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, WHO ICTRP (2 November 2015) and reference lists of retrieved studies.
SELECTION CRITERIA
We sought published and unpublished randomised controlled trials, including conference abstracts, assessing the effects of myo-inositol for the prevention of gestational diabetes mellitus (GDM). Quasi-randomised and cross-over trials were not eligible for inclusion, but cluster designs were eligible. Participants in the trials were pregnant women. Women with pre-existing type 1 or type 2 diabetes were excluded. Trials that compared the administration of any dose of myo-inositol, alone or in a combination preparation were eligible for inclusion. Trials that used no treatment, placebo or another intervention as the comparator were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion, risk of bias and extracted the data. Data were checked for accuracy.
MAIN RESULTS
We included four randomised controlled trials (all conducted in Italy) reporting on 567 women who were less than 11 weeks' to 24 weeks' pregnant at the start of the trials. The trials had small sample sizes and one trial only reported an interim analysis. Two trials were open-label. The overall risk of bias was unclear.For the mother, supplementation with myo-inositol was associated with a reduction in the incidence of gestational diabetes compared with control (risk ratio (RR) 0.43, 95% confidence interval (CI) 0.29 to 0.64; three trials; n = 502 women). Using GRADE methods this evidence was assessed as low with downgrading due to unclear risk of bias for allocation concealment in two of the included trials and lack of generalisability of findings. For women who received myo-inositol supplementation, the incidence of GDM ranged from 8% to 18%; for women in the control group, the incidence of GDM was 28%, using International Association of Diabetes and Pregnancy Study Groups Consensus Panel 2010 criteria to diagnose GDM.Two trials reported on hypertensive disorders of pregnancy, a primary maternal outcome of this review. There was no clear difference in risk of hypertensive disorders of pregnancy between the myo-inositol and control groups (average RR 0.43, 95% CI 0.02 to 8.41; two trials; n = 398 women; Tau(2) = 3.23; I(2) = 69%). Using GRADE methods, this evidence was assessed as very low, with downgrading due to wide confidence intervals with very low event rates, a small sample size, and lack of blinding and unclear allocation concealment methods, and a lack of generalisability. For women who received myo-inositol the risk of hypertensive disorders of pregnancy ranged from 0% to 33%; for women in the control group the risk was 4%.For the infant, none of the included trials reported on the primary neonatal outcomes of this systematic review (large-for-gestational age, perinatal mortality, mortality or morbidity composite).In terms of this review's secondary outcomes, there was no clear difference in the risk of caesarean section between the myo-inositol and control groups (RR 0.95, 95% CI 0.76 to 1.19; two trials; n = 398 women). Using GRADE methods, this evidence was assessed as low, with downgrading due to unclear risk of bias in one trial and lack of generalisability. For women who received myo-inositol supplementation, the risk of having a caesarean section ranged from 34% to 54%; for women in the control group the was 45%. There were no maternal adverse effects of therapy in the two trials that reported on this outcome (the other two trials did not report this outcome).Two trials found no clear difference in the risk of macrosomia between infants whose mothers received myo-inositol supplementation compared with controls (average RR 0.35, 95% CI 0.02 to 6.37; two trials; n = 398 infants;Tau(2) = 3.33; I(2) = 73%). Similarly, there was no clear difference between groups in terms of neonatal hypoglycaemia (RR 0.36, 95% CI 0.01 to 8.66) or shoulder dystocia (average RR 2.33, 95% CI 0.12 to 44.30, Tau(2) = 3.24; I(2) = 72%).There was a lack of data available for a large number of maternal and neonatal secondary outcomes, and no data for any of the long-term childhood or adulthood outcomes, or for health service cost outcomes.
AUTHORS' CONCLUSIONS
Evidence from four trials of antenatal dietary supplementation with myo-inositol during pregnancy shows a potential benefit for reducing the incidence of gestational diabetes. No data were reported for any of this review's primary neonatal outcomes. There were very little outcome data for the majority of this review's secondary outcomes. There is no clear evidence of a difference for macrosomia when compared with control.The current evidence is based on small trials that are not powered to detect differences in outcomes including perinatal mortality and serious infant morbidity. All of the included studies were conducted in Italy which raises concerns about the lack of generalisability of the evidence to other settings. There is evidence of inconsistency and indirectness and as a result, many of the judgements on the quality of the evidence were downgraded to low or very low quality (GRADEpro Guideline Development Tool).Further trials for this promising antenatal intervention for preventing gestational diabetes are encouraged and should include pregnant women of different ethnicities and varying risk factors and use of myo-inositol (different doses, frequency and timing of administration) in comparison with placebo, diet and exercise or pharmacological interventions. Outcomes should include potential harms including adverse effects.
Topics: Diabetes, Gestational; Female; Humans; Incidence; Inositol; Isomerism; Pregnancy; Prenatal Care; Randomized Controlled Trials as Topic
PubMed: 26678256
DOI: 10.1002/14651858.CD011507.pub2 -
The Cochrane Database of Systematic... Dec 2018Alpha-glucosidase inhibitors (AGI) reduce blood glucose levels and may thus prevent or delay type 2 diabetes mellitus (T2DM) and its associated complications in people...
Alpha-glucosidase inhibitors for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk of developing type 2 diabetes mellitus.
BACKGROUND
Alpha-glucosidase inhibitors (AGI) reduce blood glucose levels and may thus prevent or delay type 2 diabetes mellitus (T2DM) and its associated complications in people at risk of developing of T2DM.
OBJECTIVES
To assess the effects of AGI in people with impaired glucose tolerance (IGT), impaired fasting blood glucose (IFG), moderately elevated glycosylated haemoglobin A1c (HbA1c) or any combination of these.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and the reference lists of systematic reviews, articles and health technology assessment reports. The date of the last search of all databases was December 2017.
SELECTION CRITERIA
We included randomised controlled trials (RCTs), with a duration of one year or more, comparing AGI with any pharmacological glucose-lowering intervention, behaviour-changing intervention, placebo or no intervention in people with IFG, IGT, moderately elevated HbA1c or combinations of these.
DATA COLLECTION AND ANALYSIS
Two review authors read all abstracts and full-text articles or records, assessed quality and extracted outcome data independently. One review author extracted data, which were checked by a second review author. We resolved discrepancies by consensus or involvement of a third review author. For meta-analyses we used a random-effects model with assessment of risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) for effect estimates. We assessed the overall quality of the evidence by using the GRADE instrument.
MAIN RESULTS
For this update of the Cochrane Review (first published 2006, Issue 4) we included 10 RCTs (11,814 participants), eight investigating acarbose and two investigating voglibose, that included people with IGT or people "at increased risk for diabetes". The trial duration ranged from one to six years. Most trials compared AGI with placebo (N = 4) or no intervention (N = 4).Acarbose reduced the incidence of T2DM compared to placebo: 670 out of 4014 people (16.7%) in the acarbose groups developed T2DM, compared to 812 out of 3994 people (20.3%) in the placebo groups (RR 0.82, 95% CI 0.75 to 0.89; P < 0.0001; 3 trials; 8008 participants; moderate-certainty evidence). One trial including participants with coronary heart disease and IGT contributed 64% of cases for this outcome. Acarbose reduced the risk of T2DM compared to no intervention: 7 out 75 people (9.3%) in the acarbose groups developed T2DM, compared to 18 out of 65 people (27.7%) in the no-intervention groups (RR 0.31, 95% CI 0.14 to 0.69; P = 0.004; 2 trials; 140 participants; very low-certainty evidence).Acarbose compared to placebo did not reduce or increase the risk of all-cause mortality (RR 0.98, 95% CI 0.82 to 1.18; P = 0.86; 3 trials; 8069 participants; very low-certainty evidence), cardiovascular mortality (RR 0.88; 95% CI 0.71 to 1.10; P = 0.26; 3 trials; 8069 participants; very low-certainty evidence), serious adverse events (RR 1.12, 95% CI 0.97 to 1.29; P = 0.13; 2 trials; 6625 participants; low-certainty evidence), non-fatal stroke (RR 0.50, 95% CI 0.09 to 2.74; P = 0.43; 1 trial; 1368 participants; very low-certainty evidence) or congestive heart failure (RR of 0.87; 95% CI 0.63 to 1.12; P = 0.40; 2 trials; 7890 participants; low-certainty evidence). Acarbose compared to placebo reduced non-fatal myocardial infarction: one out of 742 participants (0.1%) in the acarbose groups had a non-fatal myocardial infarction compared to 15 out of 744 participants (2%) in the placebo groups (RR 0.10, 95% CI 0.02 to 0.53; P = 0.007; 2 trials; 1486 participants; very low-certainty evidence). Acarbose treatment showed an increased risk of non-serious adverse events (mainly gastro-intestinal events), compared to placebo: 751 of 775 people (96.9%) in the acarbose groups experienced an event, compared to 723 of 775 people (93.3%) in the placebo groups (RR 1.04; 95% CI 1.01 to 1.06; P = 0.0008; 2 trials; 1550 participants). Acarbose compared to no intervention showed no advantage or disadvantage for any of these outcome measures (very low-certainty evidence).One trial each compared voglibose with placebo (1780 participants) or diet and exercise (870 participants). Voglibose compared to placebo reduced the incidence of T2DM: 50 out of 897 participants (5.6%) developed T2DM, compared to 106 out of 881 participants (12%) in the placebo group (RR 0.46, 95% CI 0.34 to 0.64; P < 0.0001; 1 trial; 1778 participants; low-certainty evidence). For all other reported outcome measures there were no clear differences between voglibose and comparator groups. One trial with 90 participants compared acarbose with diet and exercise and another trial with 98 participants reported data on acarbose versus metformin. There were no clear differences for any outcome measure between these two acarbose interventions and the associated comparator groups.None of the trials reported amputation of lower extremity, blindness or severe vision loss, end-stage renal disease, health-related quality of life, time to progression to T2DM, or socioeconomic effects.
AUTHORS' CONCLUSIONS
AGI may prevent or delay the development of T2DM in people with IGT. There is no firm evidence that AGI have a beneficial effect on cardiovascular mortality or cardiovascular events.
Topics: Acarbose; Blood Glucose; Cause of Death; Diabetes Mellitus, Type 2; Diet; Exercise; Fasting; Glucose Intolerance; Glycoside Hydrolase Inhibitors; Humans; Incidence; Inositol; Metformin; Prediabetic State; Randomized Controlled Trials as Topic
PubMed: 30592787
DOI: 10.1002/14651858.CD005061.pub3