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The Cochrane Database of Systematic... Oct 2019Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists are insulin-sensitising drugs used for the treatment of insulin resistance. In addition to lowering... (Review)
Review
BACKGROUND
Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists are insulin-sensitising drugs used for the treatment of insulin resistance. In addition to lowering glucose in diabetes, these drugs may also protect against hyperlipidaemia and arteriosclerosis, which are risk factors for stroke. This is an update of a review first published in January 2014 and subsequently updated in December 2017.
OBJECTIVES
To assess the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events for people with stroke or transient ischaemic attack (TIA).
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (30 July 2019), the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 7), MEDLINE (1949 to 30 July 2019), Embase (1980 to 30 July 2019), CINAHL (1982 to 30 July 2019), AMED (1985 to 30 July 2019), and 11 Chinese databases (30 July 2019). In an effort to identify further published, unpublished, and ongoing trials, we searched ongoing trials registers, reference lists, and relevant conference proceedings, and contacted authors and pharmaceutical companies. We did not impose any language restrictions.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) evaluating PPAR-γ agonists versus placebo for the secondary prevention of stroke and related vascular events in people with stroke or TIA, with the outcomes of recurrent stroke, vascular events, and adverse events.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted eligible data, cross-checked the data for accuracy, and assessed methodological quality and risk of bias. We evaluated the quality of evidence for each outcome using the GRADE approach.
MAIN RESULTS
We identified five RCTs with 5039 participants; two studies had a low risk of bias for all domains. Four studies evaluated the drug pioglitazone, and one study evaluated rosiglitazone. The participants in different studies were heterogeneous.Recurrent strokeThree studies evaluated the number of participants with recurrent stroke (4979 participants, a single study contributing 3876 of these). Peroxisome proliferator-activated receptor gamma agonists probably reduce the recurrence of stroke compared with placebo (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.44 to 0.99; moderate-quality evidence).Adverse eventsEvidence that adverse events occurred more frequently in participants treated with PPAR-γ agonists when compared with placebo was uncertain due to wide confidence interval and high levels of statistical heterogeneity: risk difference 10%, 95% CI -8% to 28%; low-quality evidence).Data were available on additional composite outcomes reflecting serious vascular events (all-cause death and other major vascular events; all-cause mortality, non-fatal myocardial infarction or non-fatal stroke) from one study in 984 people. This study provided low-quality evidence that PPAR-γ agonists led to fewer events (data not meta-analysed).Vascular eventsPeroxisome proliferator-activated receptor gamma agonists given over a mean duration of 34.5 months in a single trial of 984 participants may reduce serious vascular events expressed as a composite outcome of total events of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke (RR 0.73, 95% CI 0.54 to 0.99; low-quality evidence).Other outcomesOne study in 20 people measured insulin sensitivity, and one study in 40 people measured the ubiquitin-proteasome activity in carotid plaques. Our confidence in the improvements observed with PPAR-γ agonists were limited by small sample sizes and risk of bias. None of the studies reported the number of participants with disability due to vascular events or improvement in quality of life.
AUTHORS' CONCLUSIONS
Peroxisome proliferator-activated receptor gamma agonists probably reduce recurrent stroke and total events of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke, and may improve insulin sensitivity and the stabilisation of carotid plaques. Their effects on adverse events are uncertain. Our conclusions should be interpreted with caution considering the small number and the quality of the included studies. Further well-designed, double-blind RCTs with large samples are required to assess the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events in people with stroke or TIA.
PubMed: 31596946
DOI: 10.1002/14651858.CD010693.pub5 -
Saudi Medical Journal Jun 2019Non-alcoholic fatty liver disease (NAFLD) is a major national and international health burden. It is one of the most common liver diseases worldwide and the most common...
Non-alcoholic fatty liver disease (NAFLD) is a major national and international health burden. It is one of the most common liver diseases worldwide and the most common cause of abnormal liver enzymes in many developed countries. Non-alcoholic fatty liver disease is also known as an important cause of cryptogenic cirrhosis and second leading cause for liver transplantation. It is commonly associated with metabolic syndrome. Non-alcoholic steatohepatitis (NASH) is the progressive phenotype of NAFLD. In spite of promising performance of non-invasive tools, liver biopsy remains the gold standard test for NASH diagnosis. Over decades, many drugs have been investigated in phase 2 and 3; however, no approved therapy to date. Despite the alarming global rates of NAFLD, there are no local community-based studies on the prevalence of NAFLD or local practice guidelines on its management; this expert review aims to fill this gap.
Topics: Bariatric Surgery; Biomarkers; Biopsy; Chalcones; Chenodeoxycholic Acid; Diagnostic Imaging; Healthy Lifestyle; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Insulin; Liver; Liver Transplantation; Mass Screening; Non-alcoholic Fatty Liver Disease; Pioglitazone; Prevalence; Propionates; Thiazolidinediones; Vitamin E
PubMed: 31219486
DOI: 10.15537/smj.2019.6.23980 -
Anti-Inflammatory Treatments for Depression: Perspectives on How to Read a Meta-Analysis Critically.The Journal of Clinical Psychiatry May 2019Inflammatory mechanisms have been implicated in many psychiatric disorders, including depression, and anti-inflammatory agents have been suggested as potential... (Meta-Analysis)
Meta-Analysis
Inflammatory mechanisms have been implicated in many psychiatric disorders, including depression, and anti-inflammatory agents have been suggested as potential treatments. In this context, a systematic review and meta-analysis of nonsteroidal anti-inflammatory drugs, cytokine inhibitors, glucocorticoids, statins, minocycline, and pioglitazone, all of which are considered to have anti-inflammatory properties, examined the antidepressant benefits of these agents in 36 randomized controlled trials conducted in patients with major depressive disorder (MDD) and patients with medical diseases and associated depressive symptoms. The meta-analysis found that, overall, relative to placebo, these drugs had superior antidepressant effect in patients with MDD as well as in those with medical disease. With the exception of pioglitazone, every drug/category also outperformed placebo. However, the findings of this extensive meta-analysis do not guide theory; because the different anti-inflammatory agents studied have multiple pharmacodynamic actions, there is no assurance that their anti-inflammatory mechanism was responsible for the reported antidepressant benefits. The findings do not guide clinical practice, either, because of substantial clinical and statistical heterogeneity; no specific drug, dose, duration of treatment, and disorder were identified for application of the findings. Finally, the meta-analysis contained obvious and non-obvious errors, including the combination of endpoint and improvement scores in the same summary estimate (standardized mean deviation) and the use of percentage scores rather than absolute scores in the computations. These issues are explained so that readers can more easily consider or detect the limitations of meta-analyses that are published.
Topics: Adolescent; Anti-Inflammatory Agents; Antidepressive Agents; Comorbidity; Depressive Disorder, Major; Female; Humans; Male; Randomized Controlled Trials as Topic; Treatment Outcome; Young Adult
PubMed: 31120202
DOI: 10.4088/JCP.19f12907 -
Scientific Reports Mar 2019Pioglitazone, the only thiazolidinedione drug in clinical practice is under scrutiny due to reported adverse effects, it's unique insulin sensitising action provides... (Meta-Analysis)
Meta-Analysis
Pioglitazone, the only thiazolidinedione drug in clinical practice is under scrutiny due to reported adverse effects, it's unique insulin sensitising action provides rationale to remain as a therapeutic option for managing type 2 diabetes mellitus (T2DM). We conducted a systematic review and meta-analysis comparing pioglitazone monotherapy with monotherapies of other oral antidiabetic drugs for assessing its efficacy and safety in T2DM patients. Mean changes in glycated haemoglobin (HbA1c), and mean changes in fasting blood sugar (FBS) level, body weight (BW) and homeostasis model assessment-insulin resistance (HOMA-IR) were primary and secondary outcomes, respectively. Safety outcomes were changes in lipid parameters, blood pressure and incidences of adverse events. Metafor package of R software and RevMan software based on random-effects model were used for analyses. We included 16 randomised controlled trials. Pioglitazone monotherapy showed equivalent efficacy as comparators in reducing HbA1c by 0.05% (95% CI: -0.21 to 0.11) and greater efficacy in reducing FBS level by 0.24 mmol/l (95% CI: -0.48 to -0.01). Pioglitazone showed similar efficacy as comparators in reducing HOMA-IR (WMD: 0.05, 95% CI: -0.49 to 0.59) and increasing high-density lipoprotein level (WMD: 0.02 mmol/l, 95% CI: -0.06 to 0.10). Improved blood pressure (WMD: -1.05 mmHg, 95% CI: -4.29 to 2.19) and triglycerides level (WMD: -0.71 mmol/l, 95% CI: -1.70 to 0.28) were also observed with pioglitazone monotherapy. There was a significant association of pioglitazone with increased BW (WMD: 2.06 kg, 95% CI: 1.11 to 3.01) and risk of oedema (RR: 2.21, 95% CI: 1.48 to 3.31), though the risk of hypoglycaemia was absolutely lower (RR: 0.51, 95% CI: 0.33 to 0.80). Meta-analysis supported pioglitazone as an effective treatment option for T2DM patients to ameliorate hyperglycaemia, adverse lipid metabolism and blood pressure. Pioglitazone is suggested to prescribe following individual patient's needs. It can be a choice of drug for insulin resistant T2DM patients having dyslipidaemia, hypertension or history of cardiovascular disease.
Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Pioglitazone
PubMed: 30926892
DOI: 10.1038/s41598-019-41854-2 -
Endocrinology, Diabetes & Metabolism Jan 2019To evaluate the efficacy and safety of combined therapy with sodium-glucose cotransporter 2 (SGLT-2) inhibitors plus pioglitazone versus pioglitazone alone in type 2...
Sodium-glucose cotransporter 2 inhibitor plus pioglitazone vs pioglitazone alone in patients with diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials.
AIMS
To evaluate the efficacy and safety of combined therapy with sodium-glucose cotransporter 2 (SGLT-2) inhibitors plus pioglitazone versus pioglitazone alone in type 2 diabetic patients.
MATERIALS AND METHODS
Systematic literature searches were performed across PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and clinicaltrials.gov from 1966 to September 2018 to identify randomized, controlled trials. Mean difference (MD) or odds ratio (OR) was used to evaluate efficacy and safety end-points (active group vs control group), wherever appropriate. Heterogeneity was assessed by value of χ statistics and .
RESULTS
Four randomized controlled trials with 1411 diabetic patients were included. Pooling data from included trials showed that HbA1c change was significantly larger in both low-dose SGLT-2 inhibitors (MD: -0.59%, 95% CI: -0.77 to -0.41%) and high-dose SGLT-2 inhibitors (MD: -0.65%, 95% CI: -0.78 to -0.53%) plus pioglitazone than pioglitazone alone in 24-26 weeks. Favourable outcomes were also found in fasting blood glucose level reduction and more patients achieving HbA1c <7% in SGLT-2 inhibitor plus pioglitazone (OR: 3.21, 95% CI: 1.99 to 5.16). Also, SGLT-2 inhibitor plus pioglitazone vs pioglitazone, reduced weight and blood pressure. The risks of death, heart failure, hypoglycaemia and urinary tract infection were not different between active and control groups although genital tract infection was more frequently seen in SGLT-2 inhibitor group.
CONCLUSIONS
Compared to pioglitazone alone, SGLT-2 inhibitor plus pioglitazone improved glycaemic control, reduced body weight and lowered blood pressure, but increased genital tract infection.
PubMed: 30815577
DOI: 10.1002/edm2.50 -
Diabetology International Jan 2019Studies investigating bladder cancer risk in pioglitazone-treated type 2 diabetes mellitus patients report conflicting results. Previous meta-analyses on this topic...
BACKGROUND
Studies investigating bladder cancer risk in pioglitazone-treated type 2 diabetes mellitus patients report conflicting results. Previous meta-analyses on this topic utilized publications prior to 2013. More long-term observational studies have been published since then. We reviewed the accumulated evidence and updated findings from previous meta-analyses.
METHODS
This meta-analysis was based on a systematic review of peer-reviewed observational studies published prior to September 30, 2016. Eligible studies were identified using a specified MEDLINE search. References from included studies and from previous meta-analyses were screened for additional records. Meta-analysis hazards ratios were derived using a random-effects model. Several sensitivity analyses including hierarchical Bayesian meta-analysis with country-specific effects were conducted.
RESULTS
Of 363 identified records, 23 studies were included in this review and 18 in the actual meta-analyses. For bladder cancer outcome, the estimated effect size for ever vs. never use of pioglitazone was 1.16 [95% confidence interval (CI), 1.04-1.28]. In the cumulative dose and duration analyses, highest effect was observed in the highest/longest exposure group, but substantial heterogeneity was present. In the sensitivity analysis, only studies adjusted for lifestyle-related factors were included and the frequentist effect size was 1.18 (95% CI, 1.00-1.40, = 0.054). However, the risk was not verified in the Bayesian framework with an effect size of 1.17 [95% credible interval (CrI), 0.94-1.54].
CONCLUSIONS
In line with previous meta-analyses, we observed a small but statistically significant association between ever (vs. never) use of pioglitazone and bladder cancer risk; however, causality is not established and alternative explanations cannot be ruled out.
PubMed: 30800561
DOI: 10.1007/s13340-018-0360-4 -
World Journal of Diabetes Feb 2019Non-alcoholic fatty liver disease (NAFLD) is a common comorbidity with type 2 diabetes. The existing therapeutic options for NAFLD are not adequate. Hypocaloric diet and...
BACKGROUND
Non-alcoholic fatty liver disease (NAFLD) is a common comorbidity with type 2 diabetes. The existing therapeutic options for NAFLD are not adequate. Hypocaloric diet and exercise is the cornerstone of therapy in NAFLD. Pioglitazone is the only drug recommended in diabetes patients with biopsy proven non-alcoholic steatohepatitis. The frequent coexistence of NAFLD and type 2 diabetes with their combined adverse health consequences and inadequate therapeutic options makes it necessary to search for newer alternatives.
AIM
To assess the effect of sodium glucose cotransporter-2 (SGLT-2) inhibitors on liver enzymes in type 2 diabetes patients with NAFLD.
METHODS
We searched PubMed/MEDLINE, Cochrane library, Google scholar, and Clinicaltrials.gov for the relevant articles to be included in this systematic review. Human studies done in type 2 diabetes patients with NAFLD treated with SGLT-2 inhibitors for at least 12 wk were included. Data from eight studies (four randomised controlled trials and four observational studies) were extracted and a narrative synthesis was done. A total of 214 patients were treated with SGLT-2 inhibitors in these studies (94 in randomised controlled trials and 120 in observational studies).
RESULTS
The primary outcome measure was change in serum alanine aminotransferase level. Out of eight studies, seven studies showed a significant decrease in serum alanine aminotransferase level. Most of the studies revealed reduction in serum level of other liver enzymes like aspartate aminotransferase and gamma glutamyl transferase. Five studies that reported a change in hepatic fat exhibited a significant reduction in hepatic fat content in those treated with SGLT-2 inhibitors. Likewise, among the three studies that evaluated a change in indices of hepatic fibrosis, two studies revealed a significant improvement in liver fibrosis. Moreover, there was an improvement in obesity, insulin resistance, glycaemia, and lipid parameters in those subjects taking SGLT-2 inhibitors. The studies disclosed that about 17% (30/176) of the subjects taking SGLT-2 inhibitors developed adverse events and more than 40% (10/23) of them had genitourinary tract infections.
CONCLUSION
Based on low to moderate quality of evidence, SGLT-2 inhibitors improve the serum level of liver enzymes, decrease liver fat, and fibrosis with additional beneficial effects on various metabolic parameters in type 2 diabetes patients with NAFLD.
PubMed: 30788048
DOI: 10.4239/wjd.v10.i2.114 -
The Cochrane Database of Systematic... Sep 2018Diabetes is the commonest cause of chronic kidney disease (CKD). Both conditions commonly co-exist. Glucometabolic changes and concurrent dialysis in diabetes and CKD... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Diabetes is the commonest cause of chronic kidney disease (CKD). Both conditions commonly co-exist. Glucometabolic changes and concurrent dialysis in diabetes and CKD make glucose-lowering challenging, increasing the risk of hypoglycaemia. Glucose-lowering agents have been mainly studied in people with near-normal kidney function. It is important to characterise existing knowledge of glucose-lowering agents in CKD to guide treatment.
OBJECTIVES
To examine the efficacy and safety of insulin and other pharmacological interventions for lowering glucose levels in people with diabetes and CKD.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 12 February 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
All randomised controlled trials (RCTs) and quasi-RCTs looking at head-to-head comparisons of active regimens of glucose-lowering therapy or active regimen compared with placebo/standard care in people with diabetes and CKD (estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m) were eligible.
DATA COLLECTION AND ANALYSIS
Four authors independently assessed study eligibility, risk of bias, and quality of data and performed data extraction. Continuous outcomes were expressed as post-treatment mean differences (MD). Adverse events were expressed as post-treatment absolute risk differences (RD). Dichotomous clinical outcomes were presented as risk ratios (RR) with 95% confidence intervals (CI).
MAIN RESULTS
Forty-four studies (128 records, 13,036 participants) were included. Nine studies compared sodium glucose co-transporter-2 (SGLT2) inhibitors to placebo; 13 studies compared dipeptidyl peptidase-4 (DPP-4) inhibitors to placebo; 2 studies compared glucagon-like peptide-1 (GLP-1) agonists to placebo; 8 studies compared glitazones to no glitazone treatment; 1 study compared glinide to no glinide treatment; and 4 studies compared different types, doses or modes of administration of insulin. In addition, 2 studies compared sitagliptin to glipizide; and 1 study compared each of sitagliptin to insulin, glitazars to pioglitazone, vildagliptin to sitagliptin, linagliptin to voglibose, and albiglutide to sitagliptin. Most studies had a high risk of bias due to funding and attrition bias, and an unclear risk of detection bias.Compared to placebo, SGLT2 inhibitors probably reduce HbA1c (7 studies, 1092 participants: MD -0.29%, -0.38 to -0.19 (-3.2 mmol/mol, -4.2 to -2.2); I = 0%), fasting blood glucose (FBG) (5 studies, 855 participants: MD -0.48 mmol/L, -0.78 to -0.19; I = 0%), systolic blood pressure (BP) (7 studies, 1198 participants: MD -4.68 mmHg, -6.69 to -2.68; I = 40%), diastolic BP (6 studies, 1142 participants: MD -1.72 mmHg, -2.77 to -0.66; I = 0%), heart failure (3 studies, 2519 participants: RR 0.59, 0.41 to 0.87; I = 0%), and hyperkalaemia (4 studies, 2788 participants: RR 0.58, 0.42 to 0.81; I = 0%); but probably increase genital infections (7 studies, 3086 participants: RR 2.50, 1.52 to 4.11; I = 0%), and creatinine (4 studies, 848 participants: MD 3.82 μmol/L, 1.45 to 6.19; I = 16%) (all effects of moderate certainty evidence). SGLT2 inhibitors may reduce weight (5 studies, 1029 participants: MD -1.41 kg, -1.8 to -1.02; I = 28%) and albuminuria (MD -8.14 mg/mmol creatinine, -14.51 to -1.77; I = 11%; low certainty evidence). SGLT2 inhibitors may have little or no effect on the risk of cardiovascular death, hypoglycaemia, acute kidney injury (AKI), and urinary tract infection (low certainty evidence). It is uncertain whether SGLT2 inhibitors have any effect on death, end-stage kidney disease (ESKD), hypovolaemia, fractures, diabetic ketoacidosis, or discontinuation due to adverse effects (very low certainty evidence).Compared to placebo, DPP-4 inhibitors may reduce HbA1c (7 studies, 867 participants: MD -0.62%, -0.85 to -0.39 (-6.8 mmol/mol, -9.3 to -4.3); I = 59%) but may have little or no effect on FBG (low certainty evidence). DPP-4 inhibitors probably have little or no effect on cardiovascular death (2 studies, 5897 participants: RR 0.93, 0.77 to 1.11; I = 0%) and weight (2 studies, 210 participants: MD 0.16 kg, -0.58 to 0.90; I = 29%; moderate certainty evidence). Compared to placebo, DPP-4 inhibitors may have little or no effect on heart failure, upper respiratory tract infections, and liver impairment (low certainty evidence). Compared to placebo, it is uncertain whether DPP-4 inhibitors have any effect on eGFR, hypoglycaemia, pancreatitis, pancreatic cancer, or discontinuation due to adverse effects (very low certainty evidence).Compared to placebo, GLP-1 agonists probably reduce HbA1c (7 studies, 867 participants: MD -0.53%, -1.01 to -0.06 (-5.8 mmol/mol, -11.0 to -0.7); I = 41%; moderate certainty evidence) and may reduce weight (low certainty evidence). GLP-1 agonists may have little or no effect on eGFR, hypoglycaemia, or discontinuation due to adverse effects (low certainty evidence). It is uncertain whether GLP-1 agonists reduce FBG, increase gastrointestinal symptoms, or affect the risk of pancreatitis (very low certainty evidence).Compared to placebo, it is uncertain whether glitazones have any effect on HbA1c, FBG, death, weight, and risk of hypoglycaemia (very low certainty evidence).Compared to glipizide, sitagliptin probably reduces hypoglycaemia (2 studies, 551 participants: RR 0.40, 0.23 to 0.69; I = 0%; moderate certainty evidence). Compared to glipizide, sitagliptin may have had little or no effect on HbA1c, FBG, weight, and eGFR (low certainty evidence). Compared to glipizide, it is uncertain if sitagliptin has any effect on death or discontinuation due to adverse effects (very low certainty).For types, dosages or modes of administration of insulin and other head-to-head comparisons only individual studies were available so no conclusions could be made.
AUTHORS' CONCLUSIONS
Evidence concerning the efficacy and safety of glucose-lowering agents in diabetes and CKD is limited. SGLT2 inhibitors and GLP-1 agonists are probably efficacious for glucose-lowering and DPP-4 inhibitors may be efficacious for glucose-lowering. Additionally, SGLT2 inhibitors probably reduce BP, heart failure, and hyperkalaemia but increase genital infections, and slightly increase creatinine. The safety profile for GLP-1 agonists is uncertain. No further conclusions could be made for the other classes of glucose-lowering agents including insulin. More high quality studies are required to help guide therapeutic choice for glucose-lowering in diabetes and CKD.
Topics: Cause of Death; Diabetes Mellitus; Diabetic Nephropathies; Dipeptidyl-Peptidase IV Inhibitors; Glipizide; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Sitagliptin Phosphate; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Thiazolidinediones
PubMed: 30246878
DOI: 10.1002/14651858.CD011798.pub2 -
World Journal of Gastroenterology Aug 2018The current epidemic of non-alcoholic fatty liver disease (NAFLD) is reshaping the field of hepatology all around the world. The widespread diffusion of metabolic risk... (Comparative Study)
Comparative Study Review
The current epidemic of non-alcoholic fatty liver disease (NAFLD) is reshaping the field of hepatology all around the world. The widespread diffusion of metabolic risk factors such as obesity, type2-diabetes mellitus, and dyslipidemia has led to a worldwide diffusion of NAFLD. In parallel to the increased availability of effective anti-viral agents, NAFLD is rapidly becoming the most common cause of chronic liver disease in Western Countries, and a similar trend is expected in Eastern Countries in the next years. This epidemic and its consequences have prompted experts from all over the word in identifying effective strategies for the diagnosis, management, and treatment of NAFLD. Different scientific societies from Europe, America, and Asia-Pacific regions have proposed guidelines based on the most recent evidence about NAFLD. These guidelines are consistent with the key elements in the management of NAFLD, but still, show significant difference about some critical points. We reviewed the current literature in English language to identify the most recent scientific guidelines about NAFLD with the aim to find and critically analyse the main differences. We distinguished guidelines from 5 different scientific societies whose reputation is worldwide recognised and who are representative of the clinical practice in different geographical regions. Differences were noted in: the definition of NAFLD, the opportunity of NAFLD screening in high-risk patients, the non-invasive test proposed for the diagnosis of NAFLD and the identification of NAFLD patients with advanced fibrosis, in the follow-up protocols and, finally, in the treatment strategy (especially in the proposed pharmacological management). These difference have been discussed in the light of the possible evolution of the scenario of NAFLD in the next years.
Topics: Alcohol Drinking; Bariatric Surgery; Biopsy; Diabetes Mellitus, Type 2; Evidence-Based Medicine; Fibrosis; Global Health; Humans; Hypoglycemic Agents; Liver; Liver Function Tests; Liver Transplantation; Magnetic Resonance Imaging; Non-alcoholic Fatty Liver Disease; Obesity; Practice Guidelines as Topic; Prevalence; Protective Agents; Risk Factors; Ultrasonography
PubMed: 30122876
DOI: 10.3748/wjg.v24.i30.3361 -
Cancer Management and Research 2018Pioglitazone has been reported to increase the risk of bladder cancer but the conclusions of published clinical studies are confusing. We conducted a systematic review... (Review)
Review
Pioglitazone has been reported to increase the risk of bladder cancer but the conclusions of published clinical studies are confusing. We conducted a systematic review and meta-analysis of all eligible randomized controlled trial (RCT) studies and observational studies, in order to identify a more precise relationship between pioglitazone and risk of bladder cancer. We searched for publications up to January 24, 2018, in PubMed, EMBASE, Scopus, Web of Science, Cochrane register, and Chinese National Knowledge Infrastructure databases, and the references of the retrieved articles and relevant reviews were also checked. Relative risk and 95% confidence interval (CI) were used to assess this correlation. A dose-related meta-analysis was performed as well. Data on RCT studies showed a null association between pioglitazone and bladder cancer. The pooled RR estimates of the 12 included studies illustrated that pioglitazone is associated with a 14% increased risk of bladder cancer (95% CI 1.03-1.26). No evidence of publication bias was detected. In the dose effect analysis, patients who used a higher dose of pioglitazone had an increased risk of bladder cancer. In conclusion, this meta-analysis indicated that pioglitazone is associated with an increased risk of bladder cancer. Further research should be conducted to confirm our findings and reveal the potential biological mechanisms.
PubMed: 29970962
DOI: 10.2147/CMAR.S164840