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Drugs & Aging Jan 2015Alzheimer's disease (AD) is the most common neurodegenerative disease in the elderly, and close associations between AD and diabetes have been found. Peroxisome... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alzheimer's disease (AD) is the most common neurodegenerative disease in the elderly, and close associations between AD and diabetes have been found. Peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonists, as newly-developed oral hypoglycaemic agents, were evaluated as a possible therapy for AD.
AIM
We systematically evaluated the efficacy and safety of PPAR-γ agonists in the treatment of AD and amnestic mild cognitive impairment (aMCI), the prodromal stage of AD.
METHODS
A search of the electronic databases PubMed, EMBASE, CINAHL, Cochrane Library and China National Knowledge Infrastructure (until July 2014) was conducted, and included randomized controlled trials. Dichotomous data were expressed as risk ratios (RRs) with 95% confidence intervals (CIs), and continuous data were expressed as mean differences (MD) with 95% CIs. The results were pooled using a random-effects model.
RESULTS
Nine eligible studies were identified, with 4,327 participants. Using the Alzheimer's Disease Assessment Scale-Cognitive subscale, pioglitazone was found to be efficacious, especially for patients with comorbid diabetes (MD -3.47, 95% CI -4.40 to -2.54). Rosiglitazone was not efficacious, even for apolipoprotein E (APOE) ε4 non-carriers (MD -0.31, 95% CI -1.12 to 0.51). There was no increase in any adverse events (AEs) or serious AEs compared with placebo. Peripheral edema was the most frequent AE related to PPAR-γ agonist treatment (RR 4.14, 95% CI 2.37-7.23).
CONCLUSIONS
There is insufficient evidence to support the use of rosiglitazone in aMCI and AD patients in order to improve cognitive performance. Nonetheless, the efficacy of pioglitazone seems to be promising, particularly for patients with comorbid diabetes, however this needs to be further confirmed by well-designed trials with large sample sizes. PPAR-γ agonists such as rosiglitazone and pioglitazone are generally well-tolerated in AD and aMCI patients.
Topics: Alzheimer Disease; Cognitive Dysfunction; Humans; Hypoglycemic Agents; PPAR gamma; Pioglitazone; Randomized Controlled Trials as Topic; Rosiglitazone; Thiazolidinediones
PubMed: 25504005
DOI: 10.1007/s40266-014-0228-7 -
Clinical Endocrinology Feb 2024Characteristic features of polycystic ovary syndrome (PCOS) include insulin resistance and an increased risk for type 2 diabetes. To promote improved insulin... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Characteristic features of polycystic ovary syndrome (PCOS) include insulin resistance and an increased risk for type 2 diabetes. To promote improved insulin sensitivity, insulin sensitisers have been used in PCOS. However, direct comparisons across these agents are limited. This study compared the effects of metformin, rosiglitazone and pioglitazone in the management of PCOS to inform the 2023 International Evidence-based PCOS Guideline.
DESIGN
Systematic review and meta-analysis of the literature.
PATIENTS
Women with PCOS and treatment with insulin sensitisers.
MEASUREMENTS
Hormonal and clinical outcomes, as well as side effects.
RESULTS
Of 1660 publications identified, 13 randomised controlled trials were included. Metformin was superior in lowering weight (mean difference [MD]: -4.39, 95% confidence interval [CI]: -7.69 to -1.08 kg), body mass index (MD: -0.95, 95% CI: -1.41 to -0.49 kg/m ) and testosterone (MD: -0.10, 95% CI: -0.18 to -0.03 nmol/L) versus rosiglitazone, whereas there was no difference when comparing metformin to pioglitazone. Adding rosiglitazone or pioglitazone to metformin did not improve metabolic outcomes. However, rosiglitazone seemed superior to metformin in lowering lipid concentrations.
CONCLUSIONS
Metformin should remain the first-line insulin sensitising treatment in adults with PCOS for the prevention and management of weight and metabolic features. The addition of thiazolidinediones appears to offer little benefit.
Topics: Adult; Humans; Female; Rosiglitazone; Hypoglycemic Agents; Pioglitazone; Polycystic Ovary Syndrome; Insulin; Diabetes Mellitus, Type 2; Metformin; Thiazolidinediones; Insulin Resistance
PubMed: 37933831
DOI: 10.1111/cen.14983 -
Hormones (Athens, Greece) Dec 2023To assess the comparative efficacy of glucose-lowering drugs on liver steatosis as assessed by means of magnetic resonance imaging (MRI) in patients with T2D. (Meta-Analysis)
Meta-Analysis
Comparative efficacy of glucose-lowering drugs on liver steatosis as assessed by means of magnetic resonance imaging in patients with type 2 diabetes mellitus: systematic review and network meta-analysis.
PURPOSE
To assess the comparative efficacy of glucose-lowering drugs on liver steatosis as assessed by means of magnetic resonance imaging (MRI) in patients with T2D.
METHODS
We searched several databases and grey literature sources. Eligible trials had at least 12 weeks of intervention, included patients with T2D, and assessed the efficacy of glucose-lowering drugs as monotherapies. The primary outcome of interest was absolute reduction in liver fat content (LFC), assessed by means of MRI. Secondary efficacy outcomes were reduction in visceral and subcutaneous adipose tissue. We performed random effects frequentist network meta-analyses to estimate mean differences (MDs) with 95% confidence intervals (CIs). We ranked treatments based on P-scores.
RESULTS
We included 29 trials with 1906 patients. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors (P-score 0.84) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) (0.71) were the most efficacious in terms of liver fat content reduction. Among individual agents, empagliflozin was the most efficacious (0.86) and superior to pioglitazone (MD -5.7, 95% CI -11.2 to -0.3) (very low confidence). GLP-1 RAs had also the most favorable effects on visceral and subcutaneous adipose tissue.
CONCLUSIONS
GLP-1 RAs and SGLT-2 inhibitors seem to be the most efficacious glucose-lowering drugs for liver steatosis in patients with T2D. Assessment of their efficacy on NAFLD in patients irrespective of presence of T2D is encouraged.
Topics: Humans; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Network Meta-Analysis; Glucose; Non-alcoholic Fatty Liver Disease; Glucagon-Like Peptide 1
PubMed: 37770761
DOI: 10.1007/s42000-023-00493-z -
Diabetes, Obesity & Metabolism Apr 2021To compare different treatments for non-alcoholic steatohepatitis (NASH) and to determine an effectiveness hierarchy. (Meta-Analysis)
Meta-Analysis
AIMS
To compare different treatments for non-alcoholic steatohepatitis (NASH) and to determine an effectiveness hierarchy.
MATERIALS AND METHODS
We conducted a systematic review and Bayesian network meta-analysis including randomized controlled trials or prospective trials with at least 6 months' follow-up and histologically proven NASH in adult participants. Monte Carlo simulations were performed, each generating 10 000 data points, and results are reported as medians and 95% credibility intervals (CrIs). A meta-regression was conducted to find the effects of body mass index (BMI) decrement or reduction of homeostatic model assessment of insulin resistance (HOMA-IR) index on non-alcoholic fatty liver disease activity score (NAS) change.
RESULTS
The review identified 48 eligible trials comprising 2356 adults (55.6% men). Data were pooled using a random-effects model. The most effective treatments in terms of NAS reduction per semester were pioglitazone and Roux-en-Y gastric bypass (RYGB; -1.50 [95% CrI -2.08, -1.00] for pioglitazione and -1.00 [95% CrI -1.70, -0.32] for RYGB). Pioglitazone was also the best therapy for steatosis and lobular inflammation reduction. RYGB was the best treatment for hepatocellular ballooning reduction, whereas antioxidants appeared to be best for fibrosis improvement. For each 1% decrement in BMI, NAS was reduced by 1.3% (β = 1.28%, P = 0.01). Conversely, a 1% reduction of HOMA-IR index reduced NAS by 0.3% (β = 0.31%, P < 0.001). Treatments that were regarded as promising, such as elafibranor, simtuzumab, selonsertib, cenicriviroc, obeticholic acid and liraglutide, did not reduce either NAS or liver fibrosis significantly.
CONCLUSIONS
Pioglitazione and RYGB are the most effective therapies for NASH. Antioxidants may be effective in reducing liver fibrosis. Weight loss and improvement of hepatic insulin resistance are promising approaches in the treatment of NASH.
Topics: Adult; Bariatric Surgery; Bayes Theorem; Female; Humans; Liver; Male; Network Meta-Analysis; Non-alcoholic Fatty Liver Disease; Pioglitazone; Prospective Studies
PubMed: 33368954
DOI: 10.1111/dom.14304 -
Acta Gastro-enterologica Belgica 2022Metabolic dysfunction-associated fatty liver disease (MAFLD) is the evidence of steatosis in the setting of a metabolic risk condition such as type 2 diabetes mellitus... (Review)
Review
Non-invasive screening, staging and management of metabolic dysfunction-associated fatty liver disease (MAFLD) in type 2 diabetes mellitus patients: what do we know so far ?
Metabolic dysfunction-associated fatty liver disease (MAFLD) is the evidence of steatosis in the setting of a metabolic risk condition such as type 2 diabetes mellitus (T2DM). Indeed, T2DM and liver steatosis share common pathophysiological mechanisms, and one can lead to the other. MAFLD can progress from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis as well as hepatocellular carcinoma (HCC). Because of the lack / disparity of guidelines for MAFLD screening, which is asymptomatic in its early stages, it is not rare that diabetic patients are belatedly diagnosed with NASH cirrhosis or HCC. We therefore recommend systematic non-invasive tests (NITs) that calculate an estimate of the risk based on readily available anthropometric and biological parameters. These include the fatty liver index (FLI) for steatosis detection and at least one of the following for fibrosis: non-alcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 index (FIB-4) or Hepamet fibrosis score (HFS). Indeed, NFS and FIB-4 are the best predictors of liver-related events, while FIB-4 and HFS correlate with overall mortality. Systematic literature review found only few retrospective or cross-sectional studies using NITs for systematic steatosis and fibrosis screening in T2DM patients, with a crucial need for prospective studies. This screening strategy will allow targeted patients to be referred for further liver investigation (e.g. ultrasound, elastometry) and care. Current treatment modalities of MAFLD in T2DM patients range from lifestyle and dietary interventions to specific glucose-lowering drugs that recently showed some benefits regarding MAFLD, such as pioglitazone, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors. Other treatments are currently under investigation.
Topics: Carcinoma, Hepatocellular; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Glucose; Humans; Liver Cirrhosis; Liver Neoplasms; Non-alcoholic Fatty Liver Disease; Prospective Studies; Retrospective Studies; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 35709779
DOI: 10.51821/85.2.9775 -
Clinical Endocrinology Apr 2022Polycystic ovary syndrome (PCOS) is a heterogeneous condition affecting women of reproductive age. It is associated with dyslipidaemia and elevated plasma C-reactive... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Polycystic ovary syndrome (PCOS) is a heterogeneous condition affecting women of reproductive age. It is associated with dyslipidaemia and elevated plasma C-reactive protein (CRP), which increase the risks of cardiovascular disease (CVD).
OBJECTIVE
To review the existing evidence on the effects of different pharmacological interventions on lipid profiles and CRP of women with PCOS.
DATA SOURCES
We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library, and Web of Science in April 2020 and updated the results in March 2021.
STUDY SELECTION
The study included randomized controlled trials (RCTs) and follows the 2020 Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA).
DATA EXTRACTION
Two independent researchers extracted data and assessed for risk of bias using the Cochrane risk of bias tool. Covidence systematic review software were used for blinded screening and study selection.
DATA SYNTHESIS
In 29 RCTs, there were significant reductions in triglycerides with atorvastatin versus placebo [mean difference (MD): -0.21 mmol/L; 95% confidence interval (CI): -0.39, -0.03, I = 0%, moderate grade evidence]. Significant reductions were seen for low-density lipoprotein cholesterol (LDL-C) with metformin versus placebo [standardized mean difference (SMD): -0.41; 95% CI: -0.85, 0.02, I = 59%, low grade evidence]. Significant reductions were also seen for total cholesterol with saxagliptin versus metformin (MD: -0.15 mmol/L; 95% CI: -0.23, -0.08, I = 0%, very low grade evidence). Significant reductions in C-reactive protein (CRP) were seen for atorvastatin versus placebo (MD: -1.51 mmol/L; 95% CI: -3.26 to 0.24, I = 75%, very low-grade evidence).
CONCLUSION
There were significant reductions in the lipid parameters when metformin, atorvastatin, saxagliptin, rosiglitazone and pioglitazone were compared with placebo or other agents. There was also a significant reduction of CRP with atorvastatin.
Topics: Atorvastatin; C-Reactive Protein; Cholesterol, LDL; Female; Humans; Metformin; Polycystic Ovary Syndrome
PubMed: 34779013
DOI: 10.1111/cen.14636 -
A Systematic Review and Bayesian Network Meta-Analysis of Medical Therapies for Lichen Planopilaris.Dermatology (Basel, Switzerland) 2024Lichen planopilaris (LPP) is a primary chronic lymphocytic cutaneous disorder that selectively destroys the hair follicles, resulting in scarring alopecia.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lichen planopilaris (LPP) is a primary chronic lymphocytic cutaneous disorder that selectively destroys the hair follicles, resulting in scarring alopecia. Unfortunately, current available treatments are not fully effective to stop hair loss, and the level of evidence for medical interventions is weak.
OBJECTIVES
The present article aimed to determine the efficacy of the different medical interventions in LPP through a network meta-analysis (NMA).
METHODS
A systematic review and meta-analysis were performed including randomized trials that report the outcomes of lichen planopilaris activity index (LPPAI). These articles were pooled and a NMA was conducted.
RESULTS
A total of seven studies were identified and included in meta-analysis, comprising 251 LPP patients. The NMA showed the mean difference in LLPAI was significantly superior with the combination of clobetasol plus N-acetylcysteine (mean difference: -2.0, 95% CI = -3.43 to -0.51) and the combination of clobetasol plus pentoxifylline (mean difference: -1.62, 95% CI = -3.0 to -0.25) compared to the treatment of reference (clobetasol). The NMA showed cyclosporine (mean difference: 2.05 95% CI = 0.68-3.49), methotrexate (mean difference: 1.95 95% CI = 1.23-3.17), the combination of methotrexate plus prednisolone (mean difference: 1.56 95% CI = 0.25-2.96) were significantly worse than hydroxychloroquine according to the differences in LLPAI.
CONCLUSION
This work is the first NMA in LPP and hence, it can be helpful in serving as an initial step toward better evidence-based decisions in the treatment of this challenging condition. We propose a triple-combined approach consisting of topical clobetasol, hydroxychloroquine, and N-acetylcysteine as resulted in the most effective approach. Considering the poor outcomes observed with pioglitazone, mycophenolate mofetil, and cyclosporine, it is advisable to contemplate the use of these medications in patients who have not responded adequately to more efficacious alternatives.
Topics: Humans; Clobetasol; Methotrexate; Network Meta-Analysis; Acetylcysteine; Bayes Theorem; Hydroxychloroquine; Lichen Planus; Cyclosporine; Alopecia; Chronic Disease
PubMed: 37852211
DOI: 10.1159/000534364 -
Medicine Nov 2022Nonalcoholic steatohepatitis is regarded as a risk factor of many liver diseases. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Nonalcoholic steatohepatitis is regarded as a risk factor of many liver diseases.
METHODS
Relevant studies were searched from The National Library of Medicine, Cochrane Library, Elsevier, China National Knowledge Infrastructure, Web of Science and WANFANG databases. A total of 15 eligible studies were analyzed in the Reviewer Manager 5.3 software, including 7 English articles and 8 Chinese articles.
RESULTS
Fifteen studies are selected for this meta-analysis, which includes totally 623 patients in the treatment group and 594 patients in the control group. As a result, 8 studies show that the total effective rate of the treatment group is higher than that of the control group [Z = 3.64, 95% confidence intervals (CI): 1.78 (1.31-2.43), P = .0003]; eleven studies show that fasting plasma glucose levels of the experimental group are lower than that of the control group [Z = 4.38, 95% CI: -0.95 (-1.38 to -0.53), P < .0001]; ten studies show that glutamic-pyruvic transaminase levels of the experimental group are lower than that of the control group [Z = 3.69, 95% CI: -11.76 (-18.01 to -5.51), P = .0002]; 6 studies show that glutamic oxalacetic transaminase levels of the experimental group are lower than that of the control group [Z = 7.40, 95% CI: -3.01 (-3.81 to -2.22), P < .00001]; 6 studies show that gamma-glutamyl transpeptidase levels of the experimental group are lower than that of the control group [Z = 2.43, 95% CI: -23.77 (-42.98 to -4.57), P = .02]; 9 studies show that triglyceride levels of the experimental group are lower than that of the control group [Z = 3.06, 95% CI: -0.62 (-1.01 to -0.22), P = .002]; 6 studies show that the homeostasis model assessment of insulin resistance of the experimental group is lower than that of the control group [Z = 3.22, 95% CI: -2.33 (-3.75 to -0.91), P = .001]; 6 studies show that the glycated hemoglobin A1c of the experimental group is lower than that of the control group [Z = 4.50, 95% CI: -1.90 (-2.72 to -1.07), P < .00001]; five studies show that the fasting insulin of the experimental group is lower than that of the control group [Z = 3.42, 95% CI: -2.25 (-3.53 to -0.96), P = .0006].
CONCLUSION
Pioglitazone intake is effective in nonalcoholic steatohepatitis management.
Topics: Humans; United States; Non-alcoholic Fatty Liver Disease; Pioglitazone; Insulin Resistance; Insulin; Glycated Hemoglobin
PubMed: 36401449
DOI: 10.1097/MD.0000000000031508 -
The Journal of Dermatological Treatment Nov 2020A growing number of studies have shown that thiazolidinediones (TZD) can be antipsoriatic. Pioglitazone is a representative of the class of antidiabetic drugs known as... (Meta-Analysis)
Meta-Analysis
A growing number of studies have shown that thiazolidinediones (TZD) can be antipsoriatic. Pioglitazone is a representative of the class of antidiabetic drugs known as TZD. TZD can activate nuclear peroxisome proliferator-activated receptors (PPAR)-c. PPARs are expressed on epidermal keratinocytes and exert their effects by promoting the terminal differentiation of keratinocytes, inhibiting epidermal growth, and reducing inflammatory responses. These observations suggest that TZD have potential benefits in the treatment of cutaneous and metabolic pathologies associated with psoriasis. A systematic review and meta-analysis was carried out to evaluate the efficacy of combined pioglitazone treatment. We point out three controversial side effects from administration of pioglitazone in psoriasis: elevated liver enzymes, weight gain, and nausea. Randomized, single blind, or double blind, published studies of pioglitazone compared with placebo given to patients with plaque psoriasis for 10 weeks or 12 weeks were considered for inclusion in this review. The primary outcomes were 75% or greater improvement in the Psoriasis Area and Severity Index score from baseline (PASI 75) with pioglitazone. The systematic literature search was conducted in the PubMed, Embase, Google Scholar, and Cochrane databases from inception up to December 20 2018. Data analysis was done using Revman 5.3 Haymarket, London, United Kingdom. We included six studies (three publications of pioglitazone only; three publications of pioglitazone combination therapy) comprising a total of 294 patients ( = 149 with pioglitazone only and = 145 with pioglitazone combination therapy) in the analysis. There was a significant PASI 75 response, in the pioglitazone only subgroup as compared to placebo (OR = 8.74, 95% CI 3.76-20.31, < .00001), and the pioglitazone combination subgroup as compared to placebo (OR = 4.64, 95% CI 2.03-10.60, < .00001), others, the total of pioglitazone as compared to placebo (OR = 6.37, 95% CI 3.55-11.43, < .00001), and tests of subgroup differences show: = .29, I2 = 9.5%. The incidence rate of elevated liver enzymes (OR = 3.70, 95% CI 0.56-24.31, = .99), weight gain (OR = 1.44, 95% CI 0.60-3.47, = .41), and nausea (OR = 0.76, 95% CI 0.23-2.49, = .65) were not significantly different compared with the control group. Pioglitazone has efficacy for the treatment of plaque psoriasis. There is no significant difference between patients treated with pioglitazone only or in combination with other therapies. The incidence rate of side effects associated with pioglitazone treatment such as elevated liver enzymes, weight gain, and nausea were not significantly different compared with the control group.
Topics: Combined Modality Therapy; Dermatologic Agents; Drug Therapy, Combination; Humans; Phototherapy; Pioglitazone; Psoriasis; Randomized Controlled Trials as Topic; United Kingdom
PubMed: 31116619
DOI: 10.1080/09546634.2019.1610552 -
Nutrition, Metabolism, and... Mar 2022In 2019, the Italian Society of Diabetology and the Italian Association of Clinical Diabetologists nominated an expert panel to develop guidelines for drug treatment of... (Meta-Analysis)
Meta-Analysis
AIM
In 2019, the Italian Society of Diabetology and the Italian Association of Clinical Diabetologists nominated an expert panel to develop guidelines for drug treatment of type 2 diabetes. After identifying the effects of glucose-lowering agents on major adverse cardiovascular events (MACEs), all-cause mortality, and hospitalization for heart failure (HHF) as critical outcomes, the experts decided to perform a systematic review and meta-analysis on the effect of pioglitazone with this respect.
DATA SYNTHESIS
A MEDLINE database search was performed to identify RCTs, up to June 1st, 2021, with duration≥52 weeks, in which pioglitazone was compared with either placebo or active comparators. The principal endpoints were MACE and HHF (restricted for RCT reporting MACEs within their outcomes), all-cause mortality (irrespective of the inclusion of MACEs among the pre-specified outcomes). Mantel-Haenszel odds ratio (MH-OR) with 95% Confidence Interval (95% CI) was calculated for all the endpoints considered. Eight RCTs were included in the analysis for MACEs and HF (5048 and 5117 patients in the pioglitazone and control group, respectively), and 24 in that for all-cause mortality (10,682 and 9674 patients). Pioglitazone neither significantly increased nor reduced the risk of MACE, all-cause mortality, and HHF in comparison with placebo/active comparators (MH-OR: 0.90, 95% CI 0.78-1.03, 0.91, 95% CI 0.77, 1.09, and 1.16, 95% CI 0.73, 1.83, respectively). Pioglitazone was associated with a significant reduction of MACE in patients with prior cardiovascular events (MH-OR 0.84, 95% CI 0.72-0.99).
CONCLUSIONS
This meta-analysis showed no significant effects of pioglitazone on incident MACE, all-cause mortality, and HHF.
Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Pioglitazone; Randomized Controlled Trials as Topic
PubMed: 35144855
DOI: 10.1016/j.numecd.2021.12.006