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Cureus Aug 2023Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent worldwide, especially in people with obesity, dyslipidemia, type 2 diabetes mellitus (T2DM),... (Review)
Review
Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent worldwide, especially in people with obesity, dyslipidemia, type 2 diabetes mellitus (T2DM), and metabolic syndrome. Weight loss and dietary modifications are established first-line treatments for NAFLD. Currently, there is no approved drug for NAFLD; however, pioglitazone and vitamin E have shown some beneficial effects. This systematic review covers the comparative efficacies of vitamin E, pioglitazone, and vitamin E plus pioglitazone. As of December 2022, the sources for prior literature review included PubMed, PubMed Central, and Medline. We included studies assessing the efficacy of pioglitazone, vitamin E, and vitamin E plus pioglitazone in improving liver histology, liver markers, and lipid profile when compared to other interventions in patients with NAFLD/non-alcoholic steatohepatitis (NASH). Review materials include randomized control trials (RCTs), traditional reviews, systematic reviews, meta-analyses, and observational studies on human participants published within the last five years in the English language. Studies on animals, pediatric populations, and with insufficient data were excluded from the review. Two authors scanned and filtered articles independently and later performed quality checks. A third reviewer resolved any conflicts. The risk of bias was assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines for systematic reviews, the Cochrane Risk of Bias Tool for RCTs, and the Scale for the Assessment of Narrative Review Articles for Traditional Reviews. A total of 21 articles were shortlisted. The results showed that pioglitazone and vitamin E are effective in reducing steatosis, inflammation, and ballooning, reducing liver markers, but there seem to be conflicting data on fibrosis resolution. Pioglitazone decreases triglycerides and increases high-density lipoproteins. One study has suggested that pioglitazone has superior efficacy to vitamin E in fibrosis reduction and vitamin E plus pioglitazone has superior efficacy than pioglitazone alone for NASH resolution. However, these conclusions require further validation through extensive analysis and additional research. In conclusion, diabetic patients with NAFLD can be given pioglitazone, and non-diabetic patients with NAFLD can be given vitamin E.
PubMed: 37719477
DOI: 10.7759/cureus.43635 -
Medical Science Monitor : International... Jul 2023BACKGROUND With the expanding understanding of conditions contributing to heightened cardiovascular risk, emerging pathologies like nonalcoholic fatty liver disease...
BACKGROUND With the expanding understanding of conditions contributing to heightened cardiovascular risk, emerging pathologies like nonalcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are being recognized as hepatic and ovarian manifestations of metabolic syndrome, respectively. This study aims to elucidate the recent advancements in our comprehension of the link between these conditions in the pediatric demographic, focusing on pathogenesis, incidence, diagnostic methods, and effective therapeutic strategies. MATERIAL AND METHODS A systematic review was conducted following the PRISMA 2020 guidelines, with a search of the PubMed database for eligible studies published in the ten years leading up to January 2023. RESULTS Out of 23 reports based on 16 original studies, we found a significantly higher prevalence of NAFLD in adolescents with PCOS compared to healthy controls. Factors such as increased de novo lipogenesis, alterations in gut microbiota, and a deficiency in growth differentiation factor-15 have been implicated in their pathogenesis. Additionally, novel biomarker S100A4, a clinical prediction score for hepatic steatosis in PCOS, and pharmacotherapy involving low-dose spironolactone, pioglitazone, and metformin have been proposed to enhance the management of these conditions. CONCLUSIONS A meticulous approach to the prevention, detection, and treatment of NAFLD in adolescents with PCOS is paramount to mitigate further complications. The study underlines the need for ongoing research to refine our understanding and management of these interconnected metabolic disorders.
Topics: Female; Adolescent; Humans; Child; Polycystic Ovary Syndrome; Non-alcoholic Fatty Liver Disease; Prevalence; Insulin Resistance
PubMed: 37455412
DOI: 10.12659/MSM.940398 -
Frontiers in Endocrinology 2023This network meta-analysis aims to compare the efficacy and safety of new anti-diabetic medications for the treatment of non-alcoholic fatty liver disease (NAFLD). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This network meta-analysis aims to compare the efficacy and safety of new anti-diabetic medications for the treatment of non-alcoholic fatty liver disease (NAFLD).
MATERIALS AND METHODS
PubMed and Scopus were searched from inception to 27 March 2022 to identify all randomized controlled trials (RCTs) in NAFLD patients. Outcomes included reductions in intrahepatic steatosis (IHS) and liver enzyme levels. The efficacy and safety of DPP-4 inhibitors, GLP-1 agonists, SGLT-2 inhibitors, and other therapies were indirectly compared using a NMA approach. Unstandardized mean difference (USMD) with 95% confidence intervals (CI) were calculated.
RESULTS
2,252 patients from 31 RCTs were included. "Add-on" GLP-1 agonists with standard of care (SoC) treatment showed significantly reduced IHS compared to SoC alone [USMD (95%CI) -3.93% (-6.54%, -1.33%)]. Surface under the cumulative ranking curve (SUCRA) identified GLP-1 receptor agonists with the highest probability to reduce IHS (SUCRA 88.5%), followed by DPP-4 inhibitors (SUCRA 69.6%) and pioglitazone (SUCRA 62.2%). "Add-on" GLP-1 receptor agonists were also the most effective treatment for reducing liver enzyme levels; AST [USMD of -5.04 (-8.46, -1.62)], ALT [USMD of -9.84 (-16.84, -2.85)] and GGT [USMD of -15.53 (-22.09, -8.97)] compared to SoC alone. However, GLP-1 agonists were most likely to be associated with an adverse event compared to other interventions.
CONCLUSION
GLP-1 agonists may represent the most promising anti-diabetic treatment to reduce hepatic steatosis and liver enzyme activity in T2DM and NAFLD patients. Nevertheless, longer-term studies are required to determine whether this delays progression of liver cirrhosis in patients with NAFLD and T2DM.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42021259336.1.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Dipeptidyl-Peptidase IV Inhibitors; Network Meta-Analysis; Glucagon-Like Peptide-1 Receptor; Randomized Controlled Trials as Topic; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1
PubMed: 37441498
DOI: 10.3389/fendo.2023.1182037 -
Journal of Clinical Medicine Jun 2023The aim of this review is to appraise the data from available randomized clinical trials (RCT) regarding the possible combinations of neuroleptic and non-antipsychotic... (Review)
Review
The aim of this review is to appraise the data from available randomized clinical trials (RCT) regarding the possible combinations of neuroleptic and non-antipsychotic treatment which could enhance antipsychotic therapy efficacy whilst simultaneously addressing somatic symptoms in individuals with schizophrenia. A systematic search of the PubMed database up to February 2022 was conducted. Inclusion criteria: randomized controlled trials using augmentation therapy in chronic schizophrenia in adults, written in English, and only studies with psychometric assessments of schizophrenia were incorporated. Exclusion criteria: non-clinical, first episode of schizophrenia, patients on medication other than antipsychotics augmented, and not adjunctive therapy. Overall, 37 studies of 1931 patients with schizophrenia who received a combination of antipsychotic medication with other drugs were selected. A statistically significant reduction of negative and positive symptoms of schizophrenia, measured with the PANSS scale, when using a combination of antipsychotic treatment along with aspirin, simvastatin, N-acetylcysteine, or pioglitazone was found. A combination of antipsychotic medication with aspirin, simvastatin, N-acetylcysteine, or pioglitazone seems to be effective in the reduction of symptoms of schizophrenia in adults, but long-term studies are required to confirm this effect.
PubMed: 37373704
DOI: 10.3390/jcm12124012 -
Reproductive Biology and Endocrinology... Mar 2023Polycystic ovarian syndrome (PCOS) is one of the most common causes of infertility in reproductive-age women. However, the efficacy and optimal therapeutic strategy for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Polycystic ovarian syndrome (PCOS) is one of the most common causes of infertility in reproductive-age women. However, the efficacy and optimal therapeutic strategy for reproductive outcomes are still under debate. We conducted a systematic review and network meta-analysis to compare the efficacy of different first-line pharmacological therapies in terms of reproductive outcomes for women with PCOS and infertility.
METHODS
A systematic retrieval of databases was conducted, and randomized clinical trials (RCTs) of pharmacological interventions for infertile PCOS women were included. The primary outcomes were clinical pregnancy and live birth, and the secondary outcomes were miscarriage, ectopic pregnancy and multiple pregnancy. A network meta-analysis based on a Bayesian model was performed to compare the effects of the pharmacological strategies.
RESULTS
A total of 27 RCTs with 12 interventions were included, and all therapies tended to increase clinical pregnancy, especially pioglitazone (PIO) (log OR 3.14, 95% CI 1.56 ~ 4.70, moderate confidence), clomiphene citrate (CC) + exenatide (EXE) (2.96, 1.07 ~ 4.82, moderate confidence) and CC + metformin (MET) + PIO (2.82, 0.99 ~ 4.60, moderate confidence). Moreover, CC + MET + PIO (2.8, -0.25 ~ 6.06, very low confidence) could increase live birth most when compared to placebo, even without a significant difference. For secondary outcomes, PIO showed a tendency to increase miscarriage (1.44, -1.69 ~ 5.28, very low confidence). MET (-11.25, -33.7 ~ 0.57, low confidence) and LZ + MET (-10.44, -59.56 ~ 42.11, very low confidence) were beneficial for decreasing ectopic pregnancy. MET (0.07, -4.26 ~ 4.34, low confidence) showed a neutral effect in multiple pregnancy. Subgroup analysis demonstrated no significant difference between these medications and placebo in obese participants.
CONCLUSIONS
Most first-line pharmacological treatments were effective in improving clinical pregnancy. CC + MET + PIO should be recommended as the optimal therapeutic strategy to improve pregnancy outcomes. However, none of the above treatments had a beneficial effect on clinical pregnancy in obese PCOS.
TRIAL REGISTRATION
CRD42020183541; 05 July 2020.
Topics: Female; Pregnancy; Humans; Network Meta-Analysis; Abortion, Spontaneous; Polycystic Ovary Syndrome; Infertility, Female; Clomiphene; Live Birth; Metformin; Obesity; Pioglitazone; Randomized Controlled Trials as Topic
PubMed: 36869381
DOI: 10.1186/s12958-023-01075-9 -
Biomedicines Jan 2023Diabetes mellitus (DM) is known to be a risk factor for dementia, especially in the elderly population, and close associations between diabetes and Alzheimer disease... (Review)
Review
Diabetes mellitus (DM) is known to be a risk factor for dementia, especially in the elderly population, and close associations between diabetes and Alzheimer disease (AD) have been determined. Peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonists are insulin-sensitising drugs. In addition to their anti-diabetic properties, their effectiveness in preventing and decreasing cognitive impairment are the most recent characteristics that have been studied. For this study, we conducted a systematic review and meta-analysis to critically analyse and evaluate the existing data on the effects of PPAR-γ agonist therapy on the cognitive status of patients. For this purpose, we first analysed both early intervention and later treatment with PPAR-γ agonists, according to the disease status. The involved studies indicated that early PPAR-γ agonist intervention is beneficial for patients and that high-dose PPAR-γ therapy may have a better clinical effect, especially in reversing the effects of cognitive impairment. Furthermore, the efficacy of pioglitazone (PIO) seems to be promising, particularly for patients with comorbid diabetes. PIO presented a better clinical curative effect and safety, compared with rosiglitazone (RSG). Thus, PPAR-γ agonists play an important role in the inflammatory response of AD or DM patients, and clinical therapeutics should focus more on relevant metabolic indices.
PubMed: 36830783
DOI: 10.3390/biomedicines11020246 -
The Cochrane Database of Systematic... Jan 2023Peroxisome 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 and October 2019.
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 (1 January 2022), the Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 12), MEDLINE (1949 to 1 January 2022), Embase (1980 to 1 January 2022), CINAHL (1982 to 1 January 2022), AMED (1985 to 1 January 2022), and 11 Chinese databases (1 January 2022). 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 certainty 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 stroke Three 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-certainty evidence). Adverse events Evidence that adverse events occurred more frequently in participants treated with PPAR-γ agonists when compared with placebo was uncertain due to wide confidence intervals and high levels of statistical heterogeneity: risk difference 10%, 95% CI -8% to 28%; low-certainty 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-certainty evidence that PPAR-γ agonists led to fewer events (data not meta-analysed). Vascular events Peroxisome 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-certainty evidence). Other outcomes One 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.
Topics: Humans; Ischemic Attack, Transient; PPAR gamma; Insulin Resistance; Stroke; Myocardial Infarction; Randomized Controlled Trials as Topic
PubMed: 36625492
DOI: 10.1002/14651858.CD010693.pub6 -
Frontiers in Cardiovascular Medicine 2022Rosiglitazone (Avandia) and pioglitazone (Actos) belong to the class of thiazolidinediones (TZDs) drugs that act by increasing insulin sensitivity and are widely used...
Thiazolidinediones play a positive role in the vascular endothelium and inhibit plaque progression in diabetic patients with coronary atherosclerosis: A systematic review and meta-analysis.
UNLABELLED
Rosiglitazone (Avandia) and pioglitazone (Actos) belong to the class of thiazolidinediones (TZDs) drugs that act by increasing insulin sensitivity and are widely used for treating diabetic patients with insulin resistance. TZDs exhibit anti-inflammatory and antioxidant properties, then may play an active role in inhibiting plaque formation and coronary atherosclerosis. But the results of evidence-based medicine suggest that TZDs may increase the risk of cardiovascular adverse events. To explore the dispute in depth, our meta-analysis aimed to evaluate the changes in vascular endothelial and plaque-related indicators following treatment with TZDs in diabetic patients with coronary atherosclerosis. According to our meta-analysis, TZDs showed an inhibiting effect on plaque progression and a protective effect on the vascular endothelium in patients with diabetes and coronary atherosclerosis. Interestingly, these effects may not depend on the regulation of inflammation and lipid metabolism. By this token, TZDs may develop a potential protective effect on myocardial infarction.
SYSTEMATIC REVIEW REGISTRATION
[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021231663].
PubMed: 36523368
DOI: 10.3389/fcvm.2022.1043406 -
Brain Sciences Nov 2022cocaine craving is a core feature of cocaine use disorder and remains a critical challenge for abstinence and relapse prevention. This review summarizes the anti-craving... (Review)
Review
BACKGROUND
cocaine craving is a core feature of cocaine use disorder and remains a critical challenge for abstinence and relapse prevention. This review summarizes the anti-craving efficacy of pharmacotherapies tested for cocaine use disorder, in the context of randomized-controlled clinical trials.
OBJECTIVES
we assessed the databases of the U.S. National Library of Medicine, Google Scholar, and PsycINFO, without date restrictions up to August 2022, to identify relevant studies.
STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS
we included double-blinded randomized-controlled trials investigating pharmacotherapies for cocaine craving and/or cocaine use disorder whose outcomes included cocaine craving.
STUDY APPRAISAL AND SYNTHESIS METHODS
Two authors screened studies' titles and abstracts for inclusion, and both read all the included studies. We systematically gathered information on the following aspects of each study: title; author(s); year of publication; sample size; mean age; sample characteristics; study set-ting; whether participants were treatment-seeking; study design; craving measures; study interventions; drop-out rates; and other relevant outcomes.
RESULTS
Overall, we appraised 130 clinical trials, including 8137 participants. We further considered the drugs from the studies that scored equal to or greater than six points in the quality assessment. There was a correlation between craving and cocaine use outcomes (self-reports, timeline follow-back or urinary benzoylecgonine) in the vast majority of studies. In the short-term treatment, acute phenylalanine-tyrosine depletion, clonidine, fenfluramine, meta-chlorophenylpiperazine (m-CPP) and mecamylamine presented promising effects. In the long term, amphetamine, biperiden, carbamazepine, lisdexamfetamine, lorcaserin, methamphetamine, mirtazapine, pioglitazone, progesterone, guanfacine, levodopa, nefazodone presented promising anti-craving effects. Unfortunately, the highly tested medications were not successful in most of the trials, as follows: propranolol in the short term; amantadine, aripiprazole, bromocriptine, citicoline, ketamine, modafinil, olanzapine, topiramate in the long term. The remaining 52 medications had no positive anti-craving outcomes.
LIMITATIONS
Our review was limited by high heterogeneity of craving assessments across the studies and by a great range of pharmacotherapies. Further, the majority of the studies considered abstinence and retention in treatment as the main outcomes, whereas craving was a secondary outcome and some of the studies evaluated patients with cocaine use disorder with comorbidities such as opioid or alcohol use disorder, schizophrenia, bipolar disorder or attention deficit hyperactivity. Lastly, most of the studies also included non-pharmacological treatments, such as counseling or psychotherapy.
CONCLUSIONS
There is a direct association between craving and cocaine use, underscoring craving as an important treatment target for promoting abstinence among persons with cocaine use disorder. Clonidine, fenfluramine and m-CPP showed to be promising medications for cocaine craving in the short-term treatment, and amphetamine, biperiden, carbamazepine, lisdexamfetamine, lorcaserin, methamphetamine, mirtazapine, pioglitazone, progesterone, guanfacine, levodopa, nefazodone in the long-term treatment.
PubMed: 36421870
DOI: 10.3390/brainsci12111546 -
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