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Frontiers in Endocrinology 2024Overweight and obesity are increasing global public health problems. Mazdutide is a new dual agonist drug that can potentially reduce weight and blood glucose levels... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Overweight and obesity are increasing global public health problems. Mazdutide is a new dual agonist drug that can potentially reduce weight and blood glucose levels simultaneously. However, the synthesis of evidence on the efficacy and safety of this drug is scarce. Therefore, this study aimed to synthesize evidence on the efficacy and safety of Mazdutide compared to placebo on weight reduction among adults with and without diabetes.
METHODS
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). Data were retrieved from six electronic databases: PubMed, Web of Science, Scopus, Cochrane Library, ClinicalTrial.gov, and Google Scholar, and manually searched from the included references. The data were synthesized using a random effect model. This analysis was performed in the R programming language using the Meta package.
RESULTS
A total of seven RCTs involving 680 participants were included in this study. Mazdutide was more effective in reducing body weight (mean difference [MD]= -6.22%, 95% confidence interval [CI]: -8.02% to -4.41%, I = 90.0%), systolic blood pressure (MD = -7.57 mmHg, 95% CI: -11.17 to -3.98 mmHg, I = 46%), diastolic blood pressure (MD = -2.98 mmHg, 95% CI: -5.74 to -0.22 mmHg, I = 56%), total cholesterol (MD = -16.82%, 95% CI: -24.52 to -9.13%, I = 61%), triglycerides (MD = -43.29%, 95% CI: -61.57 to -25.01%, I = 68%), low-density lipoprotein (MD= -17.07%, 95% CI: -25.54 to -8.60%, I = 53%), and high-density lipoprotein (MD = -7.54%, 95% CI: -11.26 to -3.83%, I = 0%) than placebo. Mazdutide was associated with reduced hemoglobin A1c (HbA1c) and fasting plasma glucose in participants with type 2 diabetes. In the subgroup and meta-regression analyses, weight reduction was more significant in non-diabetics compared to diabetics, and in those who received a longer treatment duration (24 weeks) than in those on shorter durations (12-20 weeks). Participants who received Mazdutide had a higher risk of transient mild or moderate gastrointestinal side effects.
CONCLUSION
Mazdutite appears to be effective in weight reduction among patients with and without diabetes, and it has an advantage over other associated comorbidities. However, it was associated with mild or moderate gastrointestinal side effects.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=403859, identifier CRD42023403859.
Topics: Humans; Diabetes Mellitus, Type 2; Fasting; Peptides; Randomized Controlled Trials as Topic; Weight Loss
PubMed: 38440786
DOI: 10.3389/fendo.2024.1309118 -
European Journal of Clinical... Mar 2024Brown adipose tissue (BAT) has emerged as a potential therapeutic target for metabolic disorders due to its thermogenic and anti-obesity properties. β3-adrenergic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Brown adipose tissue (BAT) has emerged as a potential therapeutic target for metabolic disorders due to its thermogenic and anti-obesity properties. β3-adrenergic receptor (β3-AR) agonists have also gained attention as potential agents for BAT activation and metabolic regulation. Mirabegron, a selective β3-AR-agonist used clinically for overactive bladder syndrome, has been explored for its utility in metabolic disorders. However, the controversy surrounding the ability of mirabegron to activate BAT to accelerate metabolism requires further investigation. The aim of this systematic review is to characterize comprehensively the impact of mirabegron on human BAT and its metabolism.
METHODS
We searched PubMed Central, Web of Science, Embase, and Cochrane Library databases for relevant papers published from the date of database inception to March 2023 for systematic reviews and meta-analyses. We extracted data on primary outcome indicators such as BAT volume, BAT activity, body temperature, and resting energy expenditure (REE), as well as secondary outcome indicators such as heart rate (HR), diastolic blood pressure (DBP), systolic blood pressure (SBP), non-esterified fatty acids (NEFA), blood glucose, and blood insulin from relevant studies. For studies that did not provide suitable data for meta-analysis, we used narrative data synthesis. For studies that provided suitable data for meta-analysis, we conducted meta-analysis using RevMan 5.4 software.
RESULTS
We reviewed 10 papers and included 6 in our meta-analysis. Our findings revealed no significant changes in BAT volume (p = 0.72) or blood glucose (p = 0.52) with mirabegron when compared to the placebo or pre-dose population. However, patients showed significant increases in BAT activity (p < 0.01), blood NEFA (p < 0.01), body temperature (p < 0.01), REE (p < 0.01), HR (p < 0.01), DBP (p < 0.01), SBP (p = 0.25), and blood insulin (p < 0.01).
CONCLUSION
Through our meta-analysis of 6 papers, we found that mirabegron has the potential to increase human BAT activity, REE, NEFA content, body temperature, HR, blood pressure, and blood insulin content. These effects may lead to reductions in blood glucose levels in obese/overweight and diabetic patients. Additionally, the activation of BAT by mirabegron could represent a novel approach for treating obesity, diabetes, and cardiovascular disease.
TRIAL REGISTRATION NUMBER AND DATE
CRD42023413446, 04/11/2023.
Topics: Humans; Acetanilides; Adipose Tissue, Brown; Blood Glucose; Diabetes Mellitus; Fatty Acids, Nonesterified; Insulins; Obesity; Thiazoles
PubMed: 38159219
DOI: 10.1007/s00228-023-03614-0 -
Archives of Medical Research Dec 2023Predictors of first-generation somatostatin receptor ligands (fgSRLs) response in acromegaly have been studied for over 30 years, but they are still not recommended in...
BACKGROUND AND AIMS
Predictors of first-generation somatostatin receptor ligands (fgSRLs) response in acromegaly have been studied for over 30 years, but they are still not recommended in clinical guidelines. Is there not enough evidence to support their use? This systematic review aims to describe the current knowledge of the main predictors of fgSRLs response and discuss their current usefulness, as well as future research directions.
METHODS
A systematic search was performed in the Scopus and PubMed databases for functional, imaging, and molecular predictive factors.
RESULTS
A total of 282 articles were detected, of which 64 were included. Most of them are retrospective studies performed between 1990 and 2023 focused on the predictive response to fgSRLs in acromegaly. The usefulness of the predictive factors is confirmed, with good response identified by the most replicated factors, specifically low GH nadir in the acute octreotide test, T2 MRI hypointensity, high Somatostatin receptor 2 (SSTR2) and E-cadherin expression, and a densely granulated pattern. Even if these biomarkers are interrelated, the association is quite heterogeneous. With classical statistical methods, it is complex to define reliable and generalizable cut-off values worth recommending in clinical guidelines. Machine-learning models involving omics are a promising approach to achieve the highest accuracy values to date.
CONCLUSIONS
This survey confirms a sufficiently robust level of evidence to apply knowledge of predictive factors for greater efficiency in the treatment decision process. The irruption of artificial intelligence in this field is providing definitive answers to such long-standing questions that may change clinical guidelines and make personalized medicine a reality.
Topics: Humans; Acromegaly; Somatostatin; Receptors, Somatostatin; Retrospective Studies; Artificial Intelligence; Treatment Outcome
PubMed: 38042683
DOI: 10.1016/j.arcmed.2023.102924 -
International Journal of Molecular... Feb 2024Cannabidiol (CBD), a non-psychoactive phytocannabinoid abundant in , has gained considerable attention for its anti-inflammatory, antioxidant, analgesic, and... (Review)
Review
Cannabidiol (CBD), a non-psychoactive phytocannabinoid abundant in , has gained considerable attention for its anti-inflammatory, antioxidant, analgesic, and neuroprotective properties. It exhibits the potential to prevent or slow the progression of various diseases, ranging from malignant tumors and viral infections to neurodegenerative disorders and ischemic diseases. Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease, and viral hepatitis stand as prominent causes of morbidity and mortality in chronic liver diseases globally. The literature has substantiated CBD's potential therapeutic effects across diverse liver diseases in in vivo and in vitro models. However, the precise mechanism of action remains elusive, and an absence of evidence hinders its translation into clinical practice. This comprehensive review emphasizes the wealth of data linking CBD to liver diseases. Importantly, we delve into a detailed discussion of the receptors through which CBD might exert its effects, including cannabinoid receptors, CB1 and CB2, peroxisome proliferator-activated receptors (PPARs), G protein-coupled receptor 55 (GPR55), transient receptor potential channels (TRPs), and their intricate connections with liver diseases. In conclusion, we address new questions that warrant further investigation in this evolving field.
Topics: Humans; Cannabidiol; Receptors, Cannabinoid; Cannabis; Digestive System Diseases; Liver Diseases, Alcoholic; Receptor, Cannabinoid, CB1
PubMed: 38397045
DOI: 10.3390/ijms25042370 -
Journal of Trace Elements in Medicine... Sep 2023Inflammation is an initiating cause of infectious and non-infectious diseases. Studies have shown that selenium (Se) has anti-inflammatory effects. However, its' effects... (Meta-Analysis)
Meta-Analysis Review
Inflammation is an initiating cause of infectious and non-infectious diseases. Studies have shown that selenium (Se) has anti-inflammatory effects. However, its' effects on serum c-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) plasma concentrations are equivocal. Therefore, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs), evaluating the effects of per oral (PO) and intravenous (IV) Se supplementation on CRP, TNF-α, and IL-6. A systematic search was conducted using four databases, including PubMed, Google Scholar, Cochrane Library, and Scopus to find randomized clinical trials, published up to April 2023. From 19476 papers, after screening and removing duplicate articles, 24 studies were analyzed in the present meta-analysis. In the pooled analysis, PO Se administration showed no significant effect on CRP (WMD: 0.12; 95 % CI -0.11, 0.38; P-value= 0.30). However, IV Se supplementation had a significant negative association with CRP concentration (-2.24; 95 % CI: -4.24, -0.24; p-value: 0.02). Se administration had no significant association with TNF-α plasma concentration (9.64, 95 % CI: -0.59, 19.88, p-value= 0.06; and heterogeneity: 98 %). However, a significant positive association was present between Se and plasma TNF-α concentrations (0.15, 95 % CI: 0.14, 0.17, P-value<0.0001). Moreover, Se supplementation had a significant negative correlation with IL-6 plasma concentration in PO (-0.54; 95 % CI: -1.61, 0.52; P-value = 0.31) and IV administrations (-4.77; 95 % CI: -7.61, -1.93; P-value<0.0001), respectively. This study demonstrated that IV Se administration reduced CRP and IL-6 plasma concentrations. Conversely, IV Se supplementation increased TNF-α plasma concentration. It is evident that further, well-controlled clinical trials are required.
Topics: Humans; C-Reactive Protein; Interleukin-6; Tumor Necrosis Factor-alpha; Selenium; Dietary Supplements; Randomized Controlled Trials as Topic; Inflammation; Biomarkers
PubMed: 37257335
DOI: 10.1016/j.jtemb.2023.127199 -
Frontiers in Endocrinology 2024Existing evidence on the possible effects of probiotics on obese or overweight adolescents has not been fully established. Therefore, the aim of this study was to... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Existing evidence on the possible effects of probiotics on obese or overweight adolescents has not been fully established. Therefore, the aim of this study was to explore the effects of probiotic supplementation on anthropometric indices, inflammatory markers and metabolic indices in obese or overweight adolescents.
METHODS
The literature up to March 2023 related to probiotic intervention in obese or overweight adolescents was searched and screened from multiple databases, including the CNKI(China national knowledge infrastructure), CBM(Chinese biomedical literature database), PubMed, EmBase, and Cochrane library databases. All randomized controlled trials using probiotic supplements in obese or overweight adolescents were included in this systematic review and meta-analysis.
RESULTS
A total of 8 studies that met the inclusion criteria were included in this study. There were 201 cases in the experimental group (probiotic treatment) and 190 cases in the control group. Compared to the control group, probiotic intervention in adolescents resulted in a decrease in body mass index, fasting blood glucose and C-reactive protein with WMD(Weighted mean difference) and 95% CI of -2.53 (-4.8 to -0.26) kg/m, -0.80 (-1.13 to -0.47) mol/L and -0.24 (-0.43 to -0.05) mg/L, respectively. No significant changes were found in weight, waist circumference, waist-to-hip ratio, insulin, Homeostatic Model Assessment of insulin resistance, interleukin 6, tumor necrosis factor alpha and so on; however, an unfavorable elevated effect in total cholesterol, triglycerides, and low-density lipoproteins was detected with WMD and 95% CI of 0.06 (0.02 to 0.09) mmol/L, 0.18 (0.14 to 0.21) mmol/L, and 0.19 (0.18 to 0.20) mmol/L, respectively.
CONCLUSION
According to our results, probiotic supplementation was beneficial in managing metabolic indicators such as fasting blood glucose, body mass index and inflammation-related C-reactive protein in overweight or obese adolescents. Further large scale studies are warranted to confirm present findings and to identify the effects and mechanisms to provide more precise evidence for clinical intervention.
SYSTEMATIC REVIEW REGISTRATION
doi: 10.37766/inplasy2024.1.0081, identifier INPLASY202410081.
Topics: Adolescent; Humans; Overweight; Blood Glucose; C-Reactive Protein; Obesity; Probiotics; Randomized Controlled Trials as Topic
PubMed: 38352715
DOI: 10.3389/fendo.2024.1335810 -
JBMR Plus Nov 2023Diabetes poses a significant risk to bone health, with Type 1 diabetes (T1D) having a more detrimental impact than Type 2 diabetes (T2D). The group of hormones known as... (Review)
Review
Diabetes poses a significant risk to bone health, with Type 1 diabetes (T1D) having a more detrimental impact than Type 2 diabetes (T2D). The group of hormones known as incretins, which includes gastric inhibitory peptide (GIP) and glucagon-like peptide 1 (GLP-1), play a role in regulating bowel function and insulin secretion during feeding. GLP-1 receptor agonists (GLP-1 RAs) are emerging as the primary treatment choice in T2D, particularly when atherosclerotic cardiovascular disease is present. Dipeptidyl peptidase 4 inhibitors (DPP-4is), although less potent than GLP-1 RAs, can also be used. Additionally, GLP-1 RAs, either alone or in combination with GIP, may be employed to address overweight and obesity. Since feeding influences bone turnover, a relationship has been established between incretins and bone health. To explore this relationship, we conducted a systematic literature review following the PRISMA guidelines. While some studies on cells and animals have suggested positive effects of incretins on bone cells, turnover, and bone density, human studies have yielded either no or limited and conflicting results regarding their impact on bone mineral density (BMD) and fracture risk. The effect on fracture risk may vary depending on the choice of comparison drug and the duration of follow-up, which was often limited in several studies. Nevertheless, GLP-1 RAs may hold promise for people with T2D who have multiple fracture risk factors and poor metabolic control. Furthermore, a potential new area of interest is the use of GLP-1 RAs in fracture prevention among overweight and obese people. Based on this systematic review, existing evidence remains insufficient to support a positive or a superior effect on bone health to reduce fracture risk in people with T2D. © 2023 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
PubMed: 38025038
DOI: 10.1002/jbm4.10817 -
Clinical Therapeutics Mar 2024The aging of the population increases the incidence of postmenopausal osteoporosis, which threatens the health of elderly women. Abaloparatide is a synthetic peptide... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The aging of the population increases the incidence of postmenopausal osteoporosis, which threatens the health of elderly women. Abaloparatide is a synthetic peptide analogue of the human parathyroid hormone-related protein that has recently been approved for the treatment of postmenopausal osteoporosis. Its efficacy and safety have not been systematically evaluated. Therefore, studies on the efficacy and safety of abaloparatide could be of assistance in the clinical medication of postmenopausal osteoporosis. The aim of this study was to evaluate the clinical efficacy and safety of abaloparatide in postmenopausal osteoporosis.
METHODS
PubMed, Cochrane Library, EMBASE, and Web of Science databases were electronically searched from inception to July 6, 2023, for relevant randomized controlled trials. Two review authors independently conducted the study screening, quality assessment (based on the Risk of Bias Assessment Tool recommended in the Cochrane handbook), and data extraction. Outcome measures included bone mineral density (BMD), bone turnover and metabolic markers, incidence of fractures, and adverse events. Data analyses were processed by using Stata SE15.
FINDINGS
Ultimately, 8 randomized controlled trials, involving a total of 3705 postmenopausal women, were included. Meta-analysis showed that abaloparatide administration significantly increased the BMD of the lumbar vertebrae (standardized mean difference [SMD], 1.28 [95% CI, 0.81-1.76); I = 78.5%]), femoral neck (SMD, 0.70 [95% CI, 0.17-1.23; I = 75.7%]), and hip bone (SMD, 0.86 [95% CI, 0.53-1.20; I = 60.4%]) in postmenopausal women compared with the control group. Type I procollagen N-terminal propeptide, a bone formation marker, was also elevated after abaloparatide administration. The incidence of vertebral fracture was lower in the abaloparatide group than in the control group (risk ratio, 0.13; 95% CI, 0.06-0.26; I = 0%). There was no significant difference in the incidence of adverse events between the abaloparatide and the placebo groups (risk ratio, 1.03; 95% CI, 0.99-1.06; I = 0%).
IMPLICATIONS
Abaloparatide has a protective effect on women with postmenopausal osteoporosis. It could reduce their risk for vertebral fracture; increase their BMD of the lumbar spine, femoral neck, and hip; and alleviate symptoms and complications of postmenopausal osteoporosis with considerable safety. Limitations of this study include not searching the gray literature and not performing a subgroup analysis. PROSPERO Registration No.: CRD42022370944.
Topics: Female; Humans; Aged; Osteoporosis, Postmenopausal; Parathyroid Hormone-Related Protein; Spinal Fractures; Bone Density Conservation Agents; Bone Density
PubMed: 38307725
DOI: 10.1016/j.clinthera.2023.12.010 -
World Journal of Hepatology Aug 2023Non-alcoholic fatty liver disease (NAFLD) has become a prevalent cause of chronic liver disease and ranks third among the causes of transplantation. In the United States...
BACKGROUND
Non-alcoholic fatty liver disease (NAFLD) has become a prevalent cause of chronic liver disease and ranks third among the causes of transplantation. In the United States alone, annual medical costs are approximately 100 billion dollars. Unfortunately, there is no Federal Drug Administration (FDA)-approved medication for its treatment. However, various clinical trials are investigating several therapeutic classes that could potentially treat NAFLD. It is valuable to have a compilation of the data available on their efficacy.
AIM
To assess the efficacy of cyclophilin inhibitors, fibroblast growth factor 21 analogs (FGF21), and dual and pan peroxisome proliferator-activated receptor (PPAR) agonists for treating NAFLD.
METHODS
A comprehensive literature search using keywords including cyclophilin inhibitor, FGF agonist, pan-PPAR agonists, dual-PPAR agonist, NAFLD, non-alcoholic steatohepatitis, and fatty liver was conducted on October 29, 2022, in PubMed, EMBASE, Cochrane Library, Scopus and Web of Science. Animal and human research, case reports, and published articles in English from all countries with patients aged 18 and above were included. Only articles with a National Institutes of Health (NIH) Quality Assessment score of five or higher out of eight points were included. Articles that were narrative or systematic reviews, abstracts, not in English, focused on patients under 18 years old, did not measure outcomes of interest, were inaccessible, or had a low NIH Quality Assessment score were excluded. Each article was screened by two independent researchers evaluating relevance and quality. Resources were scored based on the NIH Quality Assessment Score; then, pertinent data was extracted in a spreadsheet and descriptively analyzed.
RESULTS
Of the 681 records screened, 29 met the necessary criteria and were included in this review. These records included 12 human studies and 17 animal studies. Specifically, there were four studies on cyclophilin inhibitors, four on FGF agonists/analogs, eleven on pan-PPAR agonists, and ten on dual-PPAR agonists. Different investigational products were assessed: The most common cyclophilin inhibitor was NV556; FGF agonists and analogs was Efruxifermin; pan-PPAR agonists was Lanifibranor; and dual-PPAR agonists was Saroglitazar. All classes were found to be statistically efficacious for the treatment of NAFLD, with animal studies demonstrating improvement in steatosis and/or fibrosis on biopsy and human studies evidencing improvement in different metabolic parameters and/or steatosis and fibrosis on FibroScan ( < 0.05).
CONCLUSION
The data analyzed in this review showed clinically significant improvement in individual histological features of NAFLD in both animal and human trials for all four classes, as well as good safety profiles ( < 0.05). We believe this compilation of information will have positive clinical implications in obtaining an FDA-approved therapy for NAFLD.
PubMed: 37701920
DOI: 10.4254/wjh.v15.i8.1001 -
Open Heart Nov 2023Clopidogrel is a P2Y inhibitor that has become a mainstay treatment following percutaneous intervention with drug-eluting stent placement to decrease restenosis and its...
INTRODUCTION
Clopidogrel is a P2Y inhibitor that has become a mainstay treatment following percutaneous intervention with drug-eluting stent placement to decrease restenosis and its potential complications, including sudden cardiac death and ischaemic strokes in patients with significant vascular disease.
AREAS COVERED
As a prodrug, the metabolism and efficacy of clopidogrel are contingent on the presence of wild-type CYP450 (CYP2C19) alleles. Genetic polymorphisms and variants are well known to impair its ability to prevent major adverse cardiovascular events in these patients, with inadequate response rates as high as 30% in previous publications. Patterns of allelic frequencies are expected to exhibit similarities between individuals of the same ancestry, ethnic group or geographic region. Accordingly, we seek to further elucidate worldwide prevalence rates for genetic polymorphisms in the CYP2C19-dependent metabolism of clopidogrel and review the potential of personalised CYP2C19 genotyping in clinical practice to mitigate this high treatment resistance and its associated burden on patients.
EXPERTS' COMMENTARY
Our findings support the consideration of genotyping before initiation of therapy to guide adequate dosage or substitutions of other P2Y inhibitors to promote personalised, precision medicine and to prevent adverse events when these therapies may inevitably fail in patients with variants of the CYP450 (CYP2C19) system.
Topics: Humans; Clopidogrel; Platelet Aggregation Inhibitors; Cytochrome P-450 CYP2C19; Drug-Eluting Stents; Polymorphism, Genetic
PubMed: 37963685
DOI: 10.1136/openhrt-2023-002436