-
Obesity Reviews : An Official Journal... Jun 2022Clinical trials have investigated the weight loss effect of glucagon-like peptide-1 receptor agonists (GLP-1 RA) in adults with obesity without diabetes mellitus, but... (Meta-Analysis)
Meta-Analysis Review
Effect of glucagon-like peptide-1 receptor agonists on body weight in adults with obesity without diabetes mellitus-a systematic review and meta-analysis of randomized control trials.
Clinical trials have investigated the weight loss effect of glucagon-like peptide-1 receptor agonists (GLP-1 RA) in adults with obesity without diabetes mellitus, but results for weight loss efficacy were varied. We aimed to provide an up-to-date systematic review and meta-analysis for overall weight loss effect of GLP-1 RA in adults with obesity and overweight without diabetes mellitus. We retrieved eligible randomized control trials that assessed the weight loss effect of GLP-1 RA in adults (≥18 years old) without type 1/type 2 diabetes up to September 30, 2021, using Pubmed and Embase. Of 36 clinical trials assessed for eligibility, 12 trials were included, with a combined total of 11,459 participants. Compared with control groups, a more significant weight loss was seen in GLP-1 RA groups with an overall mean difference of -7.1 kg (95% CI -9.2 to -5.0) (I = 99%). The overall analysis results showed that GLP-1 RA improved glycemic control without increasing the risk of hypoglycemic events. Better control of blood pressure and plasma levels of LDL, HDL, and triglycerides was seen with GLP-1 RA treatment. Subgroup analysis showed greater treatment effect of semaglutide than liraglutide. Vomiting, nausea, dyspepsia, diarrhea, constipation, and abdominal pain were GLP-1 RA-associated common adverse effects.
Topics: Adolescent; Adult; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Obesity; Weight Loss
PubMed: 35194917
DOI: 10.1111/obr.13435 -
Obesity Reviews : An Official Journal... Mar 2021This systematic review and meta-analysis investigated the association between consumption of ultraprocessed food and noncommunicable disease risk, morbidity and... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis investigated the association between consumption of ultraprocessed food and noncommunicable disease risk, morbidity and mortality. Forty-three observational studies were included (N = 891,723): 21 cross-sectional, 19 prospective, two case-control and one conducted both a prospective and cross-sectional analysis. Meta-analysis demonstrated consumption of ultraprocessed food was associated with increased risk of overweight (odds ratio: 1.36; 95% confidence interval [CI], 1.23-1.51; P < 0.001), obesity (odds ratio: 1.51; 95% CI, 1.34-1.70; P < 0.001), abdominal obesity (odds ratio: 1.49; 95% CI, 1.34-1.66; P < 0.0001), all-cause mortality (hazard ratio: 1.28; 95% CI, 1.11-1.48; P = 0.001), metabolic syndrome (odds ratio: 1.81; 95% CI, 1.12-2.93; P = 0.015) and depression in adults (hazard ratio: 1.22; 95% CI, 1.16-1.28, P < 0.001) as well as wheezing (odds ratio: 1.40; 95% CI, 1.27-1.55; P < 0.001) but not asthma in adolescents (odds ratio: 1.20; 95% CI, 0.99-1.46; P = 0.065). In addition, consumption of ultraprocessed food was associated with cardiometabolic diseases, frailty, irritable bowel syndrome, functional dyspepsia and cancer (breast and overall) in adults while also being associated with metabolic syndrome in adolescents and dyslipidaemia in children. Although links between ultraprocessed food consumption and some intermediate risk factors in adults were also highlighted, further studies are required to more clearly define associations in children and adolescents. STUDY REGISTRATION: Prospero ID: CRD42020176752.
Topics: Adolescent; Adult; Child; Cross-Sectional Studies; Food; Food Handling; Humans; Noncommunicable Diseases; Observational Studies as Topic; Prospective Studies
PubMed: 33167080
DOI: 10.1111/obr.13146 -
Alimentary Pharmacology & Therapeutics Jan 2021Functional dyspepsia (FD) is a relapsing and remitting condition affecting between 5% and 10% of people. Efficacious therapies are available, but their relative efficacy... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Functional dyspepsia (FD) is a relapsing and remitting condition affecting between 5% and 10% of people. Efficacious therapies are available, but their relative efficacy is unknown.
AIM
To perform a systematic review with network meta-analysis to resolve this uncertainty.
METHODS
We searched the medical literature through July 2020 for randomised controlled trials (RCTs) assessing efficacy of drugs for adults with FD, compared with each other, or placebo. Trials reported a dichotomous assessment of symptom status after completion of therapy. We pooled data using a random effects model. Efficacy was reported as a pooled relative risk (RR) of remaining symptomatic with a 95% confidence interval (CI) to summarise efficacy of each comparison tested. Relative ranking was assessed with surface under the cumulative ranking curve (SUCRA) probabilities.
RESULTS
We identified 71 eligible RCTs (19 243 participants). Tricyclic antidepressants (TCAs) were ranked second for efficacy (RR of remaining symptomatic = 0.71; 95% CI 0.58-0.87, SUCRA 0.87), and first when only low risk of bias trials were included. Most RCTs that used TCAs recruited patients who were refractory to other drugs included in the network. Although sulpiride or levosulpiride were ranked first for efficacy (RR = 0.49; 95% CI 0.36-0.69, SUCRA 0.99), trial quality was low and only 86 patients received active therapy. TCAs were more likely to cause adverse events than placebo.
CONCLUSIONS
TCAs, histamine- receptor antagonists, standard- and low-dose proton pump inhibitors, sulpiride or levosulpiride, itopride and acotiamide were all more efficacious than placebo for FD.
Topics: Adult; Dyspepsia; Histamine H2 Antagonists; Humans; Network Meta-Analysis; Pharmaceutical Preparations; Proton Pump Inhibitors
PubMed: 32936964
DOI: 10.1111/apt.16072 -
Nutrients Jan 2020Probiotic is little known for its benefits on upper gastrointestinal health. The objective of this systematic review was to examine the efficacy of probiotics in...
Probiotic is little known for its benefits on upper gastrointestinal health. The objective of this systematic review was to examine the efficacy of probiotics in alleviating the frequency and severity of symptoms in gastroesophageal reflux disease (GERD) in the general adult population. The PubMed and Web of Science databases were searched for prospective studies on GERD, heartburn, regurgitation, and dyspepsia, without any limitation on sample size. The Jadad scale was used to evaluate the quality of randomized controlled trials. In total, 13 prospective studies that were published in 12 articles were included in the analysis and scored per the Jadad scale as high- (five studies), medium- (two), and low- (six) quality. One article reported on two probiotic groups; thus, 14 comparisons were included in the selected studies, of which 11 (79%) reported positive benefits of probiotics on symptoms of GERD. Five out of 11 positive outcomes (45%) noted benefits on reflux symptoms: three noted reduced regurgitation; improvements in reflux or heartburn were seen in one study; five (45%) saw improvements in dyspepsia symptoms; and nine (81%) saw improvements in other upper gastrointestinal symptoms, such as nausea (three studies), abdominal pain (five), and gas-related symptoms (four), such as belching, gurgling, and burping. In conclusion, probiotic use can be beneficial for GERD symptoms, such as regurgitation and heartburn. However, proper placebo-controlled, randomized, and double-blinded clinical trials with a sufficient number of participants are warranted to confirm its efficacy in alleviating these symptoms. Further, interventions with longer durations and an intermediate analysis of endpoints should be considered to determine the proper therapeutic window.
Topics: Gastroesophageal Reflux; Humans; Probiotics
PubMed: 31906573
DOI: 10.3390/nu12010132 -
Journal of Gastroenterology and... Sep 2022Hypermobile Ehlers-Danlos syndrome (hEDS) and the hypermobility spectrum disorders (HSD) can be challenging to diagnose and manage. Gastrointestinal symptoms and... (Review)
Review
BACKGROUND AND AIM
Hypermobile Ehlers-Danlos syndrome (hEDS) and the hypermobility spectrum disorders (HSD) can be challenging to diagnose and manage. Gastrointestinal symptoms and disorders of gut-brain interaction are common in this cohort and multifactorial in origin. The primary aim of this review is to arm the gastroenterologist with a clinically useful understanding of HSD/hEDS, by exploring the association of gastrointestinal disorders with HSD/hEDS, highlighting current pathophysiological understanding and providing a pragmatic approach to managing these patients.
METHODS
Literature relevant to the gastrointestinal system and hypermobile Ehlers-Danlos syndrome was systematically searched, critically appraised, and summarized.
RESULTS
Diagnosis is based upon clinical criteria and a genetic basis is yet to be defined. The prevalence of many gut symptoms, including abdominal pain (69% vs 27%, P < 0.0001), postprandial fullness (34% vs 16%, P = 0.01), constipation (73% vs 16%, P < 0.001), and diarrhea (47% vs 9%, P < 0.001) are significantly higher in HSD/hEDS compared with non-HSD/hEDS individuals. Disorders of gut-brain interaction are also common, particularly functional dyspepsia. The pathophysiology of gut symptoms is poorly understood but may involve effects of connective tissue laxity and its functional consequences, and the influence of autonomic dysfunction, medication and comorbid mental health disorders. Awareness is the key to early diagnosis. Management is limited in evidence-base but ideally should include an integrated multidisciplinary approach.
CONCLUSIONS
HSD/hEDS is a multisystemic disorder in which gastrointestinal symptoms, particularly related to disorders of gut-brain interaction are common. Deficiencies in knowledge regarding the pathophysiological processes limit evidence-based interventions and remain important areas for future research.
Topics: Ehlers-Danlos Syndrome; Gastroenterologists; Gastrointestinal Diseases; Humans; Joint Instability
PubMed: 35750466
DOI: 10.1111/jgh.15927 -
Contemporary Clinical Trials... Aug 2022Semaglutide is a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) indicated for glycaemic management in adults with type 2 diabetes (T2D). Oral... (Review)
Review
The efficacy and safety of oral semaglutide for glycaemic management in adults with type 2 diabetes compared to subcutaneous semaglutide, placebo, and other GLP-1 RA comparators: A systematic review and network meta-analysis.
AIM
Semaglutide is a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) indicated for glycaemic management in adults with type 2 diabetes (T2D). Oral semaglutide administration can help decrease glycated haemoglobin (HbA1c) and body weight in people with uncontrolled T2D. We evaluated the efficacy and safety of oral semaglutide compared to that of subcutaneous semaglutide, placebo, and other GLP-1 RAs in the treatment of T2D.
METHODS
Randomised controlled trials of subcutaneous and oral semaglutide for glycaemic control in adults with T2D were selected from the Cochrane Central Register of Controlled Trials and PubMed. Mean differences (MDs) and risk ratios with 95% confidence intervals (CIs) were used to synthesise the results, and oral and subcutaneous semaglutide formulations were indirectly compared using mixed treatment comparisons.
RESULTS
Twelve studies were included in this review (6840 participants). Oral semaglutide (14.0 mg) significantly reduced HbA1c (MD, -1.30% [95%CI: -1.44, -1.16], P < 0.05) and body weight (MD, -3.17 kg [95%CI: -3.89, -2.45], P < 0.05) compared to placebo (MD, HbA1c: -0.32% [95%CI: -0.49, -0.15], P < 0.05; MD body weight: -2.56 kg [95%CI: -3.41, -1.71], P < 0.05), liraglutide (1.2 mg), exenatide ER (2.0 mg), and dulaglutide (1.5 mg). Oral semaglutide was slightly less effective than subcutaneous semaglutide in reducing HbA1c levels (MD: -0.26% [95%CI: -0.44, -0.07], P < 0.05) and body weight (MD: -1.08 kg [95%CI: -2.04, -0.12], P < 0.05). Oral semaglutide increased the incidence of adverse events (nausea, diarrhoea, dyspepsia, and vomiting) compared to placebo, liraglutide (1.2 mg), exenatide (ER, 2.0 mg), and dulaglutide 1.5 mg but not compared to subcutaneous semaglutide.
CONCLUSION
Oral semaglutide was non-inferior to subcutaneous semaglutide and superior to placebo and another GLP-1 RA in reducing HbA1c and body weight. It was superior to subcutaneous semaglutide and inferior to other GLP-1 RA comparators and placebo in terms of the incidence of adverse events. Thus, oral semaglutide provides a convenient administration route for patients who prefer oral treatments over injectable therapies.
PubMed: 35812819
DOI: 10.1016/j.conctc.2022.100944 -
Progress in Neuro-psychopharmacology &... Jul 2021Gastrointestinal side effects (SEs) are frequently observed in patients with major depressive disorder (MDD) while taking antidepressants and may lead to treatment... (Meta-Analysis)
Meta-Analysis
Gastrointestinal side effects (SEs) are frequently observed in patients with major depressive disorder (MDD) while taking antidepressants and may lead to treatment discontinuation. The aim of this meta-analysis is to provide quantitative measures on short-term rates of gastrointestinal SEs in MDD patients treated with second-generation antidepressants. An electronic search of the literature was conducted by using MEDLINE, ISI Web of Science - Web of Science Core Collection, and Cochrane Library databases. Eligible studies had to focus on the use of at least one of 15 antidepressants commonly used in MDD (i.e., agomelatine, bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, mirtazapine, paroxetine, reboxetine, sertraline, venlafaxine, and vortioxetine) and report data on treatment-emergent gastrointestinal SEs (i.e. nausea/vomiting, diarrhoea, constipation, abdominal pain, dyspepsia, anorexia, increased appetite and dry mouth) within 12 weeks of treatment. Overall, 304 studies were included in the meta-analyses. All the considered antidepressants showed higher rates of gastrointestinal SEs than placebo. Escitalopram and sertraline were shown to be the least tolerated antidepressants on the gastrointestinal tract, being associated with all the considered SEs with the exception of constipation and increased appetite, while mirtazapine was shown to be the antidepressant with fewer side effects on the gut, being only associated with increased appetite. In conclusion, commonly used antidepressants showed different profiles of gastrointestinal SEs, possibly related to their mechanisms of action. The specific tolerability profile of each compound should be considered by clinicians when prescribing antidepressants in order to improve adherence to treatment and increase positive outcomes in patients with MDD.
Topics: Antidepressive Agents; Constipation; Depressive Disorder, Major; Diarrhea; Humans; Nausea; Vomiting
PubMed: 33549697
DOI: 10.1016/j.pnpbp.2021.110266 -
Diabetes & Metabolic Syndrome Oct 2023This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of 24 weeks of semaglutide treatment in patients with non-alcoholic fatty... (Meta-Analysis)
Meta-Analysis Review
AIM
This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of 24 weeks of semaglutide treatment in patients with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH).
METHODS
PubMed, Embase, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov databases were searched for relevant studies. The primary outcome was the change in the serum alanine transaminase level. The secondary outcomes were changes in liver stiffness, liver function test parameters, metabolic parameters, and safety. Pooled mean differences and relative risks were calculated using random-effects models.
RESULTS
Six hundred studies were screened and eight were included (n = 2413). Semaglutide treatment showed a reduction in serum alanine transaminase [mean difference: 14.07 U/L (95% CI: 19.39 to -8.75); p < 0.001] and aspartate transaminase [mean difference: 6.89 U/L (95% CI: 9.14 to -4.63); p < 0.001] levels. There was a significant improvement in liver fat content [mean difference: 4.97% (95% CI: 6.65 to -3.29); p < 0.001] and liver stiffness [mean difference: 0.96 kPa (95% CI: 1.87 to -0.04); p = 0.04]. There were significant improvements in the glycated hemoglobin level and the lipid profile. However, the risk of serious adverse events [relative risk: 1.54 (95% CI: 1.02 to 2.34); p = 0.04] was high following semaglutide treatment as compared to placebo; the most common ones were gastrointestinal (nausea and vomiting, dyspepsia, decreased appetite, constipation, and diarrhea) and gallbladder-related diseases.
CONCLUSION
Treatment with 24 weeks of semaglutide could significantly improve liver enzymes, reduce liver stiffness, and improve metabolic parameters in patients with NAFLD/NASH. However, the gastrointestinal adverse effects could be a major concern.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Alanine Transaminase; Liver; Glucagon-Like Peptides
PubMed: 37717295
DOI: 10.1016/j.dsx.2023.102849 -
The Lancet. Gastroenterology &... Jul 2023Rome criteria differentiate distinct types of disorders of gut-brain interaction (DGBI); also known as functional gastrointestinal disorders. Overlap of symptom... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Rome criteria differentiate distinct types of disorders of gut-brain interaction (DGBI); also known as functional gastrointestinal disorders. Overlap of symptom categories frequently occurs. This systematic review and meta-analysis aimed to define the prevalence of DGBI overlap and compare overlap in population-based, primary care or tertiary care health settings. Furthermore, we aimed to compare symptom severity of psychological comorbidities in DGBI with and without overlap.
METHODS
For this systematic review and meta-analysis we searched MEDLINE (PubMed) and Embase electronic databases from inception until March 1, 2022, for original articles and conference abstracts of observational cross-sectional, case-controlled, or cohort design studies that reported the prevalence of DGBI overlap in adult participants (aged ≥18 years). We included only those studies where the diagnosis of DGBI was based on clinical assessment, questionnaire data, or specific symptom-based criteria. Studies were excluded if reporting on mixed populations of DGBI and organic diseases. Aggregate patient data were extracted from eligible published studies. The prevalence of DGBI overlap in all studies was pooled using the DerSimonian and Laird random effects model, and further analysis stratified by subgroups (care setting, diagnostic criteria, geographic region, and gross domestic product per capita). We also assessed the relationship between DGBI overlap with anxiety, depression, and quality of life symptom scores. This study was registered with PROSPERO (CRD42022311101).
FINDINGS
46 of 1268 screened studies, reporting on 75 682 adult DGBI participants, were eligible for inclusion in this systematic review and meta-analysis. Overall, 24 424 (pooled prevalence 36·5% [95% CI 30·7 to 42·6]) participants had a DGBI overlap, with considerable between-study heterogeneity (I=99·51, p=0·0001). In the tertiary health-care setting, overlap among participants with DGBI was more prevalent (8373 of 22 617, pooled prevalence 47·3% [95% CI 33·2 to 61·7]) compared with population-based cohorts (11 332 of 39 749, pooled prevalence 26·5% [95% CI 20·5 to 33·4]; odds ratio 2·50 [95% CI 1·28 to 4·87]; p=0·0084). Quality of life physical component scores were significantly lower in participants with DGBI overlap compared with participants without overlap (standardised mean difference -0·47 [95% CI -0·80 to -0·14]; p=0·025). Participants with DGBI overlap had both increased symptom scores for anxiety (0·39 [95% CI 0·24 to 0·54]; p=0·0001) and depression (0·41 [0·30 to 0·51]; p=0·0001).
INTERPRETATION
Overlap of DGBI subtypes is frequent, and is more prevalent in tertiary care settings and associated with more severe symptom manifestations or psychological comorbidities. Despite the large sample size, the comparative analyses revealed substantial heterogeneity, and the results should be interpreted with caution.
FUNDING
National Health and Medical Research Council and Centre for Research Excellence.
Topics: Adult; Humans; Adolescent; Cross-Sectional Studies; Quality of Life; Anxiety; Comorbidity; Brain; Observational Studies as Topic
PubMed: 37211024
DOI: 10.1016/S2468-1253(23)00102-4 -
Nutrients Jun 2023Functional gastrointestinal disorders (FGIDs) are common in children and adolescents. In recent years, interest in the role of diet in the treatment of FGIDs has... (Review)
Review
Functional gastrointestinal disorders (FGIDs) are common in children and adolescents. In recent years, interest in the role of diet in the treatment of FGIDs has increased. Currently, interest focuses on the low-FODMAP diet (LFD), the fructose- or lactose-restricted diet (FRD or LRD), the gluten-free diet (GFD), and the Mediterranean diet (MD). In this review, we focus on the role of these dietary patterns in the FGIDs most commonly diagnosed in clinical practice, namely irritable bowel syndrome (IBS), functional abdominal pain (FAP), functional dyspepsia (FD), and functional constipation (FC). Fifteen clinical trials were systematically reviewed (both RCTs and single-arm clinical trials). We demonstrated the lack of high-quality intervention trials. Based on current evidence, low-FODMAP diet, LRD, FRD, and GFD have no place in daily clinical practice for the management of children and adolescents with FGIDs. Nevertheless, some patients with IBS or RAP may experience some benefit from the use of a low-FODMAP diet or FRD/LRD. Limited data suggest that MD may be promising in the management of FGIDs, especially in IBS patients, but more data are required to investigate the mechanisms of its protective effects.
Topics: Humans; Child; Adolescent; Irritable Bowel Syndrome; Gastrointestinal Diseases; Abdominal Pain; Diet, Gluten-Free; Constipation; Fermentation; Diet, Carbohydrate-Restricted; Monosaccharides
PubMed: 37375612
DOI: 10.3390/nu15122708