-
International Journal of Obesity (2005) Aug 2023Recent studies suggest that tirzepatide, a dual glucose-dependent insulinotropic-peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA), has significant... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recent studies suggest that tirzepatide, a dual glucose-dependent insulinotropic-peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA), has significant weight loss effects. This systematic review and meta-analysis aims to assess the efficacy and safety of tirzepatide for weight loss in patients with overweight or obesity.
METHODS
Medline, Embase and Cochrane CENTRAL were searched for randomized controlled trials (RCTs) on tirzepatide's weight loss efficacy for these patients. A single arm meta-analysis of proportions estimated primary outcomes, ≥5%, ≥10%, and ≥15% weight loss, and adverse events (AEs); while meta-analysis of means estimated secondary outcomes. Comparative meta-analysis was conducted between tirzepatide and control arms where mean differences and odds ratios were estimated for continuous and dichotomous outcomes respectively.
RESULTS
RCTs included in this study revealed that among 5800 patients, 78.22% (95% CI: 72.15% to 83.73%), 55.60% (95% CI: 46.54% to 64.47%), 32.28% (95% CI: 23.17% to 42.12%) achieved ≥5%, ≥10%, and ≥15% weight loss, respectively. Tirzepatide 5 mg demonstrated weight loss superiority relative to placebo (MD: -12.47 kg, 95% CI: -13.94 kg to -11.00 kg) and semaglutide (n = 1409, MD: -1.90 kg, 95% CI: -2.97 kg to -0.83 kg) with dose-dependent increase for 10 mg and 15 mg doses. The comparison between tirzepatide and semaglutide was examined in the SURPASS-2 trial that was included in this systematic review. For AEs, there was increase odds of experiencing gastrointestinal AEs with tirzepatide compared to placebo, but no significant difference with semaglutide.
CONCLUSION
Tirzepatide has significant potential as a weight loss drug in patients with overweight and obesity, with little increase in AEs compared to other weight loss drugs. With its ability to concurrently target multiple aspects of metabolic syndrome, it should be considered as the next helm of weight loss therapies.
Topics: Humans; Overweight; Obesity; Gastric Inhibitory Polypeptide; Anti-Obesity Agents; Weight Loss; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Glucagon-Like Peptide-1 Receptor
PubMed: 37253796
DOI: 10.1038/s41366-023-01321-5 -
Fertility and Sterility Dec 2023The impact of paternal obesity and metabolic disease on semen quality and fertility outcomes is not fully appreciated. With increasing obesity rates, researchers have... (Review)
Review
The impact of paternal obesity and metabolic disease on semen quality and fertility outcomes is not fully appreciated. With increasing obesity rates, researchers have studied the intricate relationship between paternal body mass index, metabolic health, and male fertility. This systematic review identified 112 articles in the MEDLINE database between 2013 and 2023 that investigated the effects of body mass index, diabetes, metabolic syndrome, exercise, weight loss medication, or bariatric surgery on semen parameters, sperm quality, or fertility outcomes. This review suggests that obesity, diabetes, and metabolic syndrome have a negative impact on various parameters of male fertility, from semen quality to sperm deoxyribonucleic acid integrity. There is also mounting evidence that male obesity is correlated negatively with live births via both natural conception and assisted reproductive technologies. Lifestyle interventions, such as physical exercise, generally appear to improve male fertility markers; however, the type and intensity of exercise may play a crucial role. Pharmacologic treatments for weight loss, such as metformin and glucagon-like peptide 1 agonists, present a more complex picture, with studies suggesting both beneficial and detrimental effects on male reproductive health. Similarly, surgical interventions, such as gastric bypass surgery, show promise in improving hormonal imbalances but have mixed effects on semen parameters. Future research is needed to clarify these associations and inform clinical guidelines. In the interim, health practitioners should incorporate these insights into clinical practices, encouraging proactive lifestyle changes and providing targeted treatments to improve male reproductive health.
Topics: Male; Humans; Semen Analysis; Semen; Metabolic Syndrome; Obesity; Infertility, Male; Fertility; Weight Loss; Diabetes Mellitus
PubMed: 37839720
DOI: 10.1016/j.fertnstert.2023.10.017 -
The Journal of Clinical Endocrinology... Dec 2023Polycystic ovary syndrome (PCOS) is a complex genetic trait and the most common endocrine disorder of women, clinically evident in 5% to 15% of reproductive-aged women...
PURPOSE
Polycystic ovary syndrome (PCOS) is a complex genetic trait and the most common endocrine disorder of women, clinically evident in 5% to 15% of reproductive-aged women globally, with associated cardiometabolic dysfunction. Adipose tissue (AT) dysfunction appears to play an important role in the pathophysiology of PCOS even in patients who do not have excess adiposity.
METHODS
We undertook a systematic review concerning AT dysfunction in PCOS, and prioritized studies that assessed AT function directly. We also explored therapies that targeted AT dysfunction for the treatment of PCOS.
RESULTS
Various mechanisms of AT dysfunction in PCOS were identified including dysregulation in storage capacity, hypoxia, and hyperplasia; impaired adipogenesis; impaired insulin signaling and glucose transport; dysregulated lipolysis and nonesterified free fatty acids (NEFAs) kinetics; adipokine and cytokine dysregulation and subacute inflammation; epigenetic dysregulation; and mitochondrial dysfunction and endoplasmic reticulum and oxidative stress. Decreased glucose transporter-4 expression and content in adipocytes, leading to decreased insulin-mediated glucose transport in AT, was a consistent abnormality despite no alterations in insulin binding or in IRS/PI3K/Akt signaling. Adiponectin secretion in response to cytokines/chemokines is affected in PCOS compared to controls. Interestingly, epigenetic modulation via DNA methylation and microRNA regulation appears to be important mechanisms underlying AT dysfunction in PCOS.
CONCLUSION
AT dysfunction, more than AT distribution and excess adiposity, contributes to the metabolic and inflammation abnormalities of PCOS. Nonetheless, many studies provided contradictory, unclear, or limited data, highlighting the urgent need for additional research in this important field.
Topics: Humans; Female; Adult; Polycystic Ovary Syndrome; Insulin Resistance; Phosphatidylinositol 3-Kinases; Adipose Tissue; Insulin; Cytokines; Obesity; Inflammation; Glucose
PubMed: 37329216
DOI: 10.1210/clinem/dgad356 -
Drugs Oct 2023Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy characterized by drug-resistant, lifelong seizures. The management of seizures in DS has... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy characterized by drug-resistant, lifelong seizures. The management of seizures in DS has changed in recent years with the approval of new antiseizure medications (ASMs).
OBJECTIVE
The aim of this study was to estimate the comparative efficacy and tolerability of the ASMs for the treatment of seizures associated with DS using a network meta-analysis (NMA).
METHODS
Studies were identified by conducting a systematic search (week 4, January 2023) of the MEDLINE (accessed by PubMed), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and US National Institutes of Health Clinical Trials Registry ( http://www.
CLINICALTRIALS
gov ) databases. Any randomized, controlled, double- or single-blinded, parallel-group study comparing at least one ASM therapy against placebo, another ASM, or a different dose of the same ASM in participants with a diagnosis of DS was identified. The efficacy outcomes were the proportions of participants with ≥ 50% (seizure response) and 100% reduction (seizure freedom) in baseline convulsive seizure frequency during the maintenance period. The tolerability outcomes included the proportions of patients who withdrew from treatment for any reason and who experienced at least one adverse event (AE). Effect sizes were estimated by network meta-analyses within a frequentist framework.
RESULTS
Eight placebo-controlled trials were included, and the active add-on treatments were stiripentol (n = 2), pharmaceutical-grade cannabidiol (n = 3), fenfluramine hydrochloride (n = 2), and soticlestat (n = 1). The studies recruited 680 participants, of whom 409 were randomized to active treatments (stiripentol = 33, pharmaceutical-grade cannabidiol = 228, fenfluramine hydrochloride = 122, and soticlestat = 26) and 271 to placebo. Pharmaceutical-grade cannabidiol was associated with a lower rate of seizure response than fenfluramine hydrochloride (odds ratio [OR] 0.20, 95% confidence interval [CI] 0.07-0.54), and stiripentol was associated with a higher seizure response rate than pharmaceutical-grade cannabidiol (OR 14.07, 95% CI 2.57-76.87). No statistically significant differences emerged across the different ASMs for the seizure freedom outcome. Stiripentol was associated with a lower probability of drug discontinuation for any reason than pharmaceutical-grade cannabidiol (OR 0.45, 95% CI 0.04-5.69), and pharmaceutical-grade cannabidiol was associated with a lower proportion of participants experiencing any AE than fenfluramine hydrochloride (OR 0.22, 95% CI 0.06-0.78). Stiripentol had a higher risk of AE occurrence than pharmaceutical-grade cannabidiol (OR 75.72, 95% CI 3.59-1598.58). The study found high-quality evidence of efficacy and tolerability of the four ASMs in the treatment of convulsive seizures in DS.
CONCLUSIONS
There exists first-class evidence that documents the efficacy and tolerability of stiripentol, pharmaceutical-grade cannabidiol, fenfluramine hydrochloride, and soticlestat for the treatment of seizures associated with DS, and allows discussion about the expected outcomes regarding seizure frequency reduction and tolerability profiles.
Topics: Humans; Anticonvulsants; Cannabidiol; Network Meta-Analysis; Randomized Controlled Trials as Topic; Seizures; Epilepsies, Myoclonic; Fenfluramine; Pharmaceutical Preparations
PubMed: 37695433
DOI: 10.1007/s40265-023-01936-y -
International Journal of Nursing Studies Oct 2023The association between sedentary behavior and health-related outcomes has been well established, whereas it is inconclusive whether a sedentary behavior pattern is an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The association between sedentary behavior and health-related outcomes has been well established, whereas it is inconclusive whether a sedentary behavior pattern is an additional risk factor for health-related outcomes independent of total sedentary time and physical activity.
OBJECTIVES
To determine sedentary behavior patterns and their association with risks of noncommunicable diseases and all-cause mortality and to assess whether this association is independent of total sedentary time and physical activity.
DESIGN
This was a systematic review and meta-analysis.
METHODS
Studies were obtained by searching the Web of Science Core Collection, PubMed/Medline, the Cochrane Library, Embase, CINAHL, and SPORTDiscus up to April 2023. All observational studies published in English or Chinese were included if they explored sedentary behavior patterns and their association with risks of abdominal obesity, metabolic syndrome, diabetes, cardiovascular disease, cancer, and all-cause mortality among individuals who had never experienced the outcome event before the baseline assessment. Data extraction using a standardized form and quality appraisal using two authoritative tools were then performed. All these steps were completed by two independent reviewers from December 2022 to May 2023. If data were sufficiently homogenous, meta-analyses were performed; otherwise, narrative syntheses were employed. Harvest plots were also used to visually represent the distribution of evidence.
RESULTS
Eighteen studies comprising 11 prospective cohort studies and seven cross-sectional studies were included. The findings suggested that prolonged sedentary time and usual sedentary bout duration were two metrics that reflected the nonlinear dose-response effect of prolonged sedentary behavior patterns. Only extremely high levels of prolonged sedentary behavior patterns significantly increased the risk of adverse health outcomes, independent of physical activity. Whether prolonged sitting was an additional risk factor for adverse health outcomes, independent of total sedentary time, was inconclusive due to an insufficient number of primary studies that included total sedentary time as one of the potential covariates. There was some evidence that supported a sedentary bout that significantly increased the risk of adverse health outcomes was 30-60 min. The threshold of prolonged sedentary time differed with outcomes, and future studies are needed to make this threshold more precise.
CONCLUSION
A prolonged sedentary behavior pattern was associated with increased risks of several major noncommunicable diseases and all-cause mortality. People, especially those who do not reach the recommended level of moderate-to-vigorous physical activity, are encouraged to interrupt sedentary bouts every 30 to 60 min and limit prolonged sedentary time per day as much as possible.
TWEETABLE ABSTRACT
Breaking up consecutive sedentary bouts >30 to 60 min and substituting them with brief bouts of physical activity.
Topics: Humans; Sedentary Behavior; Noncommunicable Diseases; Prospective Studies; Cross-Sectional Studies; Exercise
PubMed: 37523952
DOI: 10.1016/j.ijnurstu.2023.104563 -
Irish Journal of Medical Science Dec 2023Polycystic Ovary Syndrome is the most prevalent hormonal disorder in females. Over the years, metformin (MET) has become the first-line choice of treatment; however, due... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Polycystic Ovary Syndrome is the most prevalent hormonal disorder in females. Over the years, metformin (MET) has become the first-line choice of treatment; however, due to its gastrointestinal side effects, a more recent drug, myo-inositol (MI), has been introduced. We aim to conduct a systematic review and meta-analysis to compare the effects of MET and MI on hormonal and metabolic parameters.
MATERIALS AND METHODS
Authors extensively searched PubMed, Scopus, Cochrane Library, Google Scholar, and Web of Science for randomized clinical trials (RCTs) until August 2021. Eight (n = 8) articles were included, with a total sample size of 1088, of which 460 patients received MET, 436 received MI, and 192 received a combination of both. Standard mean differences (SMDs) and Confidence Intervals (CIs) were used for data synthesis, and forest plots were made using Review Manager 5.4 for Statistical Analysis using the random-effect model.
RESULTS
The meta-analysis indicates that there is no significant difference between MET and MI in terms of their effects on BMI (SMD = 0.16, 95% CI: - 0.11 to 0.43, p = 0.24), fasting insulin (SMD = 0.00, 95% CI: - 0.26 to 0.27, p = 0.97), fasting blood sugar (SMD = 0.11, 95% CI: - 0.31to 0.53, p = 0.60), HOMA index (SMD = 0.09, 95% CI: - 0.20 to 0.39, p = 0.50), and LH/FSH (SMD = 0.20, 95% CI: - 0.24 to 0.64, p = 0.37). BMI, fasting blood sugar, and LH/FSH ratio reported moderate heterogeneity because of the varying number of study participants.
CONCLUSION
Our meta-analysis comparing hormonal and metabolic parameters between MET and MI did not show much significant difference, indicating both drugs are equally beneficial in improving metabolic and hormonal parameters in patients with PCOS.
Topics: Female; Humans; Metformin; Polycystic Ovary Syndrome; Hypoglycemic Agents; Blood Glucose; Inositol; Follicle Stimulating Hormone
PubMed: 37148410
DOI: 10.1007/s11845-023-03388-5 -
The Journal of Clinical Endocrinology... May 2024Insulin resistance is common in women with polycystic ovary syndrome (PCOS). Inositol may have insulin sensitizing effects; however, its efficacy in the management of... (Meta-Analysis)
Meta-Analysis
CONTEXT
Insulin resistance is common in women with polycystic ovary syndrome (PCOS). Inositol may have insulin sensitizing effects; however, its efficacy in the management of PCOS remains indeterminate.
OBJECTIVE
To inform the 2023 international evidence-based guidelines in PCOS, this systematic review and meta-analysis evaluated the efficacy of inositol, alone or in combination with other therapies, in the management of PCOS.
DATA SOURCES
Medline, PsycInfo, EMBASE, All EBM, and CINAHL from inception until August 2022.
STUDY SELECTION
Thirty trials (n = 2230; 1093 intervention, 1137 control), with 19 pooled in meta-analyses were included.
DATA EXTRACTION
Data were extracted for hormonal, metabolic, lipids, psychological, anthropometric, reproductive outcomes, and adverse effects by 1 reviewer, independently verified by a second.
DATA SYNTHESIS
Thirteen comparisons were assessed, with 3 in meta-analyses. Evidence suggests benefits for myo-inositol or D-chiro-inositol (DCI) for some metabolic measures and potential benefits from DCI for ovulation, but inositol may have no effect on other outcomes. Metformin may improve waist-hip ratio and hirsutism compared to inositol, but there is likely no difference for reproductive outcomes, and the evidence is very uncertain for body mass indexI. Myo-inositol likely causes fewer gastrointestinal adverse events compared with metformin; however, these are typically mild and self-limited.
CONCLUSION
The evidence supporting the use of inositol in the management of PCOS is limited and inconclusive. Clinicians and their patients should consider the uncertainty of the evidence together with individual values and preferences when engaging in shared decision-making regarding the use of inositol for PCOS.
Topics: Polycystic Ovary Syndrome; Humans; Inositol; Female; Practice Guidelines as Topic; Insulin Resistance; Evidence-Based Medicine
PubMed: 38163998
DOI: 10.1210/clinem/dgad762 -
Environmental Pollution (Barking, Essex... Sep 2023Phthalates are chemicals widely used in plastic-based consumer products, and human exposure is universal. They are classified as endocrine disruptors, and specific... (Meta-Analysis)
Meta-Analysis Review
Phthalates are chemicals widely used in plastic-based consumer products, and human exposure is universal. They are classified as endocrine disruptors, and specific phthalate metabolites have been associated with an increased risk of cardiometabolic diseases. The aim of this study was to assess the association between phthalate exposure and the metabolic syndrome in the general population. A comprehensive literature search was performed in four databases (Web of Science, Medline, PubMed, and Scopus). We included all the observational studies that evaluate the association between phthalate metabolites and the metabolic syndrome available until January 31st, 2023. Pooled Odds Ratios (OR) and their 95% confidence intervals were calculated by using the inverse-variance weighted method. Nine cross-sectional studies and 25,365 participants aged from 12 to 80 were included. Comparing extreme categories of phthalate exposure, the pooled ORs for the metabolic syndrome were: 1.08 (95% CI, 1.02-1.16, I = 28%) for low molecular weight phthalates, and 1.11 (95% CI, 1.07-1.16, I = 7%) for high molecular weight phthalates. For individual phthalate metabolites, the pooled ORs that achieved statistical significance were: 1.13 (95% CI, 1.00-1.27, I = 24%) for MiBP; 1.89 (95% CI, 1.17-3.07, I = 15%) for MMP in men; 1.12 (95% CI, 1.00-1.25, I = 22%) for MCOP; 1.09 (95% CI, 0.99-1.20, I = 0%) for MCPP; 1.16 (95% CI, 1.05-1.28, I = 6%) for MBzP; and 1.16 (95% CI, 1.09-1.24, I = 14%) for DEHP (including ΣDEHP and its metabolites). In conclusion, both low molecular weight and high molecular weight phthalates were associated with an 8 and 11% higher prevalence of the MetS, respectively. The exposure to six specific phthalate metabolites was associated with a higher prevalence of the MetS.
Topics: Male; Humans; Metabolic Syndrome; Environmental Pollutants; Cross-Sectional Studies; Phthalic Acids; Plastics; Environmental Exposure
PubMed: 37328121
DOI: 10.1016/j.envpol.2023.121957 -
Diabetology & Metabolic Syndrome Oct 2023Metabolic syndrome (MetS) is a group of metabolic abnormalities characterised by hypertension, central obesity, dyslipidaemia and dysregulation of blood glucose,... (Review)
Review
BACKGROUND
Metabolic syndrome (MetS) is a group of metabolic abnormalities characterised by hypertension, central obesity, dyslipidaemia and dysregulation of blood glucose, associated with the risk of diabetes, cardiovascular disease and overall mortality. The presence of elevated liver enzymes may precede the development of MetS, with alterations of the liver being observed that are directly related to metabolic problems. The study aims to provide the best evidence on the association between liver enzymes (ALT, AST, GGT) and MetS by determining the effect size of these biomarkers.
METHODS
A systematic review and meta-analysis of studies indexed in PubMed and Scopus databases were performed. Study quality was assessed using the STROBE tool. The Grade Pro tool was used to evaluate the evidence, and the quantitative synthesis was performed using RevMan (Cochrane Collaboration).
RESULTS
Seventeen articles comparing liver enzyme concentrations between 76,686 with MetS (MetS+) and 201,855 without MetS (MetS-) subjects were included. The concentration of ALT, AST and GGT in the MetS + subjects was significantly higher than in the control group 7.13 IU/L (CI95% 5.73-8.54; p < 0.00001; I = 96%), 2.68 IU/L (CI95% 1.82-3.54; p < 0.00001; I = 96%) and 11.20 IU/L (CI95% 7.11-15.29; p < 0.00001; I = 96%), respectively.
CONCLUSIONS
The evaluation of the relationship of liver enzymes in the pathophysiological process of MetS could lead to new insights into early diagnosis.
PubMed: 37899468
DOI: 10.1186/s13098-023-01200-z -
Journal of the American Association of... Aug 2023Psyllium is a natural, predominantly soluble fiber that forms a viscous gel when hydrated and is not digested or fermented. In the small intestine, psyllium gel... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Psyllium is a natural, predominantly soluble fiber that forms a viscous gel when hydrated and is not digested or fermented. In the small intestine, psyllium gel increases chyme viscosity, slowing the degradation and absorption of nutrients. Psyllium has a significant effect in patients with metabolic syndrome and type-2 diabetes on glycemic control, while lowering serum cholesterol in hypercholesterolemic patients. Some randomized controlled studies have shown that psyllium also facilitates weight loss in overweight and obese participants.
OBJECTIVES
A comprehensive review and meta-analysis assessing psyllium's impact on body weight, body mass index (BMI), and waist circumference in overweight and obese participants.
DATA SOURCES
A comprehensive search was performed (Medline, Scopus, Cochrane Database) through March 21, 2022, using search terms to identify randomized, controlled, clinical studies designed to assess weight loss in overweight and obese participants over at least 2 months. Data were analyzed using the inverse variance method with random effects models.
CONCLUSIONS
Six studies meeting inclusion criteria were identified (total n = 354). The meta-analysis showed that psyllium, dosed just before meals (mean dose 10.8 g/day, mean duration 4.8 months), was effective for decreasing body weight (MD = -2.1 kg [95% confidence interval [CI]: -2.6 to -1.6]; p < .001), BMI (MD = -0.8 kg/m 2 [95% CI: -1.0 to -0.6]; p < .001) and waist circumference (MD = -2.2 cm [95% CI: -2.9 to -1.4]; p < .001) in overweight and obese populations.
IMPLICATIONS FOR PRACTICE
Gel-forming nonfermented psyllium fiber, dosed just before meals, is effective in facilitating weight loss in overweight and obese participants.
Topics: Humans; Body Weight; Obesity; Overweight; Psyllium; Weight Loss
PubMed: 37163454
DOI: 10.1097/JXX.0000000000000882