Weight Reduction Research Articles

Pharmacological management of pediatric metabolic dysfunction-associated steatotic liver disease.

Pediatric obesity, characterized by a body mass index (BMI) at or above the 95th percentile for age, affects a substantial number of children and adolescents worldwide. Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease, represents a prominent hepatic manifestation of obesity and metabolic syndrome, emerging as the most prevalent hepatic disorder among pediatric patients and a significant contributor to liver transplantation in adults. The escalating prevalence of pediatric MASLD mirrors the alarming rise in childhood obesity rates over recent decades. While lifestyle modifications focusing on dietary changes and increased physical activity constitute the cornerstone of MASLD management, achieving and maintaining significant weight reduction remains challenging. Moreover, disease progression often persists despite standard-of-care interventions, warranting exploration into alternative therapeutic strategies. Pharmacological interventions, particularly, glucagon-like peptide-1 receptor agonists (GLP-1RA), have shown promise in addressing pediatric obesity and its associated comorbidities, including MASLD. Recent studies have demonstrated the efficacy of GLP-1RA in inducing weight loss and improving liver enzyme levels, suggesting a potential role in halting disease progression, and reducing the risk of major adverse liver outcomes. This review provides a comprehensive overview of the current pharmacotherapy landscape for pediatric MASLD, with a focus on novel agents such as GLP-1RA. Furthermore, the manuscript proposes a practical algorithm to assist in integrating GLP-1RA into the clinical management of pediatric patients with obesity and MASLD. Despite promising results, further research is warranted to elucidate the long-term efficacy and safety of GLP-1RA in pediatric populations.

Characterization of the species of Pythium associated with corn seedlings in Delaware.

Corn (Zea mays L.) is the top grain crop by hectares grown in Delaware (DE). Increased pre- and post-emergence damping-off in corn caused by Pythium species have been observed in recent seasons. To date, no characterization studies have been performed to understand Pythium species diversity in DE. Symptomatic corn seedlings were collected from 33 fields across DE in 2019 and 2020. Isolates were obtained from infected root tissues and identified by molecular sequencing. In total, 14 species were recovered: P. aristosporum, P. arrhenomanes, P. attrantheridium, P. catenulatum, P. dissotocum, P. graminicola, P. inflatum, P. irregulare, P. oligandrum, P. periplocum, P.spinosum, P. sylvaticum, P. tardicrescens, and P. torulosum. The dominant species recovered was P. graminicola, accounting for 66% of the isolates. Five species were screened for fungicide sensitivity to calculate the EC50 of mefenoxam, ethaboxam, and picarbutrazox which are the most commonly used active ingredients to manage species of Pythium in corn seed treatment packages. All species tested were sensitive to mefenoxam and picarbutrazox. For ethaboxam, P. torulosum was the only species with an EC50 value > 10 µg ml 1. Ten species were screened for fungicide sensitivity to mefenoxam, ethaboxam, or picarbutrazox at 18, 21, and 25ºC. As temperatures increased, percent inhibition was reduced in 40, 70, and 80% of the species screened for sensitivity to ethaboxam, picarbutrazox, and mefenoxam, respectively. Nine of these species were screened for isolate aggressiveness in greenhouse panels to examine impact on emergence, shoot height, shoot weight, and root weight. While all species were recovered from inoculated roots, P. arrhenomanes, P. attrantheridium, P. spinosum, and P. sylvaticum had the greatest root weight reduction.

Impact of Green Tea Consumption and Its Extracts on Fat Reduction and Weight Loss

Introduction: Obesity and overweight are major health problems and challenges in the world today. It is the task of modern pharmacology, medicine and dietetics to search for new therapeutic methods to reduce body weight and body fat. Green tea has been a focus of research on its effects on weight reduction for many years. This article will analyse the available studies on the effectiveness of green tea on body weight and body fat reduction in obese and overweight people. Aim of the study: The aim of this review is to analyse the available literature in order to answer the question of whether green tea and green tea extracts (GTE) have an effect on weight loss, body fat reduction and associated metabolic processes.Materials and method: For a comprehensive review on the effects of green tea on weight and body fat reduction, we reviewed studies and literature available in databases such as PubMed and Google Scholar by searching through keywords such as ‘green tea’, ‘obesity’, ‘fat’, ‘weight loss’, ‘matcha’.Conclusion: green tea and its isolated substances such as epigallocatechin-3-O-gallate (EGCG) appear to have a positive effect on weight and body fat reduction in obese and overweight individuals. It is likely that consumption of green tea extract increases fat oxidation during exercise. In addition, supplementation had a positive effect in a group of diabetics, polycystic ovary syndrome and metabolically stressed patients. The best effects from supplementation were obtained by those who additionally had physical activity. It is suggested that research on green tea, especially on matcha, should continue, as very little reliable research has been produced on this topic

Tirzepatide – a new hope for type 2 diabetes mellitus and obesity management. A literature review.

INTRODUCTION AND PURPOSE. While obesity and type 2 diabetes mellitus (T2DM) are defined (according to WHO) as civilization diseases we are still searching for the ideal tool to fight them. Recently, the Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved tirzepatide subcutaneous injections as monotherapy or combination therapy, with diet and physical exercise, to achieve better glycemic blood levels in patients with diabetes and weight reduction among obese and overweighted patients. This review evaluates the efficacy and safety of using tirzepatide based on GIP/GLP-1 agonists clinical trials. MATERAILS AND METHODS. Literature available in the PubMeb Database and Google Scholar Databases was reviewed using keywords. RESULTS AND CONCLUSIONS. Tirzepatide is a novel medicine which stands against type 2 diabetes and obesity pandemic. Combining two agonists of GIP and GLP-1 receptors helps decrease glycemic blood levels, HbA1c levels and reducing body weight in more efficient way than the GLP-1 receptor agonists. All these effects have also resulted in minimizing cardiovascular risk which is observed as an improvement in heart failure, hyperlipidemia and hypertension. Beyond that, the recent data present possible positive long-term effect of tirzepatide in such diseases as MAFLD (metabolic associated fatty liver disease) and OSA (obstructive sleep apnea). However, triagonists, achieving a concurrent activation of GLP-1, GIP, and glucagon receptors, normalize body weight in a manner superior to that of monoagonists and dual agonists. Therefore, the triple agonism or other than GIP/GLP-1 combinations could soon represent a new standard for pharmaceutical interventions. KEYWORDS: tirzepatide; obesity; type 2 diabetes; weight reduction; GIP; GLP-1.

Cardiovascular, Metabolic, and Safety Outcomes with Semaglutide by Baseline Age: Post Hoc Analysis of SUSTAIN6 and PIONEER6.

The high risk of cardiovascular events in people with type2 diabetes increases with age. The cardiovascular effects of once-weekly subcutaneous and once-daily oral semaglutide versus placebo in people with type2 diabetes at high cardiovascular risk were investigated in the SUSTAIN6 and PIONEER6 cardiovascular outcomes trials, respectively. It is unknown whether the effects of semaglutide are age dependent. This post hoc analysis evaluated cardiovascular, metabolic, and safety outcomes with semaglutide versus placebo in age subgroups (≤ 60; > 60 to ≤ 65; > 65 to ≤ 70; and > 70years) pooled from SUSTAIN6 and PIONEER6. Major adverse cardiovascular events (composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke), changes from baseline in glycated hemoglobinA1c (HbA1c) and body weight, and adverse events were analyzed. Semaglutide reduced major adverse cardiovascular events and its components versus placebo across age subgroups (most hazard ratios < 1.0; pinteraction > 0.05). The treatment difference in HbA1c reduction was greater in those aged ≤ 60years than in older subgroups (pinteraction = 0.01). Reductions in body weight with semaglutide versus placebo were consistent across agesubgroups (pinteraction = 0.124). Serious adverse events or severe hypoglycemic episodes did not differ between semaglutide and placebo across age subgroups. Semaglutide consistently reduced major adverse cardiovascular events and body weight versus placebo across age subgroups; its safety profile did not differ with age. These results suggest that relaxing HbA1c targets based solely on age may not always be required for people with type2 diabetes. SUSTAIN6 (NCT01720446) and PIONEER6 (NCT02692716) are registered at ClinicalTrials.gov.

Responses in organs, sperm, steroid hormones and CYP450 enzyme in male mice treated by quinestrol only or in conjunction with clarithromycin

Pest rodents persistently undermine crop yields and food security. Fertility control could be a viable alternative for managing rodent populations. This study investigates the antifertility effects of various concentrations of clarithromycin combined with 1.0 mg/kg quinestrol on male rodents to determine an effective contraceptive dose that minimizes quinestrol usage, addressing key concerns such as potential environmental residue, which may impact ecological balance, and poor palatability, which could reduce ingestion and limit the sterilant’s effectiveness. Male mice were divided into five groups and administered different doses of clarithromycin or clarithromycin and quinestrol for three consecutive days, while the control group received sunflower seed oil only. After seven days, organ weights, reproductive organ weights, sperm density, serum hormone levels, and CYP3A4 content in small intestinal and liver tissues were measured to assess persistent effects. Compared with the control group, all treatment groups had significant reductions in epididymal weight, seminal vesicle weight, and serum T and LH levels. Higher concentrations of clarithromycin (2 mg/kg and 10 mg/kg) significantly impacted reproductive metrics, including sperm density, organ weights, and serum LH and testosterone levels, though complete sterilization was not achieved, with more than 60 million cauda epididymal spermatozoa remaining. However, the combination demonstrated potential as an effective strategy for male fertility control. The combination of 2.0 mg/kg clarithromycin and quinestrol can mitigate organ enlargement seen with quinestrol alone. This combination also decreased total enzyme content, thereby diminishing quinestrol’s induction of CYP3A4, which may increase the sterilization effectiveness of the treatment.

Effects of repetitive transcranial magnetic stimulation therapy on weight and lipid metabolism in patients with treatment-resistant depression: A preliminary single-center retrospective cohort study.

This study aimed to elucidate the effects of repetitive transcranial magnetic stimulation (rTMS) on weight, body mass index (BMI), and lipid metabolism in patients with treatment-resistant depression (TRD). This retrospective observational study included patients with TRD who received rTMS treatment at the Jikei University Hospital from September 2018 to August 2021. The patients were diagnosed based on the DSM-5 and ICD-10 criteria and treated using the NeuroStar TMS System. For 3-6 weeks, 10-Hz rTMS was administered to the left dorsolateral prefrontal cortex at 120% motor threshold. The primary outcomes were changes in weight and BMI, whereas the secondary outcomes included changes in total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol levels, thyroid function indicators, as well as HAMD-17, HAMD-24, and Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Statistical analysis was conducted using paired t-tests and repeated measures ANOVA. Among the 34 patients (20 men and 14 women) included, no significant changes were observed in weight or BMI after rTMS treatment (average weight reduction: -0.50 kg, 95% CI: -0.14 to 0.56, p = 0.24; average BMI reduction: -0.21, 95% CI: -0.10 to 0.61, p = 0.15). However, significant reductions in total, HDL, and LDL cholesterol levels and FT4 were observed. Furthermore, the HAMD-17, HAMD-24, and MADRS scores significantly increased post-treatment. rTMS treatment did not affect weight or BMI in patients with TRD but is believed to improve lipid metabolism.

Efficacy and Safety of GLP-1 Agonists on Metabolic Parameters in Non-diabetic Patients with Inflammatory Bowel Disease.

Obesity in patients with IBD is increasing, accompanied by an increase in metabolic comorbidities. Although GLP-1 agonists have shown promise in weight reduction, their efficacy and safety in patients with IBD are underexplored. This study evaluated the impact of GLP-1-based therapies on weight loss and metabolic parameters in non-diabetic patients with IBD. We conducted a single-center observational cohort study that included adult patients with IBD who were started on GLP-1-based therapy (semaglutide or tirzepatide) for weight loss from January 2021 to April 2024. The primary outcomes were changes in BMI and total body weight. Secondary outcomes included tolerability, safety, and changes in metabolic risk factors. The study included 36 patients with IBD, predominantly female (64%), with a median age of 45.5 years (IQR 41-51.5 years). The majority (67%) had Crohn's disease (CD) and on advanced therapy (86%). BMI significantly decreased from 34.0 (IQR 31.0-38.2) to 31.0 (IQR 29.0-36.1) with GLP-1-based therapy (p < 0.0001). Total body weight (TBW) significantly decreased by a median of 8.15 kg (IQR 15.9-2.2 kg; p < 0.0001). Although a decrease in total cholesterol and glycated hemoglobin was seen, this was not statistically significant (p = 0.0634 for total cholesterol, p = 0.0536 for glycated hemoglobin). No significant changes were observed in ALT or CRP levels. The most common side effects were nausea (31%) and constipation (25%). Semaglutide and tirzepatide can effectively reduce BMI in non-diabetic patients with IBD with manageable side effects. However, further studies are required to explore the long-term safety of GLP-1 agonists in the IBD population.

Sodium-glucose co-transporter 2 inhibitors in left ventricular assist device and heart transplant recipients: a mini-review.

In recent years, sodium-glucose co-transporter 2 inhibitors (SGLT2i) emerged as promising therapeutic agents in managing heart failure (HF). They demonstrated a significant impact on reducing HF hospitalizations and related mortality in patients with reduced and preserved ejection fraction. However, evidence supporting their use in patients with left ventricular assist device (LVAD) and heart transplant (HT) recipients is still limited. We identified six key studies investigating the safety and efficacy of SGLT2i in LVAD and HT recipients. In patients with LVAD, prescription of SGLT2i was predominantly associated with improved fluid management and reduced pulmonary artery pressures. However, the results regarding their effects on body weight, hemoglobin A1c, diuretic use, and right ventricular function were contradictory. In terms of safety, SGLT2i were generally well-tolerated in the LVAD population, and the reported incidence of adverse events was low. In HT recipients, SGLT2i were associated with better glycemic control and weight reduction. No relevant adverse events were reported. Despite these encouraging results, the long-term safety and efficacy of SGLT2i in these vulnerable patient populations are yet to be investigated. Future randomized controlled trials are needed to address existing gaps in evidence and help integrate SGLT2i into clinical practice for LVAD and HT recipients.

Hepatotoxic Medicinal Plants in Weight Loss Formulations Sold at Ver-o-Peso Market, Amazon Region, Brazil.

Obesity represents a significant global public health challenge. Various therapeutic strategies for weight reduction are available, including formulations containing medicinal plants, which are favored due to their availability and low cost. The efficacy and safety of these formulations must be evaluated as they can lead to adverse reactions, including severe hepatic injuries. Despite their widespread usage, particularly among residents of the Amazon, there is a considerable gap in knowledge regarding the species of medicinal plants used in these formulations. This study evaluated the labels of natural weight loss products sold from January to October 2022 at the Ver-o-Peso market in Belém, Brazil. A subsequent review of databases was performed to identify plants listed on the labels that were associated with hepatic injuries. In total, 54 plants were identified in these products, primarily in mixed formulations. None of the labels adhered to current legislative standards. Furthermore, nine of these plants were documented in the literature as having hepatotoxic effects, either through invivo or in vitro studies. The presence of medicinal plants that can cause liver injury on the labels of weight loss compounds is a relevant issue requiring rigorous health surveillance intervention.

Impact of adherence to oral nutritional supplements on nutrition status and muscle strength in patients with gastrointestinal cancer: A prospective observational longitudinal study.

Given the lack of evidence regarding the effects of adherence to oral nutritional supplements (ONS) and the types of formulas used in clinical practice, we aimed to assess the impact of adherence to ONS and the high-protein formula on the nutrition status and muscle strength in patients with gastrointestinal cancer. This study evaluated newly diagnosed outpatients with esophageal, gastric, pancreatic, and colorectal cancer prescribed ONS. Nutrition status was assessed using the Patient-Generated Subjective Global Assessment (PG-SGA), and muscle strength was assessed using handgrip strength (HGS) dynamometry. ONS adherence was calculated as the ratio of self-reported intake to the prescribed amount and categorized as ≥80% or <80%. A total of 54 patients were included. Most patients were ≥60 years of age (63%), were diagnosed with colorectal cancer (63%), were classified as stage III and IV (83%), and exhibited nutrition risk or malnutrition according to PG-SGA (89%). Patients with adherence ≥80% to ONS exhibited less weight loss and HGS reduction compared with patients with adherence <80% (P < 0.05). Although patients consuming a high-protein formula maintained HGS and those on a standard formula experienced a reduction, formula type did not predict HGS change in the multivariate analysis. ONS protein intake, adjusted for adherence, was a predictor of weight change (β: 0.09; 95% CI: 0.02-0.2; P = 0.011). Patients with adherence ≥80% to ONS experienced less reduction in both weight and HGS, whereas those consuming a high-protein formula maintained HGS. Notably, ONS protein intake, adjusted for adherence, was an independent predictor of weight change.

Effect of survodutide, a glucagon and GLP-1 receptor dual agonist, on weight loss: a meta-analysis of randomized controlled trials

BackgroundConsidering the increasing prevalence of obesity/overweight, its treatment or prevention with new interventions can greatly help health and reduce its adverse effects in people. One of these new interventions is investigating the effect of Survodutide as a dual agonist of glucagon and GLP-1 receptors, which seems to be able to influence weight loss processes in different ways. In this study, we investigated the effect of injectable Survodutide on weight loss.MethodsIn order to identify all randomized controlled trials that investigated the effects of Survodutide on factores related to obesity, a systematic search was conducted in the original databases using predefined keywords until August 2024. The pooled weighted mean difference and 95% confidence intervals were computed using the random-effects model.ResultsThe Findings from 18 treatment arms with 1029 participants indicated significant reductions in weight (WMD: -8.33 kg; 95% CI: -10.80, -5.86; I2 = 99.6%), body mass index (BMI) (WMD:-4.03 kg/m2; 95% CI: -4.86, -3.20; I2 = 72.7%), and waist circumferences (WC) (WMD: -6.33 cm; 95% CI: -8.85 to -3.81; I2 = 99.5%) following the Survodutide injection compared to the control group. Subgroup analysis reveals that longer interventions (more than 16 weeks) and higher doses (more than 2 mg/week) of Survodutide are associated with more significant reductions in weight and WC. These results were also observed in the meta-regression analysis.ConclusionsThe results of this meta-analysis show that Survodutide is effective in reducing weight, BMI and waist circumference, especially with longer interventions and higher doses.

Sex-specific dietary habits and their association with weight change in healthy adults

BackgroundDietary intake plays a pivotal role in the prevalence and management of obesity. While women and men exhibit differences in dietary habits and food-related behaviors, sex-based weight loss recommendations are lacking. This study aims to examine the impact of specific foods and food categories on weight reduction in men and women over a two-year period.MethodsA total of 8,548 participants from the 10K cohort, from 2019 to 2023, were included in the analysis (53.1% women, mean age 51.7 years). Anthropometric measurements and laboratory results were collected at baseline and at the two-year follow-up visit. Dietary assessment was based on daily food intake digitally logged through an application for at least 3 consecutive days at both timepoints. We compared intake of macronutrients, micronutrients, food groups and daily energy consumption between sex and body mass index (BMI) categories at baseline and weight change categories at follow-up. Using linear regression, we assessed the associations between food categories or specific foods and BMI at baseline as well as weight change percentage at follow-up.ResultsDietary habits varied by BMI and sex. Women and men living with obesity (BMI > 30 kg/m2) reported a greater intake of animal-based protein and lower intake of plant-based proteins and fats at baseline, as compared to participants with normal weight. In linear regression models predicting two-year weight change, including age, income, and baseline weight, the explained variance was 5.6% for men and 5.8% for women. Adding food categories and specific foods increased the explained variance to 20.6% for men and 17.5% for women. Weight reduction in men was linked to daily consumption of an egg (1.2% decrease) and beef (1.5% decrease), while in women, the most pronounced reductions were associated with an apple (1.2% decrease) and cashew nuts (3.4% decrease). Notably, total energy intake changes significantly impacted weight outcomes only in women.ConclusionsSex-specific dietary habits significantly influence weight change over time. In men, weight loss was primarily associated with the addition of animal-based protein, while in women, it was linked to caloric deficit and plant-based fat, suggesting that sex-based nutritional interventions may demonstrate greater efficacy.Trial registrationNCT05817734 (retrospectively registered January 31, 2023).

Elephantiasis and its cure: case report

Introduction: Lymphedema is a clinical condition stemming from a lymphatic system failure. The insufficiency of the lymphatic system can causes the abnormal accumulation of protein-rich fluid in the interstitial, which triggers a adverse consequence such a and fibrosis. This study describes a case of a patient who has been cured of elephantiasis for ten years but continues to have lymphedema. Description case: Patient information: A 78-year-old woman had a history of bilateral lower limb lymphedema, clinical diagnosis that had been worsening throughout her life bilateral despite undergoing treatment and had progressed to stage III (elephantiasis). Clinical findings: The patient was sent to the Clínica Godoy-Sao Jose do Rio Preto-Brazil ten years ago and reported having undergone several forms of treatment, but without impeding the progression of the condition. Therapeutic intervention: The patient was submitted to intensive treatment for three weeks, during which time a 21-kilogram reduction in weight and a 66-cm reduction in circumference occurred. After three weeks, the patient began undergoing treatment at home with laced compression stockings. At the follow-up evaluation, electrical bioimpedance analysis, perimeter measurements and volumetry were performed, which revealed the reduction in lymphedema to standards of normality. The patient has completed 10 years of treatment and has maintained the results using compression stockings. Conclusion: Elephantiasis is curable, but lymphedema is not. Like any other chronic disease, constant treatment is needed to maintain the results.

Preparation and characterization of Tobacco polysaccharides and its modulation on hyperlipidemia in high-fat-diet-induced mice.

This study aimed to investigate the structural properties of tobacco polysaccharide (TP) and its mechanism of modulating hyperlipidemia in high-fat diet-induced mice. The structural properties of TP were characterized by FT-IR, 1HNMR, SEM, AFM and thermogravimetric analysis. And the regulatory mechanism of TP on lipid metabolism was investigated in hyperlipidemia mice. These results showed that TP had a high composition of reducing monosaccharide and the glycosidic bond type was α-glycosidic bond. The intervention by TP resulted in a significant reduction of body weight and improvement in lipid accumulation. And the modulation mechanism by which TP ameliorated the abnormalities of lipid metabolism was associated with the expression levels of lipid metabolism-related genes and serum exosomes miRNA-128-3p, as well as the modulation of structure and abundance of the gut microbiota in mice. In addition, TP treatment significantly increased the content of short-chain fatty acids (SCFAs) in mice feces. The results of molecular docking and dual-luciferase assay exhibited a good interaction between propionic acid and PPAR-α, and it was hypothesized that the interaction might further ameliorate the hyperlipidemia. Therefore, TP can regulate the expression levels of lipid metabolism-related genes through miRNAs from serum exosomes and SCFAs from gut microbiota.

Real-World Comparison of Oral Versus Injectable Semaglutide for the Reduction of Hemoglobin A1C and Weight in Patients with Type 2 Diabetes.

No head-to-head comparisons of semaglutide formulations currently exist in the literature. In practice, many may think that oral and injectable semaglutide formulations are interchangeable, although there is currently limited real-world data to determine whether this is accurate. The purpose of this study was to determine the effect of oral versus injectable semaglutide on hemoglobin A1C (HbA1C) and weight in patients with type 2 diabetes (T2D). This was a retrospective single-center review of adult patients who had a diagnosis of T2D and were treated with oral or injectable semaglutide between November 1, 2019, and July 31, 2022. Primary outcome was a comparison of changes in HbA1C (%) and weight (kg) from baseline to 6 months between patients receiving oral versus injectable semaglutide, stratified according to highest dose received. Secondary outcomes included frequency of dose reductions and discontinuations, achievement of clinical goals, and presence of an embedded clinical pharmacist at patients' primary care office. A total of 105 patients were included. Patients experienced mean decreases in HbA1C and weight from baseline to 6 months of -1.75% (P < 0.001) and -3.64 kg (P = 0.015), respectively, in the oral semaglutide group and -1.35% (P < 0.001) and -5.26 kg (P < 0.001), respectively, in the injectable semaglutide group. When directly comparing semaglutide formulations, oral semaglutide demonstrated a 0.4% greater numerical reduction in HbA1C (P = 0.523) and injectable semaglutide demonstrated a 1.62-kg greater numerical reduction in weight (P = 0.312). Adverse events (AEs) occurred more frequently with oral semaglutide than with injectable semaglutide (16.7% vs 4.9%). Discontinuation due to AEs was more common with oral semaglutide. In this study, patients with T2D who received oral semaglutide demonstrated greater reductions in HbA1C, whereas those treated with injectable semaglutide had greater reductions in weight, although there were no statistically significant reductions in HbA1C or weight between the 2 formulations. Rates of AEs and discontinuation were more common in the oral semaglutide group.

Association between weight reduction achieved with tirzepatide and quality of life in adults with obesity: Results from the SURMOUNT-1 study.

The SURMOUNT-1 trial investigated effects of tirzepatide, a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, on body weight in participants with obesity or overweight. This analysis evaluated changes in patient-reported outcomes (PROs) assessing physical function, psychosocial well-being, and overall health aspects of participants' health-related quality of life (HRQoL) in SURMOUNT-1. PRO instruments included the Impact of Weight on Quality of Life-Lite Clinical Trials version (IWQOL-Lite-CT), Short Form Survey-36 version 2 (SF-36v2) and EQ-5D-5L. Scores were analysed by treatment group and by categorical degree of weight reduction group: >0 to <5%, ≥5 to <10%, ≥10 to <20% and ≥20%. Relevant PROs were evaluated for participants with or without physical or psychosocial limitations at baseline, as measured by Patient Global Impression of Status for physical activity (PGIS) and Patient Health Questionnaire-2 (PHQ-2), respectively. All tirzepatide groups demonstrated significant improvements in PRO scores versus placebo. There was a consistent trend of incremental PRO improvement with greater degrees of weight reduction, starting from ≥5% weight reduction. Participants achieving ≥20% weight reduction demonstrated the greatest changes from baseline to week 72 (SF-36v2 Physical Component Summary, 4.60; SF-36v2 Mental Component Summary, 0.80; IWQOL-Lite CT Total score, 24.7). Those with baseline physical and psychosocial limitations experienced greater improvements than those without. Tirzepatide treatment was associated with improved HRQoL compared to placebo in people with overweight or obesity. Higher percentages of weight reduction were associated with greater improvements. Clinical trial registration number for SURMOUNT-1: NCT04184622.

Effect of FTO Gene polymorphism on anthropometric, hemodynamic, and autonomic variables in adolescents

Objective: The study aimed to analyze the influence of physical activity levels and the rs9939609 polymorphism (FTO gene) on anthropometric, hemodynamic, and cardiac autonomic variables in public school students. Methods: A total of 288 students (aged 11 to 18, both sexes) from public schools in São Luís, Maranhão, were divided into four groups: sedentary AA+AT (AA+AT sed), active AA+AT (AA+AT activ), sedentary TT (TT sed), and active TT (TT activ). Evaluations included the International Physical Activity Questionnaire, weight, height, body mass index (BMI), buccal cells collection for DNA extraction, systolic (SBP) and diastolic (DBP) blood pressure measurements, and heart rate variability (HRV) analysis. A chi-square test for allelic associations was applied a 5% significance level. Results: No significant differences were observed in DBP or heart rate (HR). The active groups (AA+AT activ and TT activ) exhibited reductions in weight and METs/min/week compared to their respective sedentary groups (P&lt;0.05). The TT activ group also demonstrated reductions in SBP and BMI compared to the TT sed group (P&lt;0.05). The TT activ group had higher HRV in the RR time domain (ms) compared to the TT sed group (P&lt;0.05), though no significant differences were found in other HRV variables. Conclusions: The FTO gene polymorphism influences cardiac autonomic modulation, while physical activity levels affect anthropometric variables.

Optimization and Structural Analysis of Automotive Battery Packs Using ANSYS

The development of new energy vehicles, particularly electric vehicles, is robust, with the power battery pack being a core component of the battery system, playing a vital role in the vehicle’s range and safety. This study takes the battery pack of an electric vehicle as a subject, employing advanced three-dimensional modeling technology to conduct static and dynamic analyses. Through weight reduction and structural optimization, an innovative power battery pack design scheme is proposed, aiming to achieve a more efficient and lighter electric vehicle power system. The main research tasks are as follows: Firstly, we designed the main load-bearing components of a certain electric vehicle’s power battery pack and established a three-dimensional (3D) model. Then, the model was simplified according to the actual stress conditions of the power battery pack of the electric vehicle and imported into finite element analysis (FEA) software. Next, based on the fundamental principles of the finite element method (FEM), we conducted static analyses under three conditions: bumpy road sharp left turn, bumpy road sharp right turn, and bumpy road emergency braking. The analysis results indicate that the strength of the battery pack meets the allowable requirements, suggesting that the lower housing design has significant redundancy, providing guidance for subsequent optimization. Finally, through modal analysis, we extracted the first six modes of the power battery box, with the first mode frequency being 33.69 Hz. This suggests that the battery pack may experience resonance during actual operation. Based on the static and modal analysis results, we proposed a structural optimization and lightweight design solution for a certain electric vehicle battery pack and compared it with the pre-optimization data.

Non-clinical and first-in-human characterization of ECC5004/AZD5004, a novel once-daily, oral small-molecule GLP-1 receptor agonist.

GLP-1 receptor agonists (GLP-1 RAs) are proven therapies for type 2 diabetes mellitus (T2DM) and overweight or obesity. We performed non-clinical and first-in-human (FIH) evaluation of ECC5004/AZD5004, an oral small-molecule GLP-1 RA. ECC5004 was profiled in cell lines overexpressing human GLP-1R, in glucose-stimulated insulin secretion (GSIS) assays in a human β-cell line and non-human primates (NHPs). To evaluate safety, ECC5004 was orally administered to NHPs for 9 months and a phase I, double-blind, placebo-controlled FIH study was conducted. This study evaluated single doses of ECC5004 (1-300 mg) in healthy volunteers, and multiple daily doses (5, 10, 30 and 50 mg) in patients with T2DM for 28 days. ECC5004 bound to the hGLP-1R (IC50 = 2.4 nM) augmented cAMP signalling without β-arrestin-2 recruitment or receptor internalization. ECC5004 potentiated GSIS in both EndoC-βH5 cells (EC50 = 5.9 nM) and in vivo in NHPs (EC50 = 0.022 nM). Dose-dependent body weight changes compared to control were seen in the 9-month NHP toxicity study. In the first-in-human study, ECC5004 was well tolerated with no serious adverse events. Dose-dependent reductions in glucose and body weight were observed with a dose-proportional exposure at doses ≥25 mg. ECC5004 engaged the GLP-1R across the therapeutic dose range tested and had a safety and tolerability profile consistent with other GLP-1 RAs, along with a pharmacokinetic profile compatible with once-daily oral dosing. These data support continued development of ECC5004 as a potential therapy for T2DM and overweight or obesity. NCT05654831.