Anti-obesity Research Articles

Curcumol effectively improves obesity through GDF15 induction via activation of endoplasmic reticulum stress response

The escalating prevalence of obesity presents a formidable global health challenge, underscoring the imperative for efficacious pharmacotherapeutic interventions. However, current anti-obesity medications often exhibit limited efficacy and adverse effects, necessitating the exploration of alternative therapeutic approaches. Growth differentiation factor 15 (GDF15) has emerged as a promising target for obesity management, given its crucial role in appetite control and metabolic regulation. In this study, we aimed to investigate the efficacy of curcumol, a sesquiterpene compound derived from plants of the Zingiberaceae family, in obesity treatment. Our findings demonstrate that curcumol effectively induces the expression of GDF15 through the activation of the endoplasmic reticulum stress pathway. To confirm the role of GDF15 as a critical target for curcumol’s function, we compared the effects of curcumol in wild-type mice and Gdf15-knockout mice. Using a high-fat diet-induced obese murine model, we observed that curcumol led to reduced appetite and altered dietary preferences mediated by GDF15. Furthermore, chronic curcumol intervention resulted in promising anti-obesity effects. Additionally, curcumol administration improved glucose tolerance and lipid metabolism in the obese mice. These findings highlight the potential of curcumol as a GDF15 inducer and suggest innovative strategies for managing obesity and its associated metabolic disorders. In conclusion, our study provides evidence for the efficacy of curcumol in obesity treatment by inducing GDF15 expression. The identified effects of curcumol on appetite regulation, dietary preferences, glucose tolerance, and lipid metabolism emphasize its potential as a therapeutic agent for combating obesity and related metabolic disorders.

Abstract 4135712: Mortality and Cardiovascular Complications Associated with Weight Loss Drugs among Breast Cancer Females Under Cardiotoxic Therapies: A Real-World Populational Study in the United States

Background: Obesity is an adverse prognostic factor for breast cancer (BC). While liraglutide and semaglutide, derived from antidiabetic glucagon-like peptide-1 receptor agonists (GLP1RA), are established weight loss drugs known for their cardiovascular safety in the general obese population, their safety in BC patients undergoing cardiotoxic antineoplastic therapies remains less understood. Objective: To investigate the mortality and cardiovascular outcomes related to GLP1RA used for weight loss among the highly susceptible BC females. Methods: This retrospective cohort study was based on the TrinetX network, comprising real-time health records from over 60 US healthcare organizations. The study population included obese females (≥18 years old) who received at least three prescriptions of either exclusive GLP1RA (liraglutide or semaglutide) or non-GLP1RA weight loss drugs (phentermine, bupropion-naltrexone, orlistat) upon BC diagnosis between 01/01/2015 and 01/01/2022. The index date was the initiation of systemic anti-cancer treatment, including chemotherapy (anthracycline, taxane, or cyclophosphamide), and/or anti-HER2 agents (trastuzumab, pertuzumab, or lapatinib). We used 1:1 propensity score-matching (PSM) to balance demographics, BMI, comorbidities, concurrent medications for cardiovascular diseases and metabolic disorders, BC receptor status and prior treatment, and levels of serum cholesterol (LDL, HDL) and hemoglobin A1c. Cox regression models were applied to compute hazard ratios (HR) and 95% confidence intervals (CIs). Follow-up continued until 05/24/2024, or until adverse cardiovascular events or death occurred. Results: Among 380 PSM-balanced pairs, the GLP1RA group (mean age: 57.6±11) showed significantly lower risks of all-cause mortality (HR 0.593, 95% CI 0.457-0.77), acute heart failure (HR 0.496, 95% CI 0.286-0.859), angina pectoris (HR 0.566, 95% CI 0.343-0.936), and acute stroke (HR 0.661, 95% CI 0.46-0.951) than the non-GLP1RA group (mean age: 57.5±12). Otherwise, no significant difference was shown in acute myocardial infarction (HR 0.787, 95% CI 0.495-1.251), pulmonary hypertension (HR 0.777, 95% CI 0.55-1.099), or arrhythmias (HR 0.829, 95% CI 0.566-1.215). Conclusion: Compared to non-GLP1RA weight loss agents, GLP1RA offers better survival and cardiovascular protection for BC patients undergoing cardiotoxic therapies. Future studies are warranted to validate the safety of these weight loss drugs during the BC treatment continuum.

Abstract 4140191: ChREBP Drives Brown Adipocyte Differentiation and Lipid Utilization for Excess Energy Expenditure

Introduction: Although several anti-obesity drugs have become recently available, they reduce patients’ appetite, which might worsen cardiovascular disease (CVD) prognosis by malnutrition/cachexia. Brown adipose tissue (BAT) oxidizes glucose and lipids for thermogenesis, a process that requires excess energy expenditure provided by uncoupling protein 1 (UCP1) + cells. Recently, critical roles of BAT in cardio-protection have been discovered. Taken together, boosting BAT activity can be a novel anti-obesity treatment suitable for CVD patients. In this study, we aimed to establish anti-obesity strategy by manipulation of the glucose-sensing lipid-storage transcription factor, ChREBP, with unexpected function of boosting lipid utilization in BAT. Methods and Results: Through mouse/human single-cell/nucleus RNA sequencing analyses, we identified ChREBP as specifically expressed in highly thermogenic UCP1 + brown adipocytes ( Fig.A ). To investigate the role of ChREBP in BAT formation, we generated human brown adipocyte-like model from induced pluripotent stem cells (iPSC-BAT, Fig.B ). The iPSC-BAT exhibited high UCP1 and ChREBP expression, multi-locular lipid droplets, and vigorous oxygen consumption. Knocking down ChREBP strongly blocked iPSC-BAT differentiation ( Fig.C ) and impaired lipid utilization ( Fig.D ). Consistently, in vitro deletion of ChREBP in mouse BAT progenitors impeded differentiation, lipid droplet accumulation, and oxygen consumption ( Fig.E-F ). In vivo, BAT-specific deletion of all ChREBP isoforms reduced lipid accumulation and BAT characteristics. Conversely, using a new mouse model for Cre-mediated ChREBPβ overexpression, we showed that ChREBPβ overexpression in BAT (Chβ BATOX) increased BAT cellularity and activated lipogenic machineries, with paradoxical decreased lipid content, suggesting excessively activated lipid consumption in BAT ( Fig.G ). More importantly, Chβ BATOX maintained UCP1 expression and reduced fat volume ( Fig.H ) even after strongly inhibiting BAT activity. Conclusion: In summary, ChREBP is essential for BAT development and thermogenic capacity by affecting lipid utilization. Our results suggest that ChREBPβ activation may be a novel anti-obesity avenue for CVD patients.

Impact of baseline dietary quality on the efficacy of a dietitian-guided weight reduction program.

This pre-post intervention study aimed to assess the relationship between baseline dietary quality and the efficacy of a dietitian-guided weight reduction program, which has not been thoroughly documented to date. Ninety-two consecutive obese or overweight patients visiting a tertiary center clinic for weight reduction were enrolled in this study. Participants received a dietitian-guided weight reduction education program aimed at reducing daily caloric intake by 500kcal and improving adherence to the Mediterranean diet for 3 months. Baseline dietary quality was assessed using the 14-item Taiwanese Mediterranean Diet Adherence Screener (T-MEDAS), where a higher T-MEDAS score reflects greater adherence to the Mediterranean diet. Additional covariates, including dietary behaviors, lifestyle factors, and comorbidities were also recorded. The primary outcome was the percentage of weight reduction at 3 months, analyzed using restricted cubic spline models and generalized estimating equations (GEE) to account for the correlation between weight change and the baseline T-MEDAS scores. Thirty-nine participants were excluded due to major illnesses, use of anti-obesity medications, or loss to follow-up. Among the remaining 53 participants (mean age 41.2 ± 12.8 years, 56.6% female), the average weight reduction was 3.9 ± 3.3% from a baseline weight of 98.5 ± 12.8kg. Participants who did not achieve a weight reduction of more than 5% had higher baseline T-MEDAS scores compared to those who did (5.4 ± 1.7 vs. 4.1 ± 1.8, p = 0.026). A restricted cubic spline model, adjusted for covariates including age, gender, diabetes mellitus (DM), dyslipidemia, and smoking, revealed a significant inverse relationship between higher baseline T-MEDAS scores and weight loss. After controlling for various confounders, GEE analysis demonstrated that higher baseline T-MEDAS scores were significantly associated with less weight loss (beta: -4.1, 95% CI: -5.6 to -2.6, p < 0.001). Higher baseline dietary quality was associated with reduced effectiveness of a dietitian-guided weight reduction program. This suggests that additional strategies may be required to improve the success of weight loss interventions in individuals with higher baseline dietary quality.

Weight loss and metabolic effects of an ALDH1A1-specific inhibitor, FSI-TN42, in a diet induced mouse model of obesity.

Retinoic acid (RA) participates in weight regulation and energy metabolism. Mice lacking ALDH1A1, one of the major enzymes responsible for RA biosynthesis, are resistant to diet-induced obesity. Previously, we identified FSI-TN42 (N42) as an ALDH1A1-specific inhibitor and reported its pharmacokinetics and pharmacodynamics as well as its efficacy in weight suppression. In the first study, C57BL/6 J male mice were fed a high fat diet for 8 weeks to induce obesity. Mice were then divided into three groups and fed (1) moderate fat diet (MFD), (2) MFD + WIN 18,446 (1 g/kg diet), or (3) MFD + N42 (1 g/kg diet) for 8 weeks. A control group of mice were fed a low-fat diet for the entire period. Mice were weighed weekly and fasting glucose was determined every 4 weeks. Tissues were examined for potential toxicity using histopathology and complete blood counts. In the second study, we examined influences of N42 on energy balance and/or appetite by determining food intake, activity and energy expenditure in mice with obesity treated with MFD or MFD + N42. Lastly, we tested fertility with a mating study. N42 significantly accelerated weight loss compared to MFD alone in mice with obesity by reducing fat mass without decreasing lean mass. N42 did not alter food intake or activity levels. While mice treated with N42 lost significantly more weight, they maintained a similar level of energy expenditure compared to mice fed MFD only. Mice fed N42 preferentially used fat postprandially, especially under thermoneutral or mild cold challenge. N42 did not affect male fertility. N42 promotes weight loss when used with MFD in mice with diet-induced obesity without causing significant organ toxicity or male infertility. Future studies will determine if N42 can be used to promote further weight loss if combined with current weight loss drugs.

Efficacy of Anti-obesity Medication (AOM) and Endoscopic Gastric Remodeling (EGR): Analysis of Combination Therapy with Optimal Timing and Agents

Introduction: Endoscopic gastric remodeling (EGR) and anti-obesity medications (AOMs) are effective weight loss therapies. While the efficacy of EGR and AOMs has been established, the effect of combination therapy and its optimal approach remain unknown. Methods: This was a single-center retrospective review of prospectively collected data of patients who underwent EGR. Patients were categorized as: 1) monotherapy – EGR alone, 2) combination therapy – an AOM prescribed within 6 months of EGR and 3) sequential therapy – an AOM prescribed greater than 6 months of EGR. Outcomes included percent total weight loss (%TWL) at 12 months, response rate (≥10%TWL at 12 months) and serious adverse event rate. Results: 208 patients were included. Of these, 65 (34%), 61 (31%) and 82 (35%) underwent monotherapy, combination therapy and sequential therapy, respectively. At 12 months, EGR+GLP-1RA combination therapy achieved the greatest weight loss (23.7±4.6% TWL), while those who began with AOM followed by EGR greater than 6 months later had the lowest weight loss (12.0±7.7%TWL) compared to monotherapy (17.3±10.0% TWL) (p=0.04 and 0.03, respectively). The response rate was 100% for EGR+GLP-1RA combination therapy and 56% for AOM followed by EGR sequential therapy (p=0.02). Conclusion: Combining AOM with EGR appears to result in greater weight loss compared to other strategies, with GLP-1RA as the preferred agent and optimal initiation of both therapies occurring within six months of each other. Prolonged medication use prior to EGR appears to be associated with suboptimal weight loss, suggesting the importance of early referral for adjunctive therapy.

Costs of treating serious adverse effects of drugs used for treatment of obesity: comparison of selected European countries

Drugs for the treatment of obesity show significant effectiveness, but the adverse effects (ADRs) of these drugs are numerous and varied, and some of them are highly cost-generating. Our research aimed to define the health care utilization pattern in treating ADRs of antiobesity therapy, to compare the costs of treating these ADRs among selected European countries, and to identify the key cost drivers. A comparative analysis of the costs of treating the ADRs of antiobesity drugs in 10 European countries (seven EU members and three from the Western Balkans) was conducted, and the impact of parameters of global health expenditures on them was assessed. There are considerable differences in costs of treating adverse antiobesity drug reactions among European countries: costs of treating gastroesophageal reflux disease varied almost 20 times between North Macedonia (12.6 EUR) and Estonia (202.9 EUR). The Gross Domestic Product per capita was an important cost driver in treating the majority of the ADRs studied (p < .001), except for retinopathy, anaphylaxis, and respiratory disorders. The Domestic Private Health Expenditure increased the costs of treating depression (p = .012), upper respiratory tract infection (p = .008), melanocytic naevus (p = .027), and drug-induced hepatitis (p = .023). Investment in pharmaceuticals, medical goods, and preventive care tended to reduce the costs of treating several ADRs, which are seemingly unrelated to the body site or mechanism. Healthcare utilization and costs of treating ADRs to antiobesity drugs vary significantly among European countries. These differences should be considered when creating inputs for cost-effectiveness and budget impact models to decrease their uncertainty.

Why are we still in need for novel anti-obesity medications?

Why are we still in need for novel anti-obesity medications?

Incretin-Based Therapies and Lifestyle Interventions: The Evolving Role of Registered Dietitian Nutritionists in Obesity Care

The emergence of incretin-based therapies, specifically glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and glucose-dependent insulinotropic polypeptide (GIP), as a new class of obesity medications, is dramatically changing obesity care. Use of these medications, known categorically as anti-obesity medications, as part of comprehensive obesity management is associated with significantly greater weight loss and health benefits than found with earlier generation obesity medications. The outcomes reported from medication trials were often achieved in conjunction with lifestyle counseling sessions by a registered dietitian nutritionist (RDN) or other qualified health care professional. Research demonstrates that evidence-based obesity care should incorporate lifestyle interventions. Counseling by a RDN, paired with incretin-based therapies, can play a critical role in supporting adherence to the medication regimen, preventing and managing side effects, adequate nutrient intake, and establishment of lifestyle behaviors for long-term weight and health management. To date, minimal research has been reported on the impact of incretin-based therapies on food and nutrient intake. Until that research is conducted, RDNs and other health professionals can apply knowledge and experience from clients who have undergone other intensive treatments. This article provides considerations for lifestyle interventions, with a focus on medical nutrition therapy (MNT) provided by RDNs, for adults prescribed incretin-based therapies. RDNs have the education and training to provide MNT for people with overweight or obesity, as well as lifestyle counseling on physical activity, stress management, sleep hygiene, goal setting, and other behaviors associated with positive health outcomes. RDNs have a critical role in the integration of incretin-based therapies into obesity management.

Self-awareness Regarding Obesity and Specific Therapy in Patients with Overweight or Obesity and Cardiovascular Diseases from Moscow Region

Objective: Despite the proven effectiveness of lifestyle interventions and specific medications in the treatment of obesity, little is known about their use in real-world practice. . Aims: To study the awareness of patients about the problem of overweight/obesity, as well as the clinical practice of non-drug and drug therapy according to the survey Material and Methods: Eligible patients were recruited from the prospective outpatient registry of patients with cardiovascular diseases. The design of the study was a cross-sectional cohort singlecentre. All of the included patients completed a specifically designed questionnaire. The study included 295 patients (mean age 66.8 ± 11.8 years) with a body mass index (BMI) of ≥ 25 kg/m2. One hundred eight (36.6%) individuals were overweight, 124 (42.2%) had first-class obesity, 42 (14.2%) had second-class obesity, and 21 (7.1%) patients had third-class obesity. Results: 252 patients (85.4%) were informed of being overweight/obese, and all of them received non-drug recommendations for the treatment of obesity. Anti-obesity medications (AOM) were recommended only to 25 (8.5%) patients: 3 – overweight, 11 – obesity class I, 6 obesity class II, and 5 – obesity class III. Twenty-one (7.1%) patients took the prescribed medications (84% adherence). The drugs were more often taken by patients with class II and III disease (40.5% and 57.1% of patients, respectively). Overweight (8.5%) and class I obesity (18.0%) patients took these drugs less often (p &lt; 0.0001). Conclusion: The results of the survey have demonstrated good awareness of patients about their obesity/overweight and quite frequent use of non-drug obesity therapy. However, the rate of AOM prescription was extremely low.

Transforming the diabetes outcomes for people with mental illness

AbstractThere is a complex bidirectional relationship between diabetes and mental illness, where diabetes is associated with an increased prevalence of a range of mental disorders and several mental illnesses increase the risk of diabetes. The reasons why people with mental illness are at higher risk of diabetes and vice versa are multifactorial. When diabetes and mental illness occur together, the outcomes for both conditions are worsened, and the co‐morbidity places a higher burden on the individual living with the conditions.Severe mental illness is associated with a twofold increased risk of diabetes, and the onset of diabetes is approximately 10 years earlier in people with mental illness than in the general population. Health behaviour interventions to reduce the incidence of diabetes may be less effective than previously thought. However, trials on obesity drugs, particularly glucagon‐like peptide‐1 receptor agonists, are showing promise. Diabetes care for people with severe mental illness seems to have improved in the past decade. Interventions have been developed to address the unique challenges of living with severe mental illness and diabetes.Depression is twice as common in people with diabetes. Depression increases the risk of diabetes and vice versa. Although general population risk factors for depression apply to people with diabetes, diabetes‐specific risk factors include the development of complications and insulin use in people with type 2 diabetes. Managing depression includes efforts to prevent depression, timely diagnosis and treatment with psychological or pharmacological treatments.Health care professionals have a responsibility to ensure that people with mental illness and diabetes are not disadvantaged.

Effective but inaccessible antiobesity medications: A call for sharing responsibility for improving access to evidence-based care.

Effective but inaccessible antiobesity medications: A call for sharing responsibility for improving access to evidence-based care.

Efficacy and Safety of Novel Twincretin Tirzepatide, a Dual GIP/GLP-1 Receptor Agonist, as an Anti-obesity Medicine in Individuals Without Diabetes: A Systematic Review and Meta-analysis.

Aims: To date, no meta-analysis has analyzed the efficacy and safety of tirzepatide as an anti-obesity medication in individuals without diabetes. This meta-analysis was undertaken to address this knowledge gap. Materials and methods: Electronic databases were searched for randomized controlled trials (RCTs) involving individuals with obesity without diabetes receiving tirzepatide in the intervention arm and placebo in the control arm. The primary outcome was the percentage change in weight from baseline, and the secondary outcomes included the change in weight from baseline; a weight reduction of ≥5%, ≥10%, ≥15%, ≥20% and ≥25%; glycaemic parameters; lipid parameters and adverse events. Results: From 281 initially screened articles, data from 2 RCTs involving 1,852 participants were analyzed. The efficacy and safety of tirzepatide 15 mg (or the highest tolerable dose) versus placebo were analyzed. The percentage change in body weight was higher with tirzepatide than with placebo (mean difference [MD]: -19.44%; 95% confidence interval [CI]: -22.48 to -16.41; p<0.00001). Tirzepatide also had a higher absolute reduction in body weight (MD: -17.55 kg; 95% CI: -32.15 to -2.95; p<0.00001). Higher percentages of people on tirzepatide had a weight reduction of ≥5%, ≥10%, ≥15%, ≥20% and ≥25% compared with placebo. Improvements in glycaemic and cardiometabolic parameters were observed with tirzepatide. Tirzepatide was associated with a higher number of participants with one or more adverse events, which leads to treatment discontinuation, and severe or serious gastrointestinal events. Conclusion: This meta-analysis provides exciting data on the impressive weight loss properties of tirzepatide over 72 weeks of clinical use in individuals with obesity without diabetes.

Twelve-month analysis of real-world evidence from a telehealth obesity-treatment provider using antiobesity medications.

The objective of this study was to describe weight changes in members of a large-scale telehealth obesity-treatment provider who were using antiobesity medications (AOMs). This retrospective observational study analyzed real-world data from adults who initiated AOM treatment with the WW International, Inc. (formerly Weight Watchers) Clinic telehealth program between January 2022 and July 2023 (n = 53,590). The main outcomes were changes in body weight over 12 months, side effects over follow-up, and medication usage patterns. The 53,590 patients who initiated treatment were predominantly female (88.6%), with a mean BMI of 36.9 kg/m2. Mean (SD) treatment duration was 5.3 (4.3) months. Program retention rates based on the number of patients whose time from enrollment was at least 3, 6, 9, and 12 months were 78% (n = 39,907/51,247), 63% (n = 25,515/40,203), 58% (n = 15,472/26,794), and 77% (n = 6459/8394), respectively. Average weight loss was 8.9% at 3 months (n = 37,565), 14.1% at 6 months (n = 24,140), 17.7% at 9 months (n = 15,169), and 19.4% at 12 months (n = 6089). Glucagon-like peptide-1 receptor agonist (GLP-1-RA)-based treatments were predominant. Side effects were consistent with the classes of medications used, and frequency declined over time. This real-world analysis of a telehealth-delivered obesity-treatment program demonstrated outcomes consistent with recent phase 3 clinical trials of AOMs, suggesting generalizability beyond clinical trial and in-person settings.

The Phytochemistry and Medicinal value of Psidium guajava ( guava ) : Antiobesity Effect

Obesity in society has reached epidemic proportions in the 21 st century. Being Overweight is not only appearance issue but also is actually a medical concern, because it is serious health condition. Diabetes and Heart diseases that can stem from obesity . The plant Psidium guajava Linn (Guava) is used not only as food but also as folk medicine. We subjected the leaves of these plant for Alcoholic extraction using solvent Ethanol and extract were prepared we infer that the oral administration of guava leaves extract shows Anti Obesity effect (weight loss). So this study proves that the guava leaves extract helps to control obesity.

Anti-obesity treatment preferences of healthcare providers and people living with obesity: A survey-based study.

A cross-sectional, online survey was conducted in the United Kingdom, France, Germany, and the United States (14 November-22 December 2022) to investigate preferences for anti-obesity medication (AOM) among people with obesity (PwO) and healthcare providers (HCPs). Eligibility: Adult PwO who self-defined their body type as overweight/obese, were trying to lose weight and had BMI ≥30.0 or 27.0-29.9 kg/m2 with ≥1 obesity-related complication; HCPs had to see ≥30 PwO in a typical month and be a decision-maker regarding their weight loss. The survey included 2500 PwO and 500 HCPs. Exercise (96%) and diet (90%) were the most common weight management methods; AOM use was low (8%). Key barriers to use of prescribed AOMs among PwO were not wanting to take AOM (34%), side effects concerns (33%), and not trusting AOM (26%). Most HCPs (79%) had prescribed/recommended AOMs. Efficacy was the most common reason for preferring one of the shown product profiles among PwO (60%) and HCPs (86%); improving cardiovascular risk was also important to 95% of HCPs when deciding which AOM to prescribe. AOM preference is largely driven by efficacy. Increasing knowledge could help to address barriers to AOM use and improve outcomes for PwO.

Cardiometabolic outcomes in patients with overweight and obesity undergoing weight loss trials : a network meta-analysis

Abstract Objective Cardiometabolic outcomes are intrinsically linked with obesity. According to a study by Jayedi A et al. a 5kg weight gain could increase CVD mortality and MI risk by 11% and 18% respectively, with most overweight and obese patient also suffering from cardiometabolic derangements. This network meta-analysis evaluates cardiometabolic effects bought about by glucagon-like peptide 1 receptor agonists (GLP-1 RA) and other weight loss drugs in an overweight and obese population. Methods Cochrane CENTRAL, Embase and Medline were searched for randomised clinical trials (RCTs) on GLP-1 RA and United States Food and Drug administration weight loss drugs. A network meta-analysis was performed, using risk ratios(RR) to compare the efficacy of the interventions against one another. Network diagrams and surface under the cumulative ranking curve analysis were generated for the following cardiometabolic outcomes ( LDL, HDL, TC, TG, HbA1c, FPG, SBP and DBP). Results Among the cardiometabolic outcomes analysed, the GLP-1RA’s consistently ranked on top, with tirzepatide followed by semaglutide and then liraglutide. In terms of glycaemic control, tirzepatide 15, 10 and 5mg ranked first in a dose dependent manner(SUCRA = 0.8480, 0.8410, 0.6725) followed by semaglutide1.7mg(SUCRA= 0.6232). Tirzepatide 15mg did not achieve statistical significance compared to semaglutide 1.0mg (MD: -0.77, 95%CI: -2.04 to 0.50) or liraglutide1.8mg (MD: -0.64, 95%CI: -1.68 to 0.41). In reducing blood pressure, tirzepatide exhibiting a dose dependent reduction with Tirzepatide 15mg, (SUCRA =0.9457),10mg(SUCRA=0.9069)and 5mg(SUCRA=0.8419) followed by semaglutide 1.7mg (SUCRA =0.7415) then liraglutide 1.8mg(SUCRA = 0.5521).Tirzepatide 15mg demonstrated statistical significance compared to semaglutide 1.0mg (MD: -3.53, 95%CI: -6.78 to -0.27) and liraglutide 3.0mg (MD: -3.47, 95%CI: -5.59 to -1.36). The GLP-1RA’s also exhibited superiority in lipid reduction for TC and TG, with tirzepatide reducing TC (SUCRA = 0.7867) and TG(SUCRA = 0.9843) followed by semaglutide 1.7 mg (SUCRA = 0.7796) for TC and tirzepatide 10 mg (SUCRA = 0.9018) for TG. Orlistat 120mg(SUCRA =0.8789) and 60mg(SUCRA= 0.8458) were superior in reducing LDL, with tirzepatide 15mg(SUCRA =0.7806) and then semaglutide 2.4mg(SUCRA=0.7260) coming in behind. Naltrexone 32mg/Bupropion 360mg(SUCRA = 0.8757) ranked first followed by tirzepatide(SUCRA=0.8593) in increasing HDL, however the increase was not statistically significant (MD: 0.00, 95%CI: -0.04 to 0.05). Conclusion GLP-1 RAs’ superiority in addressing cardiometabolic parameters that are often deranged in patients with overweight and obesity highlights the need for weight lost medication transitioning from one that decreases and suppresses appetite or prevent the absorption of lipids to one that targets the altered metabolic mileu of patients with overweight and obesity, highlighting the multipronged approach needed to treat this metabolic disease.

A new natural product derived from cyclosorus terminans provides cardiometabolic protection against obese-induced cardiac dysfunction in rats via suppressing mitochondrial dysfunctions and apoptosis

Abstract Background The development of a novel pharmacological target for obesity has long been considered challenging in mitigating the global cardiovascular complications and mortality. Given the cytotoxic effects associated with various anti-obesity drugs, there is growing interest in exploring new natural products as potential sources for bioactive agents to treat obesity-associated diseases with minimal side effects. While Cyclosorus terminans extract has demonstrated anti-diabetic and anti-obese efficacies in adipose-derived stem cells, its cardioprotective effects in high-fat diet (HFD)-induced obese-insulin resistance rat models have never been elucidated. Purpose To examine the effects of long-term Cyclosorus terminans treatment on metabolic, cardiac, and mitochondrial functions and apoptosis in HFD-induced obese-insulin-resistant rat models Methods Male Wistar rats (n=10) were continually fed with HFD and treated with either vehicle (HFV, virgin oil for 2 ml/kg/day, p.o., n=5) or Cyclosorus terminans (HFC, 100 mg/kg/day, p.o., n=5) for 12 weeks. Rats fed a normal diet (NDV, n=5) were used as a control to confirm the development of HFD-induced obesity. The left ventricular ejection fraction (LVEF) and the ratio between early (E) and late atrial (A) ventricular filling velocity were measured using echocardiography, and the homeostatic model assessment for insulin resistance (HOMA-IR) was determined using blood serum. The cardiac tissue was processed to assess mitochondrial reactive oxygen species (ROS) levels, membrane potential (MMP) changes via red/green fluorescence intensity ratio, and apoptotic protein. Results HFV rats became obese and had impaired cardiometabolic function as shown by reducing LVEF, E/A ratio, and increasing HOMA-IR, respectively (Fig. 1A-C). These obese rats also had mitochondrial ROS overproduction, MMP depolarization (reduced red/green ratio), and apoptosis (increased Bax protein expression) (Fig. 1D-F). Treatment with Cyclosorus terminans (HFC) significantly mitigated mitochondrial dysfunction and apoptosis, resulting in cardiometabolic protection in HFD-fed rats (Fig. 1A-F). Conclusion A new natural product derived from Cyclosorus terminans effectively protected the heart against long-term HFD-induced cardiometabolic impairments by reducing mitochondrial dysfunction and apoptosis. These findings demonstrate Cyclosorus terminans as a novel cardiometabolic protection against obesity-related cardiac complications.

Effects of body mass index on worsening of heart failure and all-cause death in patients with heart failure and reduced left ventricular ejection fraction: a 10-year follow-up study

Abstract Background/Introduction Obesity in patients with heart failure (HF) with reduced ejection fraction (HFrEF) is common, and with the emergence of effective anti-obesity drugs, a better understanding of the relation between BMI and clinical outcome in HFrEF is needed. Purpose This study aimed to analyse whether a body mass index (BMI) above 27 kg/m2 (cut-off used in trials) is associated with a greater rate of all-cause death and HF hospitalization in patients with HFrEF. Methods We included 1,017 medically optimized according to existing HF guidelines at the time and clinically stable HF patients with a left ventricular ejection fraction of &amp;lt;45% from the NorthStar study. Patients were included between 2005 and 2009 and followed for 10 years using Danish nationwide registries. The outcomes of interest were all-cause death and hospital discharge for HF (overnight stay). Descriptive statistics were grouped according to tertiles of BMI. The association between BMI as a continuous variable and the outcomes of interest was analysed using restricted cubic splines in Cox proportional-hazards models. Reported were hazard ratios (HR) with 95% confidence intervals (CI) adjusted for relevant prognostic covariates (reference: BMI = 27 kg/m2). Results At enrolment, the median age was 69 years, 75% were men, and the median BMI was 26.3 kg/m2 (Table 1). Patients in the upper 3rd BMI tertile were younger (median age 67), had a lower level of NT-proBNP level (median 737.5 pg/ml) and a higher proportion of diabetes (29.9%). During 10 years of follow-up, HF hospitalization occurred in 683 patients (61.7%), and 623 patients died (56.3%). A BMI above 27 kg/m2 was associated with a higher rate of HF hospitalization (significantly from BMI 35.2 kg/m2: HR 1.30 [CI 1.00-1.68]; Figure 1). Similar findings were observed for all-cause mortality (significantly from BMI 35.7 kg/m2: HR 1.27 [CI 1.00-1.62]) Conclusion In patients with HFrEF, a BMI above 27 kg/m2 was associated with a higher rate of HF hospitalization and all-cause death. Efforts to find effective and safe approaches to reducing weight in obese patients with HFrEF are warranted.Figure 1

Morus alba: natural and valuable effects in weight loss management.

Overweight and obesity are conditions associated with serious comorbidities, such as diabetes and cardiovascular disease. Prevalence of excessive fat accumulation is increasing worldwide, and thus the need for efficient and sustainable weight loss regimes has become a major issue in clinical practice. Despite the important advances in the development of anti-obesity medications (AOM), their side effects, cost, and accessibility, are limiting factors for their routine use. Conversely, the studies of medicinal plants for weight management holds strong promise as a growing area of research. This review consolidates the representative evidence about the beneficial impacts of Morus alba on weight management and associated metabolic parameters, encompassing: inhibition of digestive enzymes, and thus contribution to the energy deficit required for weight loss, improvements in glucose and lipid metabolism, and attenuation of adiposity. Findings from in vitro, in vivo, and clinical investigations reviewed in the paper, demonstrate that white mulberry extracts have the potency to supplement efficiently and safely a healthy weight management approach.