Greater Weight Loss Research Articles

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.

Transcriptomic Analysis of the Protective Effect of Piperine on Orlistat Hepatotoxicity in Obese Male Wistar Rats.

Obesity is a risk factor for the development of noncommunicable diseases that impair the quality of life. Orlistat is one of the most widely used drugs in the management of obesity due to its accessibility and low cost. However, cases of hepatotoxicity have been reported due to the consumption of this drug. On the other hand, piperine is an alkaloid found in black pepper that has demonstrated antiobesity, antihyperlipidemic, antioxidant, prebiotic, and hepatoprotective effects. The aim of this study was to evaluate the protective effect of piperine on the toxicity of orlistat in liver tissue. Obese male rats were administered piperine (30 mg/kg), orlistat (60 mg/kg), and the orlistat-piperine combination (30 mg/kg + 60 mg/kg) daily for 6 weeks. It was observed that the orlistat-piperine treatment resulted in greater weight loss, decreased biochemical markers (lipid profile, liver enzymes, pancreatic lipase activity), and histopathological analysis showed decreased hepatic steatosis and reduction of duodenal inflammation. Transcriptomic analysis revealed that the administration of piperine with orlistat increased the expression of genes related to the beta-oxidation of fatty acids, carbohydrate metabolism, detoxification of xenobiotics, and response to oxidative stress. Therefore, the results suggest that the administration of orlistat-piperine activates signaling pathways that confer a hepatoprotective effect, reducing the toxic impact of this drug.

Predictors of Successful Weight Loss in Extremely Obese Individuals Undergoing Roux-en-Y Gastric Bypass Surgery.

Roux-en-Y gastric bypass (RYGB) is a standard treatment for severe obesity, but some patients do not achieve the expected success in weight loss. The aim of this study was to evaluate possible predictors of weight loss after RYGB. Sixty-three patients were included. Pre- and postoperative data were collected from medical records, including comorbidities, anthropometry, energy/macronutrient intake, and physical activity level (PAL). Variants in the brain-derived neurotrophic factor (BDNF; rs6265) and lysophospholipase like 1 (LYPLAL1; rs4846567) genes were investigated. Excess weight loss (EWL) >50% was considered to be successful weight loss (SWL). Logistic regression models were used to verify predictor variables. Participants' median preoperative body mass index (BMI) was 53 kg/m2 (interquartile range, 46 to 58). At 12 and 24 months after surgery, EWL was 63% and 67%, and the failure rate was 19% and 16%, respectively. The individuals with insufficient weight loss (IWL) after 12 months had higher preoperative weight, BMI, and overweight. At 24 months, lowest frequency of individuals with SWL in the first year was found in the IWL group. No significant differences were found between the groups in dietary intake and PAL. In the logistic regression, high initial BMI was a predictor of the worst response in both periods, and high initial total weight loss was a predictor of a better response at 24 months. The polymorphism analysis did not show differences between groups in either gene. Lower preoperative BMI and greater weight loss at 12 months were predictors of SWL after RYGB.

Weight Changes Are Linked to Adipose Tissue Genes in Overweight Women with Polycystic Ovary Syndrome.

Women with polycystic ovary syndrome (PCOS) have varying difficulties in achieving weight loss by lifestyle intervention, which may depend on adipose tissue metabolism. The objective was to study baseline subcutaneous adipose tissue gene expression as a prediction of weight loss by lifestyle intervention in obese/overweight women with PCOS. This is a secondary analysis of a randomized controlled trial where women with PCOS, aged 18-40 and body mass index (BMI) ≥ 27 were initially randomized to either a 4-month behavioral modification program or minimal intervention according to standard care. Baseline subcutaneous adipose tissue gene expression was related to weight change after the lifestyle intervention. A total of 55 obese/overweight women provided subcutaneous adipose samples at study entry. Weight loss was significant after behavioral modification (-2.2%, p = 0.0014), while there was no significant weight loss in the control group (-1.1%, p = 0.12). In microarray analysis of adipose samples, expression of 40 genes differed significantly between subgroups of those with the greatest weight loss or weight gain. 10 genes were involved in metabolic pathways including glutathione metabolism, gluconeogenesis, and pyruvate metabolism. Results were confirmed by real-time polymerase chain reaction (RT-PCR) in all 55 subjects. Expressions of GSTM5, ANLN, and H3C2 correlated with weight change (R = -0.41, p = 0.002; R = -0.31, p = 0.023 and R = -0.32, p = 0.016, respectively). GSTM5, involved in glutathione metabolism, was the strongest predictor of weight loss, and together with baseline waist-hip ratio (WHR) explained 31% of the variation in body weight change. This study shows that baseline subcutaneous adipose tissue genes play a role for body weight outcome in response to lifestyle intervention in overweight/obese women with PCOS.

Effect of incremental exercise training interventions in a Cardiac Rehabilitation Program following myocardial infarction

Abstract Background Exercise-based cardiac rehabilitation is recommended after myocardial infarction (MI) to improve prognosis, quality of life and control of cardiovascular risk factors. However, the specific impact of different exercise training interventions remains incompletely understood. Purpose To study the health outcomes of three incremental exercise training interventions during a Cardiac Rehabilitation Program (CRP) following MI. Methods We implemented a post-MI Phase 2 CRP in 2022. After initial exercise testing, a 3-month, individualized aerobic and strength ambulatory training program was provided by Cardiologists and Physical Medicine and Rehabilitation physicians (Group 1, n=58). Additionally, a subset of patients received one session of supervised teaching of aerobic and strength training by physiotherapists (Group 2, n=19), and another subset received 8-20 sessions of in-hospital supervised training (Group 3, n=13). Exercise testing was repeated at the end of Phase 2 and peak oxygen consumption (peak VO2) was measured. We analysed quality of life (SF-36), depression (PHQ2), anxiety (GAD2), adherence to Mediterranean diet (PREDIMED) and pharmacological treatment (Morisky-Green), and weekly physical activity (IPAQ). Health outcomes were compared at the beginning and after Phase 2 CRP. Results The cohort comprised 90 patients who completed Phase 2 CRP (mean age 61.2±10.8 years, 84.4% male and 47.8% smokers). Reductions in systolic blood pressure (-10.3±13.8mmHg), LDL cholesterol (-60.7±35.4mg/dL), weight (-2.8±6.6kg, -3±7.8%) and body mass index (-1±2.2) were attained (p<0.05). Smoking abstinence was accomplished in 88.4% of smokers and most patients achieved an LDL<55mg/dL (81.1%). Improvements in quality of life (SF-36 +10.4±19.4 points, p<0.001) and anxiety and depression symptoms (PHQ2 -0.5±1.6 points and GAD2 -0.6±1.6 points, p<0.01) were noted. An increase in peak VO2 (+5.12±5.44ml/kg/min, +23.5±27.4% from baseline, p<0.001) and predicted functional capacity (+13.4±23.8%, p<0.001) was achieved. Patients increased their reported weekly physical activity by 2520.3±2935.4 METS/week (+132% from baseline, p<0.001) and most of them were adherent to Mediterranean diet (91.1%) and pharmacological treatment (95.6%). Patients achieved similar health outcomes regardless of their exercise training group, except for patients in Group 3, who experienced a more pronounced improvement in peak VO2 (+8.1±6.4ml/kg/min, +37.8±34.7% from baseline; p<0.05) and a trend towards higher increase in predicted functional capacity (+21.7±19.2%, p<0.25) and greater weight loss (-5.5±9.4kg, -5.9±9.6%; p<0.2). Conclusions Supervised in-hospital training during a Phase 2 CRP provides superior physical fitness improvements and more pronounced weight loss in MI patients. However, a Phase 2 CRP based on ambulatory training provides similar benefits regarding other health outcomes, such as control of cardiovascular risk factors and quality of life amelioration.Exercise training interventions in a CRP

Exercise-Associated Muscle Cramps in Ironman-Distance Triathletes Over 3 Decades.

This study aimed to explore associations and trends for athletes experiencing exercise-associated muscle cramps (EAMC) in ultraendurance competitions. Retrospective analysis of prospectively collected data. Medical tent data were collected from annual IRONMAN World Championship events. In total, 10 533 medical records were reviewed among 49 530 race participants from 1989 to 2019. Athlete demographics data, performance data, and additional medical conditions were examined. Primary outcome of interest was to compare triathletes with and without EAMC. Secondary outcome was to analyze triathletes with subsequent EAMC. EAMC (N = 2863) occurred in 57.8 per 1000 participants (95% confidence interval = 55.7 to 60.0). The incidence of EAMC did not differ between athlete sex. Athletes with EAMC had greater weight loss but did not differ in serum sodium and serum potassium compared with those without EAMC. Further analysis with a logistic regression analysis revealed that dehydration, exhaustion, hypotension, abdominal pain, headaches, and a previous evaluation for cramping were strongly associated with muscle cramping. The most common treatment for EAMC was intravenous fluids. Findings from the current study support previous reports that electrolyte abnormalities are not associated with cramping. However, our finding that dehydration is associated with muscle cramping contradicts current literature.

Effect of pyloroplasty on clinical outcomes following esophagectomy.

The role of concurrent pyloroplasty with esophagectomy is unclear. Available literature on the impact of pyloroplasty during esophagectomy on complications and weight loss is varied. Data on the need for further pyloric intervention are scarce. Our study compares the clinical outcomes after esophagectomy with or without pyloroplasty and investigates the role of post-operative pyloric dilatation. Consecutive patients (n = 207) undergoing Ivor Lewis esophagectomy performed by two surgeons at our institution were included. Data on patient demographics, mortality rate, anastomotic leak, respiratory complications (Clavien-Dindo grade ≥ 3), anastomotic stricture rate, and percentage weight loss at 1 and 2 year post-operatively were evaluated. For weight analysis at 1 and 2 year post-operatively, patients were excluded if they had been diagnosed with recurrence or died prior to the 1 or 2 year timepoints. Ninety-two patients did not have a pyloroplasty, and 115 patients had a pyloroplasty. There were no complications resulting from pyloroplasty. There was no significant demographic difference between the groups except for age. Mortality rate, anastomotic leak, respiratory complications, anastomotic stricture rate, and percentage weight loss at 1 and 2 years were statistically similar between the two groups. However, 14.1% of patients without pyloroplasty required post-operative endoscopic pyloric balloon dilatation to treat respiratory complications or gastroparesis. Subgroup analysis of patients without pyloroplasty indicated that patients requiring dilatation had greater weight loss at 1 year (15.8% vs 9.4%, p = 0.02) and higher respiratory complications rate (27.3% vs 4.7%, p = 0.038). Overall results from our study that pyloroplasty during Ivor Lewis esophagectomy is safe and useful to prevent the need for post-operative pyloric dilatation.

Malnutrition risk, weight loss, and subsequent survival in patients listed for heart transplantation

BackgroundHigher malnutrition risk is associated with mortality among patients with heart failure and heart transplantation (HT). We investigated which malnutrition risk scores – geriatric nutrition risk index (GNRI), prognostic nutritional index (PNI), or controlling nutritional status (CONUT) – have the strongest mortality association for HT candidates, and whether they are prognostic at the time of HT listing or HT operation. MethodsWe reviewed adults listed for primary HT at a single center 1987–March 2022, with survival follow-up to November 2022. We constructed Cox proportional hazards models and restricted cubic spline curves for each risk score at both HT listing and HT operation and inputted HT operation as a time-varying covariate for models commencing at listing. Risk scores were assessed as continuous and binary variables. Weight change between listing and HT was evaluated similarly. ResultsThe 1024 patients (76% male; median age 55 [46-61] yrs; HT operation n=656) had median follow-up of 4.6 (interquartile range 1.6-8.7) years. As a continuous variable, lower GNRI at HT listing (greater malnutrition risk) was independently associated with higher mortality. As binary variables, higher risk GNRI, PNI or CONUT scores at listing were all associated with higher mortality. Conversely, risk scores at time of HT operation were not associated with subsequent mortality. There was a non-significant trend towards higher mortality with greater weight loss between listing and HT operation. ConclusionMalnutrition risk scores showed prognostic utility only at time of HT listing. As a continuous variable, GNRI at HT listing was independently associated with subsequent mortality.

Weight management medications for chronic use in 37 veterans affairs medical centers-A medication use evaluation.

Controlled trials have demonstrated successful weight loss associated with certain weight management medications (WMMs). However, there are limited real-world data on prescribing patterns and efficacy and safety profiles of WMMs in Veterans Affairs (VA) patients. To evaluate: utilization patterns of WMMs liraglutide, naltrexone/bupropion, orlistat, phentermine, phentermine/topiramate, and semaglutide; weight loss at three, six, twelve, and more than 12 months; safety; and treatment barriers. A retrospective, cross-sectional medication use evaluation (MUE) was conducted using electronic health records of outpatient Veterans newly initiated on WMMs at 37 VA Medical Centers between 1 March 2020 and 31 March 2022. Chart review was used to identify WMM utilization and capture rates of clinical response, defined as 5% and 10% or greater weight loss at the final weight, adverse drug events (ADEs), non-adherence, and discontinuations. Site-specific surveys evaluated local practices and barriers. Among 1959 eligible Veterans, semaglutide, phentermine/topiramate, and orlistat were most frequently prescribed. The clinical response was highest among phentermine/topiramate, liraglutide, and semaglutide. Naltrexone/bupropion and phentermine demonstrated the highest and lowest ADE rates, respectively. Potential barriers to WMM utilization and successful treatment by site reports were drug shortages, patient perceptions of therapeutic course, personal preferences, and VA WMM use criteria. Smaller weight loss and higher discontinuation rates were observed relative to clinical trials. The MUE data allow for better assessment of benefits and risks for Veterans prescribed WMMs.

Efficacy, Safety and Acceptability of a Very-Low-Energy Diet in Adolescents with Obesity: A Fast Track to Health Sub-Study.

The aim of this study was to determine the efficacy, safety and acceptability of a 4-week very-low-energy diet (VLED) program for adolescents with obesity. Adolescents (13-17 years) with obesity and ≥1 obesity-related complication were Fast Track to Health 52-week randomized controlled trial participants. Adolescents undertook a 4-week micronutrient-complete VLED (800 kcal/day), with weekly dietitian support. Anthropometric data were recorded at baseline and week-4 and side-effects at day 3-4, week-1, -2, -3 and -4. Adolescents completed an acceptability survey at week-4. A total of 134 adolescents (14.9 ± 1.2 years, 50% male) had a 5.5 ± 2.9 kg (p < 0.001) mean weight loss at week-4: 95% experienced ≥1 and 70% experienced ≥3 side-effects during the VLED program, especially during the first week. Hunger, fatigue, headache, irritability, loose stools, constipation and nausea were most common. Reporting more side-effects at day 3-4 correlated with greater weight loss at week-4 (r = -0.188, p = 0.03). Adolescents reported 'losing weight' (34%) and 'prescriptive structure' (28%) as the most positive aspects of VLED, while 'restrictive nature' (45%) and 'meal replacement taste' (20%) were least liked. A dietitian-monitored short-term VLED can be implemented safely and is acceptable for many adolescents seeking weight loss, despite frequent side-effects. Investigating predictors of acceptability and effectiveness could determine adolescents most suited to VLED programs.

Exploring Dietary Restraint as a Mediator of Behavioral andCognitive-Behavioral Treatments on Outcomes for Patients With Binge-Eating Disorder With Obesity.

To explore dietary-restraint as a mediator of binge eating and weight-loss outcomes within a randomized controlled trial comparing cognitive-behavioral therapy (CBT) and behavioral weight loss (BWL) for binge-eating disorder (BED) with obesity. Ninety participants were randomly assigned to CBT or BWL and assessed by evaluators blinded to conditions at pretreatment, throughout-, and post-treatment (6 months). Three dietary-restraint measures (Eating Disorder Examination-Questionnaire [EDE-Q]-Restraint, Three-Factor Flexible-Restraint and Rigid-Restraint) were administered at pretreatment and after 2 months of treatment. Regression models examined whether changes at 2-months in the restraint scales mediated the effects of treatment (CBT versus BWL) on binge eating and weight-loss outcomes at post-treatment. CBT and BWL had similar binge-eating outcomes and similar changes in EDE-Q-restraint and flexible-restraint. BWL had greater 2-month increases in rigid-restraint and greater weight-loss at posttreatment than CBT, with results suggesting 2-month changes in rigid-restraint mediated the greater difference (>7 pounds) in weight-loss. The observed mediation effect of 2.92 suggests 39% of total treatment-effect on weight-loss was mediated through 2-month increases in rigid-restraint. This secondary analysis within a trial comparing CBT and BWL for BED suggests early-change in rigid-restraint has a mediating effect of BWL on weight-loss. Findings indicate that BWL improves binge eating and challenge views that dietary-restraint might exacerbate binge eating in BED with obesity. Findings require confirmation using hypothesis-testing in future trials. Clinicaltrials.gov: NCT00537758 ("Treatment for Obesity and Binge Eating Disorder").

Lisdexamfetamine maintenance treatment for binge-eating disorder following successful treatments: randomized double-blind placebo-controlled trial.

Controlled research examining maintenance treatments for responders to acute interventions for binge-eating disorder (BED) is limited. This study tested efficacy of lisdexamfetamine (LDX) maintenance treatment amongst acute responders. This prospective randomized double-blind placebo-controlled single-site trial, conducted March 2019 to September 2023, tested LDX as maintenance treatment for responders to acute treatments with LDX-alone or with cognitive-behavioral therapy (CBT + LDX) for BED with obesity. Sixty-one (83.6% women, mean age 44.3, mean BMI 36.1 kg/m2) acute responders were randomized to LDX (N = 32) or placebo (N = 29) for 12 weeks; 95.1% completed posttreatment assessments. Mixed-models and generalized-estimating equations comparing maintenance LDX v. placebo included main/interactive effects of acute (LDX or CBT + LDX) treatments to examine their predictive/moderating effects. Relapse rates (to diagnosis-level binge-eating frequency) following maintenance treatments were 10.0% (N = 3/30) for LDX and 17.9% (N = 5/28) for placebo; intention-to-treat binge-eating remission rates were 59.4% (N = 19/32) and 65.5% (N = 19/29), respectively. Maintenance LDX and placebo did not differ significantly in binge-eating but differed in weight-loss and eating-disorder psychopathology. Maintenance LDX was associated with significant weight-loss (-2.3%) whereas placebo had significant weight-gain (+2.2%); LDX and placebo differed significantly in weight-change throughout treatment and at posttreatment. Eating-disorder psychopathology remained unchanged with LDX but increased significantly with placebo. Acute treatments did not significantly predict/moderate maintenance-treatment outcomes. Adults with BED/obesity who respond to acute lisdexamfetamine treatment (regardless of additionally receiving CBT) had good maintenance during subsequent 12-weeks. Maintenance lisdexamfetamine, relative to placebo, did not provide further benefit for binge-eating but was associated with significantly better eating-disorder psychopathology outcomes and greater weight-loss.

Effects of time-restricted eating and low-carbohydrate diet on psychosocial health and appetite in individuals with metabolic syndrome: A secondary analysis of a randomized controlled trial

Background & aimsTime-restricted eating (TRE) and low-carbohydrate diet (LCD) can improve multiple cardiometabolic parameters in patients with metabolic syndrome (MetS), but their effects on psychosocial health and satiety are unclear. In this study, we aimed to evaluate the effects of TRE, LCD, and their combination (TRE+LCD) on quality of life (QoL), sleep, mood, appetite, and metabolic hormones in patients with MetS. MethodsThis is a secondary analysis of a single-center, 3-month, open-label, randomized clinical trial investigating the effects of TRE, LCD, and TRE+LCD on weight and cardiometabolic parameters in individuals with MetS. This secondary analysis examined QoL, sleep, mood, and appetite using the Rand 36-Item Short Form (SF-36); Pittsburgh Sleep Quality Index (PSQI); Depression, Anxiety, and Stress Scale; and Eating Behavior Rating Scale, respectively, as well as measured levels of metabolic hormones including leptin, amylin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1 (GLP-1), pancreatic polypeptide (PP), and peptide YY. Between-group comparisons were conducted via one-way ANOVAs and post hoc LSD tests for normally distributed variables or Kruskal‒Wallis H tests and the Nemenyi test for abnormally distributed variables. P < 0.017 was considered significant in multiple comparisons following Bonferroni adjustment. ResultsA total of 162 participants (mean [SD] age, 41.2 [9.9] years; mean [SD] body mass index, 29.3 [3.4] kg/m2; 102 [63%] men) who started the intervention were analyzed. After 3 months, only the TRE group decreased GLP-1 levels (-0.9 [95% CI, -1.9 to -0.3] pg/mL; P = 0.002), increased PP levels (8.9 [95% CI, -7.6 to 71.8] pg/mL; P = 0.011), physical functioning in the SF-36 (5.2 [95% CI, 1.9 to 8.5]; P = 0.001), social functioning in the SF-36 (9.1 [95% CI, 2.5 to 15.6]; P = 0.005), role-physical in the SF-36 (24.1 [95% CI, 11.8 to 36.4]; P < 0.001), role-emotional in the SF-36 (22.4 [95% CI, 12.6 to 32.2]; P < 0.001), and sleep efficiency in the PSQI (0.29 [95% CI, 0.03 to 0.55]; P = 0.021). Compared with changes in LCD, TRE further increased general health in the SF-36 (9.7 [95% CI, 3.3 to 16.0]; P = 0.006). Relative to the changes of TRE+LCD, TRE significantly increased role-emotional in the SF-36 (19.9 [95% CI 4.9 to 34.8]; P = 0.006). Changes in sleep quality, mood status, appetite, and metabolic hormones did not differ among three groups. Greater weight loss was associated with decreased leptin levels (r = 0.538), decreased amylin levels (r = 0.294), reduced total appetite scores (r = 0.220), and improved general health (r = -0.253) (all P ≤ 0.01). ConclusionsTRE, LCD, and TRE+LCD all could improve psychosocial health and reduce appetite. Notably, TRE yielded greater benefits in QoL compared with LCD or TRE+LCD in individuals with MetS. Trial registrationClinicalTrials.gov Identifier: NCT04475822.

Effect of Semaglutide on Cardiac Structure and Function in Patients With Obesity-Related Heart Failure

BackgroundObesity is associated with adverse cardiac remodeling and is a key driver for the development and progression of heart failure (HF). Once-weekly semaglutide (2.4 mg) has been shown to improve HF-related symptoms and physical limitations, body weight, and exercise function in patients with obesity-related heart failure with preserved ejection fraction (HFpEF), but the effects of semaglutide on cardiac structure and function in this population remain unknown. ObjectivesIn this echocardiography substudy of the STEP-HFpEF Program, we evaluated treatment effects of once-weekly semaglutide (2.4 mg) vs placebo on cardiac structure and function. MethodsEchocardiography at randomization and 52 weeks was performed in 491 of 1,145 participants (43%) in the STEP-HFpEF Program (pooled STEP-HFpEF [Semaglutide Treatment Effect in People with Obesity and HFpEF] and STEP-HFpEF DM [Semaglutide Treatment Effect in People with Obesity, HFpEF, and Type 2 Diabetes] trials). The prespecified primary outcome was change in left atrial (LA) volume, with changes in other echocardiography parameters evaluated as secondary outcomes. Treatment effects of semaglutide vs placebo were assessed using analysis of covariance stratified by trial and body mass index, with adjustment for baseline parameter values. ResultsOverall, baseline clinical and echocardiographic characteristics were balanced among those receiving semaglutide (n = 253) and placebo (n = 238). Between baseline and 52 weeks, semaglutide attenuated progression of LA remodeling (estimated mean difference [EMD] in LA volume, −6.13 mL; 95% CI: −9.85 to −2.41 mL; P = 0.0013) and right ventricular (RV) enlargement (EMD in RV end-diastolic area: −1.99 cm2; 95% CI: −3.60 to −0.38 cm2; P = 0.016; EMD in RV end-systolic area: −1.41 cm2; 95% CI: −2.42 to −0.40] cm2; P = 0.0064) compared with placebo. Semaglutide additionally improved E-wave velocity (EMD: −5.63 cm/s; 95% CI: −9.42 to −1.84 cm/s; P = 0.0037), E/A (early/late mitral inflow velocity) ratio (EMD: −0.14; 95% CI: −0.24 to −0.04; P = 0.0075), and E/e′ (early mitral inflow velocity/early diastolic mitral annular velocity) average (EMD: −0.79; 95% CI: −1.60 to 0.01; P = 0.05). These associations were not modified by diabetes or atrial fibrillation status. Semaglutide did not significantly affect left ventricular dimensions, mass, or systolic function. Greater weight loss with semaglutide was associated with greater reduction in LA volume (Pinteraction = 0.033) but not with changes in E-wave velocity, E/e′ average, or RV end-diastolic area. ConclusionsIn the STEP-HFpEF Program echocardiography substudy, semaglutide appeared to improve adverse cardiac remodeling compared with placebo, further suggesting that treatment with semaglutide may be disease modifying among patients with obesity-related HFpEF. (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity [STEP-HFpEF]; NCT04788511; Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes [STEP-HFpEF DM]; NCT04916470)

Improving textile waste biodegradation through fungal inoculation

Textile waste currently contributes about 780,000 tonnes of waste to landfill in Australia alone. Within landfill, biodegradable textiles take multiple years to decompose and most synthetic textiles are effectively not biodegradable. Blends of these fiber types are currently too costly to separate and recycle. Decomposition depends on the presence of suitable microorganisms already present in the landfill. This study aimed to investigate which fungi could best be used to pre-inoculate textile waste entering landfill (to reduce volume) or in a composting system (to recover non-biodegradable materials for re-use). Ten textiles were inoculated with 14 fungi well known for their degradative ability and incubated at 25–30°C for 1–2 months. Greatest weight losses (100 %) were achieved by Chaetomium globosum (Ascomycota), Trametes versicolor and Ganoderma species (Basidiomycota). In textiles with mixtures of cellulose with polyester or elastane, only the cellulose fibers were degraded and the other fiber types were left available for recycling. These results suggest that pre-inoculation with the most effective fungi could increase the rate of decay in cellulosic portions of textiles discarded into landfill, at the least reducing textile volumes quickly. Alternatively, aerobic fermentation of textile waste could recover non-biodegradable synthetic fibers for re-processing and re-use in a low-cost and environmentally benign manner, reducing the need for its manufacture de novo from petroleum derivatives.

Semaglutide: An emerging treatment option for patients with obesity related HFpEF.

Dear Madam, Heart failure is a key contributor to patient morbidity and mortality and affects a staggering 64 million individuals around the globe1. An important sub-phenotype of heart failure is HFpEF, which is characterised by a left ventricular ejection fraction (LVEF) of 50 per-cent. Alarmingly, the incidence of this subtype has been rising globally, making the need for new treatment options extremely crucial2. Initially, the use of Semaglutide, a glucagon-like peptide-1 receptor agonist, showed favourable outcomes in cardiac function of mice. This study observed that weight loss achieved using Semaglutide was met with improvements in several factors associated with HFpEF (reduced LV hypertrophy and fibrosis, improved diastolic function, reduced lung congestion and improved exercise capacity) as compared to weight loss achieved through simple dietary means3. A step further in this direction is a clinical trial that shows that a weekly dosage of 2.4mg of Semaglutide in obesity related HFpEF patients is associated with significantly reduced symptoms and physical limitations, improved exercise function and greater weight loss than placebo4. Of the several parameters observed, improvements in CSS (Clinical Survey Score) of KCCQ (Kansas City Cardiomyopathy Questionnaire) and six minute walking distance were the most clinically meaningful. These promising findings are of particular value to Pakistani population, which has been prey to obesity and HF owing to Westernised eating habits, sedentary lifestyles and fewer healthcare facilities. In addition, South Asians have more fat content per BMI as compared to their white counterparts which coupled with the rising trends in NCD risks in South Asia5, are an immediate call for innovation in therapeutics. Semaglutide, considering its array of cardiometabolic benefits, may provide our doctors with a chance to step away from prescribing long lists of medications that are conventionally given to HF patients for symptom improvement. In a low- income country like Pakistan, this will ensure a better drug compliance and reduced disease burden. It is high time that we tap into the potential of Semaglutide and test its efficacy of it in our native population and take strides in ensuring its easy availability.

What is the effect of bariatric surgery on health-related quality of life in people with obesity? observational cohort analysis of the United Kingdom national bariatric surgery registry.

Previous small studies investigating health-related quality of life (HRQoL) following bariatric surgery have demonstrated heterogenous effects. This study aimed to use National Bariatric Surgery Registry (NBSR) records to investigate the relationship between weight and HRQoL in people undergoing bariatric surgery in the UK. In this observational study using United Kingdom National Bariatric Surgery Registry (NBSR) records between 1st June 2017 and 23rd November 2022, patients undergoing primary bariatric surgery with one baseline and at least one follow-up visit within one year from surgery were eligible for inclusion. Models estimated the relationship between EuroQol Five Dimension 5-level (EQ-5D) and BMI at baseline and longitudinally. Further analyses stratified by type 2 diabetes, type of operation (adjustable gastric band, sleeve, or bypass) and domain of EQ-5D. 5,587 observations of 2,160 patients were analysed. At baseline, mean BMI was 45.7±7.8kg/m2 and mean EQ-5D was 0.78±0.22. A 1kg/m2 higher BMI was associated with 0.005 (95%CI[-0.006,-0.004]) lower EQ-5D. In the month following surgery, EQ-5D increased to 0.91±0.2 while BMI decreased to 39.8±7.1kg/m2 (P<0.001 for both); subsequently EQ-5D plateaued (0.90±0.17 at 12 months) while BMI continued to decrease (31.5±6.2kg/m2 at 12 months, P<0.001). Each 1kg/m2 decrease in BMI was associated with a 0.006 (95%CI [-0.007,-0.005]) increase in EQ-5D. Remission of T2D was independently associated with increase in EQ-5D (0.037, 95%CI [0.015,0.059]); type of operation was not. Decreases in BMI were associated with improvements in all five domains of EQ-5D. In this large dataset, greater weight loss and T2D remission were independently associated with greater improvements in HRQoL following bariatric surgery. The HRQoL-BMI relationship for people undergoing bariatric surgery differs to that which has previously been estimated following behavioural interventions. Use of the estimates generated here will be important for clinical and political decision making.

Incidence of new onset type 2 diabetes in adults living with obesity treated with tirzepatide or semaglutide: real world evidence from an international retrospective cohort study

Tirzepatide, a novel dual agonist of glucagon-like-peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), has demonstrated greater magnitude of weight loss compared to semaglutide in a phase 3 clinical trial. However, the effect of tirzepatide on incidence of type 2 diabetes (T2D) in individuals with overweight and obesity, and the effect on major adverse cardiovascular outcomes in individuals with pre-existing T2D, remains unknown. We performed a retrospective cohort study of anonymised electronic medical records using the TriNetX network (TriNetX LLC, Cambridge, MA, USA) a global federated database. The data used in this study was collected on 5th June 2024. Two cohorts of individuals were generated: 1) without pre-existing T2D and, 2) with T2D. We adopted an active comparator new user design on new initiations of either tirzepatide or semaglutide therapy. Analysis began from the index event which was defined as individuals on respective therapy for 6 months only. Analysis of outcomes was conducted off-drug, in individuals without a pre-existing history of the disease of interest. Individuals were followed up for 12 months post the index event. Primary outcome for cohort 1 was incidence of T2D, and for cohort 2 was composite: all-cause mortality, cerebral infarction, acute coronary syndrome, and heart failure. Secondary outcomes for cohort 1 were change in HbA1c and body weight and for cohort 2: incidence of micro- and macrovascular complications, suicidal ideation and/or attempt, and all-cause mortality. We propensity score matched (1:1) for potential confounders: baseline demographics, socioeconomic circumstances, HbA1c, weight, relevant co-morbidities, and anti-obesity, hypoglycaemic and cardioprotective agents. The study population without T2D consisted of 13,846 individuals, equally split between tirzepatide and semaglutide users. Tirzepatide was associated with both lower risk for incident T2D (HR 0.73, 95% CI 0.58-0.92, p<0.001) and greater weight loss (-7.7kg, [95% CI-6.8,-8.5kg], p<0.001), compared to semaglutide (-4.8kg, [95% CI-3.9,-5.6kg], p<0.001). In individuals with pre-existing T2D (n=8446), tirzepatide was associated with lower risk of the composite outcome (HR 0.54, 95% CI 0.38-0.76, p<0.001), cerebral infarction (HR 0.45, 95% CI 0.24-0.84, p=0.010) and all-cause mortality (HR 0.33, 95% CI 0.15-0.73, p=0.004) compared to semaglutide. Tirzepatide is associated with significantly reduced risk of developing T2D and major adverse cardiovascular events in individuals living with obesity and T2D respectively. Randomised controlled trials investigating the utility of dual incretin agonists in the primary prevention of T2D and cardiovascular disease in higher risk populations are now required. Nil.

Comparative study of Laparoscopic Sleeve Gastrectomy versus Laparoscopic Single Anastomosis Sleeve Ileal Bypass (SASI) as a Treatment Modality for Morbidly Obese Patients with Type 2 Diabetes Mellitus

Abstract Background Bariatric surgery has been shown to be the most successful approach in managing morbid obesity that can achieve and sustain great weight loss for a long period. Furthermore, bariatric surgery can achieve better resolution of type 2 diabetes mellitus (T2DM) than intensive medical therapy alone. The present study aimed to compare the effect of Sleeve Gastrectomy (SG) against Single Anastomosis Sleeve Ileal Bypass (SASI) regarding the control of Diabetes Mellitus and weight loss. Patients and Methods This is a prospective comparative study conducted on 60 obese patients (BMI of 30 kg/m2 associated with obesity-related comorbidities including T2DM) to evaluate the effect of SG Versus SASI on obese patients with type II DM. it was carried out in Misr University Hospital from January 2022 to June 2022. This study included 60 patients which are divided randomly into two groups; one group consisted of 30 patients underwent SASI, the other group consisted of 30 patients underwent SG. The main outcome measures were excess weight loss (EWL) and resolution of T2DM at 6 after surgery. Results The results of this study showed that there was no statistically significant difference between both groups regarding EWL (the mean EWL % was 47.39±8.07 &amp; 48.09 ±1.4 for SASI &amp; SG respectively). Improvement in T2DM after SASI was better than SG (80% vs 66.7%, respectively) with no statistically difference between them. SASI required longer operative time than SG (116.83±19.23 versus 60.5 ±9.77, respectively). Complications occurred in 2 (6.7%) patients after SASI and 5 (16.7%) patients after SASI. Conclusion There was a statistically significant effect of SASI and SG on morbidly obese patients with T2DM; improving both obesity and obesity related co- morbidities with no statically significant difference between both groups regarding EWL and Improvement in T2DM after 6 months. So, large sample size with long-term follow-up period should be performed to better evaluate these technical surgeries and their efficacy regarding postoperative weight loss, metabolic changes, and nutritional status of patients.

Changes in Basal and Bolus Insulin Requirements with Tirzepatide as an Adjunctive Therapy in Adults with Type 1 Diabetes Using Tandem Control-IQ.

This study was aimed at investigating changes in insulin requirements and glycemic outcomes in adults with type 1 diabetes (T1D) using Control IQ (Tandem Diabetes) automated insulin delivery system (AID) over 8months of tirzepatide treatment. In this single-center, observational study, we collected demographic, A1c, weight, sensor glucose, and insulin dose data for adults with T1D who were using AID and initiated tirzepatide adjunct therapy for clinical indications (n = 11, median age 37, 64% female and mean body mass index of 39.6kg/m2). Data were compared from baseline and over 8months. Within 2months of tirzepatide treatment, there were significant reductions in total daily insulin [median (IQR) 73.9 (47.6-95.8) to 51.7 (46.7-66.8) units/day, p < 0.001], basal insulin [47 (28.2-51.8) to 32.4 (25.5-46.3) units/day, p < 0.001], and bolus insulin [31.4 (19.9-38.3) to 17.9 (14.9-22.2) units/day, p < 0.001] requirements. Insulin dose reduction from 2 to 8months was modest. The frequency of user-initiated boluses did not differ throughout the study. Despite reductions in total insulin requirement, time in range (70-180mg/dl) increased by 7%, A1c reduced by 0.5%, weight reduced by 9%, without increase in time below 70mg/dl. This pilot study provides clinical guidance on insulin titration for adults with T1D who may initiate tirzepatide therapy. Based on the findings of this study, we recommend reducing 25% of total daily insulin dose at tirzepatide initiation in adults with T1D using AID with baseline A1c of less than 7.5%. Higher doses of tirzepatide were associated with greater weight loss, however, the reduction in insulin requirement was minimal.