Percentage Change In Body Weight Research Articles

Tirzepatide for Obesity Treatment and Diabetes Prevention.

Obesity is chronic disease and causal precursor to myriad other conditions, including type 2 diabetes. In an earlier analysis of the SURMOUNT-1 trial, tirzepatide was shown to provide substantial and sustained reductions in body weight in persons with obesity over a 72-week period. Here, we report the 3-year safety outcomes with tirzepatide and its efficacy in reducing weight and delaying progression to type 2 diabetes in persons with both obesity and prediabetes. We performed a phase 3, double-blind, randomized, controlled trial in which 2539 participants with obesity, of whom 1032 also had prediabetes, were assigned in a 1:1:1:1 ratio to receive tirzepatide at a once-weekly dose of 5 mg, 10 mg, or 15 mg or placebo. The current analysis involved the participants with both obesity and prediabetes, who received their assigned dose of tirzepatide or placebo for a total of 176 weeks, followed by a 17-week off-treatment period. The three key secondary end points, which were controlled for type I error, were the percent change in body weight from baseline to week 176 and onset of type 2 diabetes during the 176-week and 193-week periods. At 176 weeks, the mean percent change in body weight among the participants who received tirzepatide was -12.3% with the 5-mg dose, -18.7% with the 10-mg dose, and -19.7% with the 15-mg dose, as compared with -1.3% among those who received placebo (P<0.001 for all comparisons with placebo). Fewer participants received a diagnosis of type 2 diabetes in the tirzepatide groups than in the placebo group (1.3% vs. 13.3%; hazard ratio, 0.07; 95% confidence interval [CI], 0.0 to 0.1; P<0.001). After 17 weeks off treatment or placebo, 2.4% of the participants who received tirzepatide and 13.7% of those who received placebo had type 2 diabetes (hazard ratio, 0.12; 95% CI, 0.1 to 0.2; P<0.001). Other than coronavirus disease 2019, the most common adverse events were gastrointestinal, most of which were mild to moderate in severity and occurred primarily during the dose-escalation period in the first 20 weeks of the trial. No new safety signals were identified. Three years of treatment with tirzepatide in persons with obesity and prediabetes resulted in substantial and sustained weight reduction and a markedly lower risk of progression to type 2 diabetes than that with placebo. (Funded by Eli Lilly; SURMOUNT-1 ClinicalTrials.gov number, NCT04184622.).

Impact of thermal processing on phytochemical profile and cardiovascular protection of Beta vulgaris L. in hyperlipidemic rats.

Beetroot (Beta vulgaris L.) is globally recognized for its outstanding color and flavor. It has been acknowledged for its therapeutic value since the ancient Romans. It is used to treat cardiovascular disorders. The therapeutic benefits of red beetroot are due to the substantial amounts of various bioactive metabolites, such as ascorbic acid, carotenoids, nitrates, phenolics, and betalains. However, the bioavailability and shelf life of these substances are significantly affected by the considerable variations in their processing methods among different countries. The longevity of the extracts is prolonged by employing well-established preservation techniques, such as boiling and steaming, which involve the application of heat. Our study aimed to analyze and compare the phytochemical composition of raw and heat processed beetroot using UPLC-QTOF-MS/MS. In addition, the study aimed to assess the effectiveness of processed beetroot in protecting against cardiovascular complications in a rat model of obesity induced by high-fat diet (HFD). UPLC-QTOF-MS/MS phytochemical profiling revealed the presence of 51 compounds, including organic acids, flavonoids, phenolics, betanins, and saponins. All the extracts demonstrated a significant decline in MDA, TNF- α, and IL-6 levels, suppressed the TGF-β expression, and restored the serum catalase level to normal. Among all the tested extracts, the steamed extract exhibited the slightest percentage change in body weight (10.2 ± 6.4) and effectively lowered the TNF-α level to normal levels. In contrast, the normal histological structure of heart muscle fibers was notably preserved in the cardiac sections of rats pretreated with steamed and boiled beetroot extracts. Additionally, mild caspase-3 immunoreactivity was observed in the cardiac muscles. The current study demonstrated that the steamed beetroot extract showed improved cardioprotective properties compared to the fresh and boiled extracts.

Survodutide for treatment of obesity: rationale and design of two randomized phase 3 clinical trials (SYNCHRONIZE™-1 and -2).

The objective of this study was to describe the rationale and design of two multinational phase 3 clinical trials of survodutide, an investigational glucagon and glucagon-like peptide-1 receptor dual agonist for the treatment of obesity with or without type 2 diabetes (T2D; SYNCHRONIZE-1 and -2). In these ongoing double-blind trials, participants were randomized to once-weekly subcutaneous injections of survodutide or placebo added to lifestyle modification. Survodutide doses are uptitrated to 3.6 or 6.0 mg, and dose flexibility is permitted. Participants (n = 726) in SYNCHRONIZE-1 (NCT06066515) have a baseline BMI ≥ 30 kg/m2 or ≥27 kg/m2 with at least one obesity-related complication but without T2D; participants (n = 755) in SYNCHRONIZE-2 (NCT06066528) have a baseline BMI ≥ 27 kg/m2 and T2D. The primary endpoints are percentage change in body weight and proportion of participants achieving ≥5% body weight reduction from baseline to week 76. Secondary endpoints include change in systolic blood pressure and measures of glycemia. A SYNCHRONIZE-1 substudy is evaluating changes in body composition and liver fat content using magnetic resonance imaging. These trials are designed to provide robust evaluation of the efficacy, safety, and tolerability of survodutide for the treatment of obesity in the presence or absence of T2D.

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.

Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis

BackgroundWeight reduction has been shown to alleviate symptoms of osteoarthritis of the knee, including pain. The effect of glucagon-like peptide-1 receptor agonists on outcomes in knee osteoarthritis among persons with obesity has not been well studied.MethodsWe conducted a 68-week, double-blind, randomized, placebo-controlled trial at 61 sites in 11 countries. Participants with obesity (a body-mass index [BMI; the weight in kilograms divided by the square of the height in meters] of ≥30) and a clinical and radiologic diagnosis of moderate knee osteoarthritis with at least moderate pain were randomly assigned, in a 2:1 ratio, to receive once-weekly subcutaneous semaglutide (2.4 mg) or placebo, in addition to counseling on physical activity and a reduced-calorie diet. The primary end points were the percentage change in body weight and the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score (on a scale of 0 to 100, with higher scores reflecting worse outcomes) from baseline to week 68. A key confirmatory secondary end point was the physical-function score on the 36-Item Short Form Health Survey (SF-36), version 2 (on a scale of 0 to 100, with higher scores indicating greater well-being).ResultsA total of 407 participants were enrolled. The mean age was 56 years, the mean BMI 40.3, and the mean WOMAC pain score 70.9. A total of 81.6% of the participants were women. The mean change in body weight from baseline to week 68 was −13.7% with semaglutide and −3.2% with placebo (P<0.001). The mean change in the WOMAC pain score at week 68 was −41.7 points with semaglutide and −27.5 points with placebo (P<0.001). Participants in the semaglutide group had a greater improvement in SF-36 physical-function score than those in the placebo group (mean change, 12.0 points vs. 6.5 points; P<0.001). The incidence of serious adverse events was similar in the two groups. Adverse events that led to permanent discontinuation of the trial regimen occurred in 6.7% of the participants in the semaglutide group and in 3.0% in the placebo group, with gastrointestinal disorders being the most common reason for discontinuation.ConclusionsAmong participants with obesity and knee osteoarthritis with moderate-to-severe pain, treatment with once-weekly injectable semaglutide resulted in significantly greater reductions in body weight and pain related to knee osteoarthritis than placebo. (Funded by Novo Nordisk; STEP 9 ClinicalTrials.gov number, NCT05064735.)

Loss of body weight is dose-dependently associated with reductions in symptoms of hip osteoarthritis.

While weight loss is recommended for managing hip osteoarthritis (OA), most evidence comes from knee OA studies, limiting its applicability to hip OA. This study addresses this gap by examining the effects of weight loss on hip OA symptoms. A retrospective audit of routinely collected healthcare data from participants enrolled in the Osteoarthritis Healthy Weight for Life (OAHWFL) program, designed for individuals with knee or hip OA. In total, 1714 adults with hip OA were selected from the OAHWFL program; 1408 completed the initial 18-week weight loss phase, while 306 did not complete it. After 18 weeks, participants transitioned to an indefinite weight maintenance phase. Percentage change in body weight from baseline at 18 weeks. Changes in the five subscales of the Hip Disability and Osteoarthritis Outcome Score (HOOS) (Pain, Activity Limitations in Daily Living, Stiffness and Range of Motion, Sports and Recreation Function, and Hip-related Quality of Life) from baseline to 18 weeks. Linear regression, adjusted for sex and baseline values of age, weight, and respective HOOS scores, assessed the relationship between percentage weight change (analyzed as both a continuous variable and in categories: ≤2.5%, >2.5-5.0%, >5.0-7.5%, >7.5-10%, and >10% of baseline weight) and changes in all five HOOS subscales. At baseline, participants had a mean age of 65.14 years, 70% were female, and 78% were individuals with obesity (Body Mass Index ≥30 kg/m2). A statistically significant dose-response relationship was observed between weight loss and improvements in all HOOS subscales, with the greatest improvement in the Hip-related Quality of Life subscale (14.42 points, 31.14%) for >10% weight loss. Our findings suggest that weight loss is associated with reduced symptoms of hip OA, supporting weight loss as an effective treatment strategy for hip OA.

6926 Subgroup Analysis by Gender and Body Mass Index (BMI) in People Living With Overweight/Obesity in the Survodutide, a Glucagon/GLP-1 Receptor Dual Agonist, Phase II Trial

Abstract Disclosure: C.W. Le Roux: Consulting Fee; Self; Boehringer Ingelheim, Novo Nordisk, GI Dynamics, Herbalife, Johnson &amp; Johnson, Eli Lilly, Keyron. O. Steen: Consulting Fee; Self; Eli Lilly &amp; Company, Novo Nordisk, Sanofi. Grant Recipient; Self; Alnylam, Anji, AstraZeneca, Boehringer Ingelheim, Eli Lilly &amp; Company, Janssen, Genzyme Corporation, Medacorp, Novo Nordisk, Medicago, Moderna, Novavax, Pfizer, Sanofi, Zucara Therapeutics, Gilead, ViaCyte, CRISPR Therapeutics, Kowa. Speaker; Self; Amgen Inc, AstraZeneca, Bausch Health, Janssen, LMC, Novo Nordisk. K.J. Lucas: None. E. Startseva: Employee; Self; Boehringer Ingelheim. A. Unseld: Employee; Self; Boehringer Ingelheim. A.M. Hennige: Employee; Self; Boehringer Ingelheim. Aim: To explore the effect of gender and BMI on weight loss and adverse events with survodutide in people living with overweight/obesity. Methods: In this double-blind, placebo (PBO)-controlled Phase II trial (NCT04667377), 387 adults with BMI ≥27 kg/m2 without diabetes were randomized 1:1:1:1:1 to weekly subcutaneous survodutide (0.6, 2.4, 3.6, 4.8 mg) or PBO over 46 weeks. Percentage change in body weight (primary endpoint), absolute change in body weight and waist circumference (secondary endpoints), and adverse events (AEs) were assessed in subgroups based on gender and BMI at baseline (BL). Data were analyzed descriptively for all participants who received ≥1 dose of study drug and had data for ≥1 efficacy endpoint (full analysis set [FAS]; planned treatment: n=384). Results: Of 384 participants, 68.2% (262) were female. At BL, 9.9% (38), 30.5% (117), 31.8% (122), and 27.9% (107) had a BMI of &amp;lt;30, 30-&amp;lt;35, 35-&amp;lt;40, and ≥40 kg/m2, respectively. Demographics and clinical characteristics at BL were similar between males and females and across BMI subgroups. At Week 46, mean percentage change in body weight from BL with survodutide 4.8 mg vs PBO was -11.9% vs -3.3% in males and -17.0% vs -3.2% in females, and -19.1% vs -1.7%, -15.8% vs -3.1%, -15.4% vs -5.8%, and -13.4% vs -0.8% across BL BMI categories. Mean absolute body weight loss from BL (survodutide 4.8 mg vs PBO) was -15.9 vs -4.2 kg in males and -22.0 vs -3.0 kg in females. Reductions in absolute body weight with survodutide 4.8 mg vs PBO were similar across BMI subgroups: -21.3 vs 1.4 kg, -16.2 vs -3.3 kg, -22.2 vs -7.5 kg, and -19.9 vs -1.6 kg. Mean absolute change in waist circumference from BL (survodutide 4.8 mg vs PBO) was -12.8 vs -1.7 cm in males and -17.9 vs -4.9 cm in females, and -8.4 vs -2.6 cm, -14.3 vs -6.4 cm, -17.5 vs -5.0 cm, and -17.2 vs 3.3 cm across BL BMI categories. A higher proportion of participants lost ≥15% of BL body weight with survodutide 4.8 mg vs PBO: 31.8% vs 9.5% in males and 66.7% vs 3.0% in females, and 75.0% vs 14.3%, 57.9% vs 4.5%, 52.0% vs 6.7%, and 50.0% vs 0.0% across BL BMI categories; respectively. All survodutide doses (pooled) were tolerated as expected across gender and BL BMI subgroups. In males vs females, respectively, rates of any AE (87.9% vs 92.4%), serious AEs (4.0% vs 4.3%), and discontinuations due to AEs (25.3% and 24.3%) were comparable. Gastrointestinal (GI) AEs with all survodutide doses were experienced by fewer males (65.7%) than females (79.5%); mild to moderate nausea was the most frequently reported GI AE in both subgroups. Conclusion: After 46 weeks of survodutide treatment, females appeared to lose more body weight and waist circumference than males. Participants with a lower vs higher BL BMI generally lost more proportional body weight, with an opposite trend observed for waist circumference. Presentation: 6/2/2024

Seven glucagon-like peptide-1 receptor agonists and polyagonists for weight loss in patients with obesity or overweight: an updated systematic review and network meta-analysis of randomized controlled trials

PurposeThis study aimed to provide evidence-based support and a reference for the efficacy and safety of seven glucagon-like peptide-1 (GLP-1) receptor agonists and polyagonists for weight loss in patients with obesity or overweight through a network meta-analysis. MethodsRelevant randomized controlled trials (RCTs) with an intervention duration of at least 16 weeks assessing seven GLP-1 receptor agonists and polyagonists (mazdutide, 6 or 4.5 mg; retatrutide, 12 or 8 mg; tirzepatide, 15 or 10 mg; liraglutide, 3.0 mg; semaglutide, 2.4 mg; orforglipron, 45 or 36 mg; and beinaglutide, 0.2 mg) in patient with obesity or overweight was searched using three databases (Cochrane Library, PubMed, and Embase) from creation to August 30, 2024. The primary outcome was the percentage change in body weight from baseline. Secondary outcomes included changes in waist circumference, hemoglobin A1c, and fasting plasma glucose level from baseline; adverse events, serious adverse events, adverse event withdrawal, and hypoglycemic events. We conducted a frequentist random-effects network meta-analysis to analyze the data extracted from the RCTs using Stata 16.1 software. ResultsTwenty-seven RCTs of seven GLP-1 receptor agonists and polyagonists and 15,584 patients were included in the network meta-analysis. In terms of efficacy, compared with placebo, retatrutide 12 mg (−22.10 % in body weight and − 17.00 cm in waist circumference), retatrutide 8 mg (−20.70 % and − 15.90 cm), and tirzepatide 15 mg (−16.53 % and − 13.23 cm) were the three most efficacious treatments for reducing body weight and waist circumference. However, these treatments were less effective in patients with type 2 diabetes mellitus (T2DM). In addition, patients with a high body mass index (BMI) or longer treatment cycles exhibited significantly greater weight loss than those with a low BMI or shorter treatment cycles. In terms of safety, patients without T2DM had a higher incidence of adverse events than those with T2DM. None of the interventions increased the incidence of serious adverse or hypoglycemic events (˂54 mg/dL). There was no significant difference in the incidence of adverse event withdrawal for all interventions in head-to-head comparisons. In addition, disparities in race, BMI, and treatment cycles did not significantly increase the incidence of adverse events. Finally, the sensitivity and publication bias analyses indicated that the basic analysis results were reliable. ConclusionRetatrutide (both doses) and tirzepatide exhibited superior efficacy compared to other GLP-1 receptor agonists and polyagonists in reducing body weight and waist circumference. Patients without T2DM, those with a high BMI, and individuals undergoing longer treatment cycles demonstrated significantly greater weight loss and reductions in waist circumference. Dual or triple receptor agonists (GLP-1 plus glucose-dependent insulinotropic polypeptide and/or Glucagon receptor) are more effective for weight loss than GLP-1 receptor agonists.

Topiramate added to metformin for obesity control in women with polycystic ovary syndrome: a randomized clinical trial.

Polycystic ovary syndrome (PCOS) is often linked with obesity, and weight management can improve endocrine and cardiometabolic features. To evaluate the effects of adding topiramate (TPM) to metformin (MTF) on weight control, hormonal and metabolic outcomes in women with PCOS. In a randomized, double-blind, placebo-controlled trial, participants with PCOS and body mass index ≥30 kg/m² or ≥27 kg/m² associated with hypertension, type 2 diabetes, or dyslipidemia followed a 20 kcal/kg diet in addition to 850 mg of MTF or a previous MTF regimen. They were randomized to receive either TPM or placebo (P) alongside MTF. Anthropometric measurements, blood pressure, modified Ferriman-Gallwey score (mFGS), and adverse events were assessed every 4 weeks for 6 months. The primary endpoint was the percent change in body weight from baseline in both groups. Secondary endpoints included changes in clinical, cardiometabolic, and hormonal parameters and psychosocial features. Thirty-one participants were in the MTF+P group and 30 in the MTF+TPM group. The MTF+TPM group showed greater mean weight loss at 3 months (-3.4% vs. -1.6%, p=0.03) and 6 months (-4.5% vs. -1.4%, p=0.03). Both groups improved androgens, lipids, and psychosocial scores. Participants with ≥3% weight loss at 6 months improved mFGS (8.4 to 6.5, p=0.026). Paresthesia was more common in the MTF+TPM group (23.3% vs. 3.2%, p=0.026). Combining TPM with MTF and a low-calorie diet may be an effective, low-cost, easy-to-use, and safe strategy for weight management in women with PCOS, with mild adverse effects.

Liraglutide for Children 6 to

No medications are currently approved for the treatment of nonmonogenic, nonsyndromic obesity in children younger than 12 years of age. Although the use of liraglutide has been shown to induce weight loss in adults and adolescents with obesity, its safety and efficacy have not been established in children. In this phase 3a trial, which consisted of a 56-week treatment period and a 26-week follow-up period,we randomly assigned children (6 to <12 years of age) with obesity, in a 2:1 ratio, to receive either once-daily subcutaneous liraglutide at a dose of 3.0 mg (or the maximum tolerated dose) or placebo, plus lifestyle interventions. The primary end point was the percentage change in the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters). The confirmatory secondary end points were the percentage change in body weight and a reduction in BMI of at least 5%. A total of 82 participants underwent randomization; 56 were assigned to the liraglutide group and 26 to the placebo group. At week 56, the mean percentage change from baseline in BMI was -5.8% with liraglutide and 1.6% with placebo, representing an estimated difference of -7.4 percentage points (95% confidence interval [CI], -11.6 to -3.2; P<0.001). The mean percentage change in body weight was 1.6% with liraglutide and 10.0% with placebo, representing an estimated difference of -8.4 percentage points (95% CI, -13.4 to -3.3; P = 0.001), and a reduction in BMI of at least 5% occurred in 46% of participants in the liraglutide group and in 9% of participants in the placebo group (adjusted odds ratio, 6.3 [95% CI, 1.4 to 28.8]; P = 0.02). Adverse events occurred in 89% and 88% of participants in the liraglutide and placebo groups, respectively. Gastrointestinal adverse events were more common in the liraglutide group (80% vs. 54%); serious adverse events were reported in 12% and 8% of participants in the liraglutide and placebo groups, respectively. Among children (6 to <12 years of age) with obesity, treatment with liraglutide for 56 weeks plus lifestyle interventions resulted in a greater reduction in BMI than placebo plus lifestyle interventions. (Funded by Novo Nordisk; SCALE Kids ClinicalTrials.gov number, NCT04775082.).

Atrial Fibrillation and Semaglutide Effects in Obesity-Related Heart Failure With Preserved Ejection Fraction: STEP-HFpEF Program

BackgroundObesity is a key factor in the development and progression of both heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF). In the STEP-HFpEF Program (comprising the STEP-HFpEF [Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity] and STEP-HFpEF DM [Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes] trials), once-weekly semaglutide 2.4 mg improved HF-related symptoms, physical limitations, and exercise function and reduced body weight in patients with obesity-related HFpEF. Whether the effects of semaglutide in this patient group differ in participants with and without AF (and across various AF types) has not been fully examined. ObjectivesThe goals of this study were: 1) to evaluate baseline characteristics and clinical features of patients with obesity-related HFpEF with and without a history of AF; and 2) to determine if the efficacy of semaglutide across all key trial outcomes are influenced by baseline history of AF (and AF types) in the STEP-HFpEF Program. MethodsThis was a secondary analysis of pooled data from the STEP-HFpEF and STEP-HFpEF DM trials. Patients with heart failure, left ventricular ejection fraction ≥45%, body mass index ≥30 kg/m2, and Kansas City Cardiomyopathy Questionnaire–Clinical Summary Score (KCCQ-CSS) <90 points were randomized 1:1 to receive once-weekly semaglutide 2.4 mg or matching placebo for 52 weeks. Dual primary endpoints (change in KCCQ-CSS and percent change in body weight), confirmatory secondary endpoints (change in 6-minute walk distance; hierarchical composite endpoint comprising all-cause death, HF events, thresholds of change in KCCQ-CSS, and 6-minute walk distance; and C-reactive protein [CRP]), and exploratory endpoint (change in N-terminal pro–B-type natriuretic peptide [NT-proBNP]) were examined according to investigator-reported history of AF (yes/no). Responder analyses examined the proportions of patients who experienced a ≥5-, ≥10, ≥15, and ≥20-point improvement in KCCQ-CSS per history of AF. ResultsOf the 1,145 participants, 518 (45%) had a history of AF (40% paroxysmal, 24% persistent AF, and 35% permanent AF) and 627 (55%) did not. Participants with (vs without) AF were older, more often male, had higher NT-proBNP levels, included a higher proportion of those with NYHA functional class III symptoms, and used more antithrombotic therapies, beta-blockers, and diuretics. Semaglutide led to larger improvements in KCCQ-CSS (11.5 points [95% CI: 8.3-14.8] vs 4.3 points [95% CI: 1.3-7.2]; P interaction = 0.001) and the hierarchal composite endpoint (win ratio of 2.25 [95% CI: 1.79-2.83] vs 1.30 [95% CI: 1.06-1.59]; P interaction < 0.001) in participants with AF vs without AF, respectively. The proportions of patients receiving semaglutide vs those receiving placebo experiencing ≥5-, ≥10-, ≥15-, and ≥20-point improvement in KCCQ-CSS were also higher in those with (vs without) AF (all P interaction values <0.05). Semaglutide consistently reduced CRP, NT-proBNP, and body weight regardless of AF status (all P interaction values not significant). There were fewer serious adverse events and serious cardiac disorders in participants treated with semaglutide vs placebo irrespective of AF history. ConclusionsIn the STEP-HFpEF Program, AF was observed in nearly one-half of patients with obesity-related HFpEF and was associated with several features of more advanced HF. Treatment with semaglutide led to significant improvements in HF-related symptoms, physical limitations, and exercise function, as well as reductions in weight, CRP, and NT-proBNP in people with and without AF and across AF types. The magnitude of semaglutide-mediated improvements in HF-related symptoms and physical limitations was more pronounced in those with AF vs without AF at baseline. (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])

Creatinine clearance is maintained in a range of wet-bulb globe temperatures and work-rest ratios during simulated occupational heat stress.

We tested the hypothesis that compliance with the National Institute for Occupational Safety and Health (NIOSH) heat stress recommendations will prevent reductions in glomerular filtration rate (GFR) across a range of wet-bulb globe temperatures (WBGTs) and work-rest ratios at a fixed work intensity. We also tested the hypothesis that noncompliance would result in a reduction in GFR compared with a work-rest matched compliant trial. Twelve healthy adults completed five trials (four NIOSH compliant and one noncompliant) that consisted of 4 h of exposure to a range of WBGTs. Subjects walked on a treadmill (heat production: approximately 430 W) and work-rest ratios (work/h: 60, 45, 30, and 15 min) were prescribed as a function of WBGT (24°C, 26.5°C, 28.5°C, 30°C, and 36°C), and subjects drank a sport drink ad libitum. Peak core temperature (TC) and percentage change in body weight (%ΔBW) were measured. Creatinine clearance measured pre- and postexposure provided a primary marker of GFR. Peak TC did not differ among NIOSH-compliant trials (P = 0.065) but differed between compliant versus noncompliant trials (P < 0.001). %ΔBW did not differ among NIOSH-compliant trials (P = 0.131) or between compliant versus noncompliant trials (P = 0.185). Creatinine clearance did not change or differ among compliant trials (P ≥ 0.079). Creatinine clearance did not change or differ between compliant versus noncompliant trials (P ≥ 0.661). Compliance with the NIOSH recommendations maintained GFR. Surprisingly, despite a greater heat strain in a noncompliant trial, GFR was maintained highlighting the potential relative importance of hydration.NEW & NOTEWORTHY We highlight that glomerular filtration rate (GFR) is maintained during simulated occupational heat stress across a range of total work, work-rest ratios, and wet-bulb globe temperatures with ad libitum consumption of an electrolyte and sugar-containing sports drink. Compared with a work-rest matched compliant trial, noncompliance resulted in augmented heat strain but did not induce a reduction in GFR likely due to an increased relative fluid intake and robust fluid conservatory responses.

Acupuncture for obesity：study protocol for a randomised controlled trial

BackgroundObesity is a major public health issue in China and around the world. While acupuncture is often used in clinical practice, there is a lack of conclusive evidence for its...

Efficacy and safety of once-weekly semaglutide 2·4 mg versus placebo in people with obesity and prediabetes (STEP 10): a randomised, double-blind, placebo-controlled, multicentre phase 3 trial

There are currently limited data regarding the effect of semaglutide 2·4 mg in individuals with obesity and prediabetes in clinical trials. We aimed to assess the efficacy and safety of semaglutide 2·4 mg for weight management and glycaemic control in participants with obesity and prediabetes. STEP 10 was a randomised, double-blind, parallel-group, phase 3 trial done across 30 trial sites in Canada, Denmark, Finland, Spain, and the UK and included participants aged 18 years or older with a BMI of 30 kg/m2 or higher and prediabetes according to UK National Institute for Health and Care Excellence criteria (defined as having at least one of the following at screening: HbA1c of 6·0-6·4% [42-47 mmol/mol] or fasting plasma glucose [FPG] of 5·5-6·9 mmol/L). Participants were randomly assigned (2:1) to once-weekly subcutaneous semaglutide 2·4 mg or placebo with diet and physical activity counselling for 52 weeks, followed by a 28-week off-treatment period. Primary endpoints were percentage change in bodyweight and proportion of participants reverting to normoglycaemia (HbA1c <6·0% [<42 mmol/mol] and FPG <5·5 mmol/L) at week 52 (assessed in all randomly assigned participants by intention to treat). Selective safety data were collected for participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT05040971, and is complete. Between Sept 16 and Dec 29, 2021, 138 participants were randomly assigned to semaglutide 2·4 mg and 69 to placebo. 147 (71%) were female and 60 (29%) were male; 183 (88%) were White. All randomly assigned participants received at least one dose of study drug. Baseline mean age was 53 years (SD 11), bodyweight 111·6 kg (22·2), BMI 40·1 kg/m2 (6·9), waist circumference 120·1 cm (14·7), HbA1c 5·9% (0·3; 41·3 mmol/mol [3·0]), and FPG 5·9 mmol/L (0·6). There was a significantly greater reduction in bodyweight with semaglutide 2·4 mg than with placebo at week 52 (-13·9% [SD 0·7] vs -2·7% [0·6]; estimated treatment difference -11·2% [95% CI -13·0 to -9·4]; p<0·0001). Greater proportions of participants reverted to normoglycaemia at week 52 with semaglutide 2·4 mg than with placebo (103 [81%] of 127 vs nine [14%] of 64; odds ratio 19·8 [95% CI 8·7 to 45·2]; p<0·0001). Serious adverse events occurred in 12 (9%) participants receiving semaglutide 2·4 mg versus six (9%) receiving placebo. Adverse events leading to treatment discontinuation occurred in eight (6%) participants in the semaglutide 2·4 mg group versus one (1%) participant in the placebo group. No new safety signals were reported. Semaglutide 2·4 mg provided superior reduction in bodyweight and reversion to normoglycaemia versus placebo in participants with obesity and prediabetes. The safety and tolerability profile was consistent with previous studies and with the GLP-1 receptor agonist class. These findings support the potential use of semaglutide 2·4 mg as a treatment option for individuals with obesity and prediabetes to achieve reversion to normoglycaemia. Novo Nordisk. For the Spanish translation of the abstract see Supplementary Materials section.

Investigation of setmelanotide, an MC4R agonist, for obesity in individuals with Smith-Magenis syndrome

BackgroundSmith Magenis Syndrome (SMS) is a rare genetic disorder caused by RAI1 haploinsufficiency. Obesity in people with SMS is believed partially due to dysfunction of the proximal melanocortin 4 receptor (MC4R) pathway. We therefore studied effects of treatment with the MC4R agonist setmelanotide on obesity and hunger, as well as metabolic, cardiac and safety, in individuals with SMS. MethodsPeople with SMS received once-daily setmelanotide injections, with the dose titrated bi-weekly to a maximum of 3 mg over ∼1 month; and a full-dose treatment duration of 3mo. The primary outcome was percent change in body weight. Secondary outcomes included hunger, waist circumference, body composition, and safety. Results12 individuals, ages 11–39 y, enrolled and 10 completed the full-dose treatment phase. Mean percent change in body weight at end-treatment was − 0.28 % [(95 % CI, −2.1 % to 1.5 %; n = 12; P = 0.66]. Participants experienced a significant decrease in total cholesterol associated with a significant decrease in HDL-cholesterol and a trend for lower LDL-cholesterol. Self-reported hunger was reduced at end-treatment (p = 0.011). All participants reported adverse events (AEs), most commonly injection-site reactions and skin hyperpigmentation. No AEs led to withdrawal or death. ConclusionsIn this trial, setmelanotide did not significantly reduce body weight in participants with SMS. Participants reported significant differences in hunger, but such self-reports are difficult to interpret without a placebo-treated group. The changes in lipid profiles require further investigation. Results of this study do not suggest that dysfunction of the proximal MC4R pathway is the main etiology for obesity in people with SMS.

Exposure to Various Degrees and Durations of Hypobaric Hypoxia Causes a Reduction in Body Weight of Female Adult Rats.

Hypobaric hypoxia refers to a condition where there is a decreased oxygen partial pressure in the air due to low atmospheric pressure. It is known to affect the metabolism, leading to increased basal metabolic rate, alterations in appetite, and changes in cellular metabolism and energy homeostasis. The effects of hypoxia on metabolism and weight loss are influenced by genetic factors, gender, and the duration and severity of exposure to hypoxia. Currently, there are no reports which elucidate the impact of hypobaric hypoxia on female laboratory rats. The aim of this study was to observe the effect of varying degrees and durations of hypobaric hypoxia on the body weight of female rats. In this study, the body weight of 36 laboratory rats divided into six groups was taken at day 0, and then, the rats were exposed to hypobaric hypoxia in a specially designed hypoxia chamber and their body weights were recorded after 5 days and 10 days of hypoxia exposure. The change in body weight at 5 days and 10 days was compared to that of their body weight before the exposure to hypoxia. Data analysis was performed using IBM SPSS version 20. Body weight was reduced in all rats subjected to varying degrees and duration of hypoxia. The percentage change in body weight was higher in moderate and severe hypoxia than in the mild hypoxia group. No significant difference was observed in rats exposed to varying degrees of hypoxia for 5 days as compared to those exposed for 10 days. Hypoxia may cause a reduction in body weight of female rats proportionate to the increasing severity of hypoxia and this reduction remains independent of the duration of exposure to hypoxia.

Efficacy and safety of semaglutide 2.4 mg by race and ethnicity: A post hoc analysis of three randomized controlled trials.

The objective of this study was to evaluate the efficacy and safety of semaglutide 2.4 mg, a glucagon-like peptide-1 receptor agonist, by race and ethnicity, across three phase 3 trials. The Semaglutide Treatment Effect in People with Obesity (STEP) clinical trials evaluated the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg. Here, STEP 1 and 3 data were pooled for analysis; STEP 2 data were examined separately. All analyses were conducted using data from racial and ethnic subgroups. The primary outcome was the estimated treatment difference in percent body weight change for semaglutide 2.4 mg versus placebo. Participants reported race as White (STEP 1 and 3, 75.3%; STEP 2, 59.4%), Black (8.8%; 8.9%), Asian (10.6%; 27.3%), or other racial group (5.3%; 4.4%); and ethnicity as Hispanic or Latino (13.9%; 11.9%) or not Hispanic or Latino (83.9%; 88.1%). There were no significant interactions between treatment effect and race (STEP 1 and 3: p ≥ 0.07; STEP 2: p ≥ 0.15) or ethnicity (p ≥ 0.40; p ≥ 0.85). The safety of semaglutide 2.4 mg was consistent across subgroups. The treatment effect of semaglutide was statistically significant versus placebo and clinically relevant across all racial and ethnic subgroups in STEP 1 and 3 and STEP 2. All subgroups across both samples demonstrated good tolerability.

Efficacy of Semaglutide by Sex in Obesity-Related Heart Failure With Preserved Ejection Fraction: STEP-HFpEF Trials

BackgroundMore women than men have heart failure with preserved ejection fraction (HFpEF). ObjectivesThe purpose of this study was to assess baseline characteristics and treatment effect of semaglutide by sex across the STEP-HFpEF (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity) program. MethodsIn a prespecified secondary analysis of pooled data from STEP-HFpEF and STEP-HFpEF DM (Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes), patients with heart failure (HF), left ventricular ejection fraction ≥45%, body mass index ≥30 kg/m2, and Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) <90 points were randomized 1:1 to once-weekly semaglutide 2.4 mg or matched placebo for 52 weeks. Dual primary endpoints (KCCQ-CSS change and percentage change in body weight) and confirmatory secondary endpoints (6-minute walking distance [6MWD] change; hierarchical composite endpoint comprising all-cause death, HF events, changes in KCCQ-CSS, and 6MWD; and C-reactive protein) were compared between sexes. ResultsOf 1,145 patients, 570 (49.7%) were women. Women had higher body mass index, left ventricular ejection fraction, C-reactive protein, and worse HF symptoms, and were less likely to have atrial fibrillation or coronary artery disease vs men. Semaglutide improved KCCQ-CSS regardless of sex (mean difference in women +7.6 points [95% CI: 4.5-10.7 points]; men +7.5 points [95% CI: 4.3-10.6 points]; P interaction = 0.94) but reduced body weight more in women (mean difference in women −9.6% [95% CI: −10.9% to −8.4%]; men −7.2% [95% CI: −8.4% to −6.0%]; P interaction = 0.006). Semaglutide improved 6MWD (P interaction = 0.21) and the hierarchical composite endpoint (P interaction = 0.66) in both sexes. Fewer serious adverse events were reported with semaglutide vs placebo. ConclusionsIn patients with obesity-related HFpEF, semaglutide 2.4 mg reduced body weight to a greater extent in women, and produced similar improvements in HF-related symptoms, physical limitations, and exercise function, regardless of sex. (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity [STEP-HFpEF]; NCT04788511; and Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes [STEP HFpEF DM]; NCT04916470)

Efficacy and safety of once-weekly tirzepatide for weight management compared to placebo: An updated systematic review and meta-analysis including the latest SURMOUNT-2 trial.

Tirzepatide, a newly developed dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, has received approval for treating type 2 diabetes (T2D) and is currently being studied for its potential in long-term weight control. We aim to explore the safety and efficacy of once-weekly subcutaneous tirzepatide for weight loss in T2D or obese patients. A comprehensive search was performed on various databases including PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov from inception up to April 29, 2024, to identify randomized controlled trials (RCTs) that assessed the efficacy of once-weekly tirzepatide compared to a placebo in adults with or without T2D. The mean difference (MD) and risk ratio (RR) were calculated for continuous and dichotomous outcomes, respectively. The risk of bias was evaluated using the RoB-2 tool (Cochrane), while the statistical analysis was conducted utilizing RevMan 5.4.1 software. Seven RCTs comprising 4795 individuals ranging from 12 to 72 weeks were identified. Compared to the placebo group, tirzepatide at doses of 5, 10, and 15 mg demonstrated significant dose-dependent weight loss. The mean difference (MD) in the percentage change in body weight (BW) was -8.07% (95% CI -11.01, -5.13; p < 0.00001), -10.79% (95% CI -13.86, -7.71; p < 0.00001), and -11.83% (95% CI -14.52, -9.14; p < 0.00001), respectively. Additionally, the MD in the absolute change in BW was -7.5 kg (95% CI -10.9, -4.1; p < 0.0001), -11.0 kg (95% CI -16.9, -5.2; p = 0.0002), and -11.5 kg (95% CI -16.2, -6.7; p < 0.00001), for the 5, 10, and 15 mg doses, respectively. All three doses of tirzepatide also significantly reduced body mass index and waist circumference. Furthermore, it led to a greater percentage of patients experiencing weight loss exceeding 5, 10, 15, 20, and 25%. Moreover, tirzepatide showed great success in reducing blood pressure, blood sugar levels, and lipid profiles. In terms of safety, gastrointestinal side effects were the most frequently reported adverse events in all three doses of tirzepatide groups, which were generally mild-to-moderate and transient. Tirzepatide treatment could lead to remarkable and sustained weight loss that is well-tolerated and safe, representing a novel and valuable therapeutic strategy for long-term weight management.

Tirzepatide for Weight Reduction in Chinese Adults With Obesity

Obesity has become a global public health concern and China has the largest number of affected people worldwide. To assess the efficacy and safety of treatment with tirzepatide for weight reduction in Chinese adults with obesity or overweight and weight-related comorbidities. This randomized, double-blind, placebo-controlled, phase 3 clinical trial conducted at 29 centers in China from September 2021 to December 2022 included Chinese adults (aged ≥18 years) with a body mass index (BMI) greater than or equal to 28 or greater than or equal to 24 and at least 1 weight-related comorbidity, excluding diabetes. Participants were randomly assigned (1:1:1) to receive once-weekly, subcutaneous 10-mg (n = 70) or 15-mg (n = 71) tirzepatide or placebo (n = 69), plus a lifestyle intervention, for 52 weeks. Co-primary end points were the percent change in body weight from baseline and weight reduction of at least 5% at week 52. Efficacy and safety analyses were performed on an intention-to-treat population. Of 210 randomized participants (103 [49.0%] female; mean [SD] age, 36.1 [9.1] years; body weight, 91.8 [16.0] kg; BMI, 32.3 [3.8]), 201 (95.7%) completed the trial. The mean change in body weight at week 52 was -13.6% (95% CI, -15.8% to -11.4%) with tirzepatide 10 mg, -17.5% (95% CI, -19.7% to -15.3%) with tirzepatide 15 mg, and -2.3% with placebo (difference between 10 mg and placebo, -11.3% [95% CI, -14.3% to -8.3%; P < .001]; difference between 15 mg and placebo, -15.1% [95% CI, -18.2% to -12.1%; P < .001]). The percentage of participants achieving body weight reductions of 5% or greater was 87.7% with tirzepatide 10 mg, 85.8% with tirzepatide 15 mg, and 29.3% with placebo (P < .001 for comparisons with placebo). The most frequent treatment-emergent adverse events with tirzepatide were gastrointestinal. Most were mild to moderate in severity, with few events leading to treatment discontinuation (<5%). In Chinese adults with obesity or overweight, once-weekly treatment with tirzepatide 10 mg or 15 mg resulted in statistically significant and clinically meaningful weight reduction with an acceptable safety profile. ClinicalTrials.gov Identifier: NCT05024032.