Percentage Change In Body Weight Research Articles

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.).

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.

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.

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

Obesity 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 HeartFailure and Obesity] and STEP-HFpEF DM [Research Study to Look at How Well Semaglutide Works in People Living With HeartFailure, Obesity and Type 2 Diabetes] trials), once-weekly semaglutide 2.4mg 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. The 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. This 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≥30kg/m2, and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS)<90 points were randomized 1:1 to receive once-weekly semaglutide 2.4mg or matching placebo for 52weeks. 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. Of 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 Pinteraction values not significant). There were fewer serious adverse events and serious cardiac disorders in participants treated with semaglutide vs placebo irrespective of AF history. In 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 HeartFailure and Obesity [STEP-HFpEF; NCT04788511; Research Study to Look at How Well Semaglutide Works in People Living With HeartFailure, Obesity and Type 2 Diabetes [STEP-HFpEF DM; NCT04916470]).

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

Abstract Background: 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. Objective: 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. Materials and Methods: 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. Results: 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. Conclusion: 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

Abstract Aim 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. Methods 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. Results 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 &lt; 0.00001), −10.79% (95% CI −13.86, −7.71; p &lt; 0.00001), and −11.83% (95% CI −14.52, −9.14; p &lt; 0.00001), respectively. Additionally, the MD in the absolute change in BW was −7.5 kg (95% CI −10.9, −4.1; p &lt; 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 &lt; 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. Conclusion 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.

Safety and efficacy of GLP-1 and glucagon receptor dual agonist for the treatment of type 2 diabetes and obesity: a systematic review and meta-analysis of randomized controlled trials.

This study aimed to investigate the effects of randomized, placebo-controlled trials involving the GLP-1 and glucagon receptor dual agonists, mazdutide, and cotadutide, on glycaemic control and body weight changes in individuals with type 2 diabetes mellitus (T2DM), obesity, or both. We conducted searches in Medline, PubMed, Scopus, the Cochrane database, and Web of Science up to March 5, 2024. The primary outcomes assessed were changes in HbA1c level and percentage changes in body weight from baseline (CFB). Eleven studies and four unpublished trials were included. The pooled meta-analysis revealed a significant reduction in HbA1c (MD = -0.63%; 95% CI = [-0.82, -0.44]; P < 0.00001), fasting plasma glucose (MD = -1.71 mmol/L; 95% CI = [-2.31, -1.10]; P < 0.00001), and percentage change in body weight (MD = -4.16%; 95% CI = [-5.41, -2.92]; P < 0.00001). Safety analysis revealed no significant change in serious adverse events (OR = 1.03; 95% CI = [0.61, 1.75]; P = 0.91), but there were significantly higher odds of treatment-emergent adverse events (OR = 2.52; 95% CI = [1.92, 3.30]; P < 0.00001) and vomiting (OR = 6.05; 95% CI = [3.52, 10.40]; P < 0.00001). These results suggest that mazdutide and cotadutide are effective for glycaemic control and weight reduction in individuals with T2DM, obesity, or both.

243 Effects of body weight change in pre-production Duroc boars on semen collection training, semen production parameters, and longevity in a commercial boar stud

Abstract Our objective was to assess the effects of percentage body weight (BW) change in developing Duroc boars on semen collection training, semen production parameters, and longevity in a commercial boar stud. Retrospectively, 164 boars were divided into one of three groups based on their percentage BW change from arrival to the boar stud until the end of the 42-d isolation period. The one-third of boars that had the greatest percentage of BW change during the isolation period gained 36.1% to 10.1% (TOP). The middle one-third of boars that were intermediate in percentage BW change during isolation gained 9.7% to 2.6% (MIDDLE). The final group consisted of one-third of boars that either minimally gained or lost BW (2.5% to -9.5% change in BW; BOTTOM). During the isolation period boars in the TOP group lost the least amount of backfat (indicated by ultrasound or caliper score; P &amp;lt; 0.05), while boars in the BOTTOM group lost the most backfat. Average boar age at the time of successfully becoming a working boar (successfully mounting the collection dummy and producing an ejaculate with a motility ≥ 70% and percent normal morphology ≥ 65%) and the proportion of boars that were successful at become working boars did not differ between groups (P &amp;gt; 0.05). Among working boars, the concentration of sperm in ejaculates tended to differ (P = 0.0740) between groups (Table). Boars in the TOP group had a greater percentage of sperm with normal morphology (P = 0.0337) than boars in the BOTTOM group. There was a group by production week interaction (P &amp;lt; 0.0001) for semen ejaculate volume, total number of sperm, and total number of sperm with normal morphology. Boars in the TOP and MIDDLE groups produced more total sperm and normal sperm than the BOTTOM group from wk 8 to 20 of being working boars, resulting in production of considerably more doses for artificial insemination. During their time as working boars, removal from the stud by cull or death was not different between groups (P &amp;gt;0.05). There was also no difference (P &amp;gt; 0.05) between groups on the average week of removal from the stud, with each group having boars most frequently removed at wk 22 of production. While percentage BW change during isolation did not affect semen collection training and longevity in the stud, the increase in production of total normal sperm in the TOP and MIDDLE groups compared with the BOTTOM group could have substantial economic benefits for boar stud. Our study suggests that managing boars individually to ensure they stay in a positive metabolic state is ideal for optimal semen production at a boar stud.

Alternative models to support weight loss in chronic musculoskeletal conditions: effectiveness of a physiotherapist-delivered intensive diet programme for knee osteoarthritis, the POWER randomised controlled trial

ObjectivesTo determine if physiotherapists can deliver a clinically effective very low energy diet (VLED) supplementary to exercise in people with knee osteoarthritis (OA) and overweight or obesity.Methods88 participants with knee...

Ad Libitum Drinking Does Not Modify Renal Oxidative Stress or Inflammation During Simulated Occupational Heat Stress

Prolonged heat exposure increases acute kidney injury (AKI) risk likely due to renal oxidative stress and inflammation. However, the effect of occupational heat stress (OHS) and the modifying role of hydration on renal oxidative stress and inflammation is unknown. This study tested the hypothesis that compared to fluid restriction ad libitum drinking consistent with OHS recommendations will attenuate renal oxidative stress and inflammation during simulated OHS. In a randomized, crossover design, 13 healthy adults (5 women) completed two 2 h OHS simulations consisting of of 8 circuits of treadmill walking (10 min) and rowing (5 min) at an oxygen uptake of 1.2 L/min in a wet bulb globe temperature of 33.1±0.2°C. In the drinking trial (Drink), subjects were provided 237 mL of a non-caloric sport drink (Gatorade Zero) every 15 min and drank ad libitum. In the fluid restriction trial (NoDrink), no fluid was provided. Rectal temperature and body weight were recorded. Urine and blood samples were collected pre-, post- and 1 h post- exposure. Inflammatory (monocyte chemotactic protein-1, MCP-1) and oxidative stress (thioredoxin 1, TRX-1) markers were measured in urine and serum, and fractional excretion (FE) was calculated. AKI risk was quantified as the product of urine insulin-like growth factor-binding protein 7 and urine tissue inhibitor of metalloproteinase 2 ([IGFBP7•TIMP-2]). Data are presented as mean ± SD. Peak rectal temperature was not different between trials (Drink: 38.5±0.4°C, NoDrink: 38.6±0.4°C, p=0.346). Percent changes in body weight were lower in Drink (1.3±0.8% vs. 2.8±0.9%, p&lt;0.001). FETRX-1 was elevated at post- (0.50±0.00%) compared to pre- (0.36±0.00%, p=0.011) and 1 h post- (0.29±0.13%, p=0.011). FEMCP-1 was elevated at post- (1.25±0.18%) compared to pre- (1.02±0.17%, p=0.006) but not 1 h post- (1.27±0.03%, p&gt;0.999). FETRX-1 and FEMCP-1 did not change significantly between trials (trial x time: p³0.622). [IGFBP7•TIMP-2] was higher at 1 h post- (17.5±1.0 (ng/mL)2/1000) compared to pre- (0.2±0.1 (ng/mL)2/1000, p&lt;0.001) and post- (1.1±0.4 (ng/mL)2/1000, p&lt;0.001) but did not differ between trials (trial x time: p=0.556). Peak changes in [IGFBP7•TIMP-2] were not significantly correlated with peak changes in FETRX-1 (r=0.126, p=0.557) or FEMCP-1 (r=0.292, p=0.166) and were correlated with peak changes in serum MCP-1 (r=0.714, p&lt;0.001) but not serum TRX-1 (r=0.227, p=0.286). Two hours of simulated OHS increased renal inflammation (FEMCP-1), oxidative stress (FETRX-1), and AKI risk ([IGFBP7•TIMP-2]), while ad libitum drinking did not modify FEMCP-1, FETRX-1, or [IGFBP7•TIMP-2]. Lack of correlations between peak changes in [IGFBP7•TIMP-2] and FEMCP-1, FETRX-1, or serum TRX-1, but the strong positive correlation with peak serum MCP-1 suggests a role for systemic inflammation in OHS induced AKI risk. NCT05458843 Funding: R01OH011528. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Body weight loss is a simple and useful indicator of prognosis and predictive tolerability in the first year of nintedanib therapy in patients with interstitial lung disease

BackgroundNintedanib is generally safe and well tolerated and can improve prognosis in patients with various interstitial lung diseases (ILDs). Appropriate management of adverse events of nintedanib is important to ensure its long-term persistent use. Weight loss is a routinely assessed adverse event in clinical practice. This study aimed to elucidate whether body weight change in the first year of nintedanib therapy can indicate prognosis and predict tolerability in patients with ILD. MethodsWe analysed 245 consecutive ILD patients treated with nintedanib. We calculated the slope of body weight change using baseline weight and that recorded closest after the first year and then categorized percent change in body weight at this time. Significant weight loss was defined as that ≥5%. ResultsSubjects included 67 patients with idiopathic pulmonary fibrosis (IPF) and 76 with non-IPF progressive fibrosing-ILD including fibrotic hypersensitivity pneumonitis (n = 16), unclassifiable (n = 35), connective tissue disease-ILD (n = 21), and nonspecific interstitial pneumonia (n = 4). Older age, low body weight at initial examination, significant weight loss, and lower %FVC were significant predictors of discontinuation of nintedanib. Patients with weight loss ≥5% over the first year showed worse survival than those with weight loss <5% regardless of whether IPF existed or BMI indicated obesity. ConclusionsCareful monitoring of body weight change might suggest useful information for predicting long-term use of nintedanib and mortality risk in ILD patients treated with nintedanib. Appropriate body weight management is needed to prevent adverse events of nintedanib itself.

Oxidative Stress Markers Evaluation after Prolonged Administration of Aqueous Extract of Raphia Hookeri Fruit Pulp in Male Wistar Rats

The study investigated effect of prolonged administration of Raphia Hookeri fruit pulp on oxidative stress markers in male wistar rats. A total of 24 male wistar rats of weight ranging from 200g to 350g were used. The rats divided in 4 groups, 3 groups administered orally with doses of extract at 500mg/kg, 1000mg/kg and 2000mg/kg body weight while control group fed with feed and water for 28 days. The animals sacrificed, samples taken, laboratory test done for stress markers. Statistical analysis done at p&lt;0.05, values expressed as SEM. Results showed Malondialdehyde (MDA) values for group 2(0.77 ± 0.32nm/ml), group 3(1.79 ± 0.73nm/ml) and group 4(3.35 ± 0.20nm/ml) while for group 1(Control group) MDA value is 4.10 ± 0.3nm/ml. Mean values for Superoxide Dismutase (SOD) in treated groups (2-4) were 18.00 ± 1.0 units/ml, 29.50 ± 8.50units/ml, and 33.50 ± 37.25units/ml respectively and mean value for control group was 68.00 ± 4.0units/ml. Mean values for Glutathione Peroxidase (GPx) in test groups (2-4) were 53.50 ± 10.50ng/ml, 63.50 ± 5.50ng/ml, and 82.50 ± 6.50ng/ml respectively. GPx value for control group was 94.00 ± 3.00ng/ml. There was a graded increase from low dose to high dose. All treated groups indicated marginally (P&gt;0.05) reduced values of Percentage change in body weight when compared to the control group (Group 1). Elevated levels of MDA indicates an increased oxidative stress and lipid. Higher levels of SOD and Gpx. This research demonstrates the ability of Raphia Hookeri fruit pulp to decrease oxidative stress hence regular consumption is recommended.

Orforglipron, a novel non-peptide oral daily glucagon-like peptide-1 receptor agonist as an anti-obesity medicine: A systematic review and meta-analysis.

Orforglipron is a novel once-daily oral non-peptide glucagon-like peptide-1 receptor agonist with several recently published randomized controlled trials (RCTs) evaluating its role in diabetes and obesity. No meta-analysis has analyzed the efficacy and safety of orforglipron; this meta-analysis aimed to address this knowledge gap. A systematic search was conducted in electronic databases to identify RCTs that included individuals with obesity who were administered orforglipron and compared to either a placebo or an active comparator. The primary outcome of interest was the percent change in body weight. From 12 initially screened articles, data from three RCTs involving 774 people were analyzed with a follow-up duration of up to 36weeks. Compared to placebo, patients receiving orforglipron 12mg/day (mean difference (MD), MD -5.48%, 95% CI [-7.64, -3.33], p<0.01), 24mg/day (MD -8.51%, 95% confidence interval (CI) [-9.88, -7.14], p<0.01), 36mg/day (MD -8.84%, 95% CI [-11.68, -6.00], p<0.01) and 45mg/day (MD -8.24%, 95% CI [-12.84, -3.63], p<0.01) had a significantly greater percent reduction in body weight. The percentage of patients being able to achieve >15% weight loss from baseline was significantly higher with orforglipron 24mg/day [Odds ratio (OR) 21.90 (95% CI [4.06, 118.15], p=0.0003), 36mg/day (OR 17.43, 95% CI [3.18, 95.66], p=0.001) and 45mg/day (OR 23.17, 95% CI [4.37, 123.03], p=0.0002). Total but not severe adverse events were significantly higher with all the doses of orforglipron compared to placebo, with the hazard ratios being higher with higher doses. Gastrointestinal side-effects were predominant side effects, being dose-dependent, with nausea, vomiting, constipation, and gastroesophageal reflux being the predominant ones. Orforglipron at 24-45mg/day doses is an effective weight loss medication. The efficacy versus side effect profile suggests that 24-36mg/day is the most optimal dose for orforglipron as an anti-obesity medicine.