Percentage Change In Body Weight Research Articles

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 Eleven studies and four unpublished trials were included.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.

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.

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...

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.

Efficacy and Safety of Tirzepatide in Adults With Type 1 Diabetes: A Proof of Concept Observational Study.

Tirzepatide is approved by the United States Food and Drug Administration (FDA) for the management of type 2 diabetes. The efficacy and safety of this drug have not been studied in people with type 1 diabetes (T1D). In this single-center, retrospective, observational study, hemoglobin A1C (HbA1c), weight, body mass index (BMI), and continuous glucose monitoring (CGM) data were collected from electronic health records of adults with T1D at initiation of tirzepatide and at subsequent clinic visits over 8 months. Primary outcomes were reduction in HbA1c and percent change in body weight and secondary outcomes were change in CGM metrics and BMI over 8 months from baseline. The mean (±SD) age of the 26 adults (54% female) with T1D was 42 ± 8 years with a mean BMI of 36.7 ± 5.3 kg/m2. There was significant reduction in HbA1c by 0.45% at 3 months and 0.59% at 8 months, and a significant reduction in body weight by 3.4%, 10.5%, and 10.1% at 3, 6, and 8 months after starting tirzepatide. Time in target range (TIR = 70-180 mg/dL) and time in tight target range (TITR = 70-140 mg/dL) increased (+12.6%, P = .002; +10.7%, P = .0016, respectively) and time above range (TAR >180 mg/dL) decreased (-12.6%, P = .002) at 3 months, and these changes were sustained over 8 months. The drug was relatively safe and well tolerated with only 2 patients discontinuing the medication. Tirzepatide significantly reduced HbA1c and body weight in adults with T1D. A randomized controlled trial is needed to establish efficacy and safety of this drug in T1D.

Efficacy and safety of tirzepatide in people with type 2 diabetes by baseline body mass index: An exploratory subgroup analysis of SURPASS-AP-Combo.

To assess the efficacy and safety of tirzepatide versus insulin glargine in people with type 2 diabetes (T2D) by baseline body mass index (BMI). Participants with T2D from the Phase 3 SURPASS-AP-Combo trial (NCT04093752) were categorized into three BMI subgroups (normal weight [<25 kg/m2 ], overweight [≥25 and <30 kg/m2 ], and obese [≥30 kg/m2 ]) according to World Health Organization criteria. Exploratory outcomes including glycaemic control, body weight, cardiometabolic risk, and safety were compared among three tirzepatide doses (5, 10 or 15 mg) and insulin glargine. Of 907 participants, 235 (25.9%) had a BMI <25 kg/m2 , 458 (50.5%) a BMI ≥25 to <30 kg/m2 , and 214 (23.6%) a BMI ≥30 kg/m2 at baseline. At Week 40, all tirzepatide doses led to a greater reduction in mean glycated haemoglobin (HbA1c; -2.0% to -2.8% vs. -0.8% to -1.0%, respectively) and percent change in body weight (-5.5% to -10.8% vs. 1.0% to 2.5%, respectively) versus insulin glargine, across the BMI subgroups. Compared with insulin glargine, a higher proportion of tirzepatide-treated participants achieved treatment goals for HbA1c and body weight reduction. Improvements in other cardiometabolic indicators were also observed with tirzepatide across all the BMI subgroups. The safety profile of tirzepatide was similar across all subgroups by BMI. The most frequent adverse events with tirzepatide were gastrointestinal-related events and decreased appetite, with relatively few events leading to treatment discontinuation. In participants with T2D, regardless of baseline BMI, treatment with tirzepatide resulted in statistically significant and clinically meaningful glycaemic reductions and body weight reductions compared with insulin glargine, with a safety profile consistent with previous reports.

Semaglutide 2.4 mg clinical outcomes in patients with obesity or overweight in a real‐world setting: A 6‐month retrospective study in the United States (SCOPE)

AbstractBackgroundManagement guidelines for obesity suggest maintaining a minimum of 5% body weight reduction to help prevent or lower the risk of developing conditions such as hypertension and type 2 diabetes. However, achieving long‐term weight control is difficult with lifestyle modification alone, making it essential to combine pharmacotherapy with diet and exercise in individual cases. Semaglutide 2.4 mg has demonstrated significant reductions in body weight and cardiometabolic risk factors in clinical trials, but information on outcomes in a real‐world setting is limited.ObjectiveTo assess changes in body weight and other clinical outcomes at 6‐month follow‐up among adults on semaglutide 2.4 mg in a real‐world setting in the United States (US).MethodsObservational and retrospective cohort study of patients initiating treatment between 15 June 2021, and 31 March 2022, using a large US claims‐linked electronic health record database.ResultsMean (±SD) body mass index (BMI) of the 343 patients included in the analysis was 37.9 ± 5.5 kg/m2. After 6 months, mean body weight change was −10.5 ± 6.8 kg (95% CI: −11.2; −9.8, p &lt; 0.001) and mean percentage body weight change was −10.0% ± 6.6% (95% CI: −10.7; −9.3, p &lt; 0.001). Most (79.0%) patients had ≥5% body weight reduction, 48.1% had ≥10% body weight reduction, and 19.0% had ≥15% body weight reduction. Among patients with available data, the mean change in HbA1c (n = 30) was −0.6% ± 1.2% (95% CI: −1.0; −0.1, p = 0.016) and nearly two‐thirds of patients with prediabetes or diabetes at baseline reverted to normoglycemia. Mean reductions of −4.4 ± 12.3 mmHg (95% CI: −5.7; −3.0, p &lt; 0.001) and −1.7 ± 8.4 mmHg (95% CI: −2.6; −0.7, p &lt; 0.001) were observed in systolic and diastolic blood pressure, respectively (n = 307). Statistically significant reductions in mean total cholesterol (−12.2 ± 38.8 mg/dl [95% CI: −24.3 to −0.06, p &lt; 0.049]) and triglycerides (−18.3 ± 43.6 mg/dl [95% CI: −4.7; −31.9, p &lt; 0.009]) were also observed (n = 42).ConclusionsThis study demonstrated the effectiveness of semaglutide 2.4 mg in reducing body weight and improving cardiometabolic parameters in adults with overweight or obesity in a real‐world clinical practice setting, showing a significant mean body weight reduction and improvements in biomarkers like blood pressure and HbA1c over a 6‐month period. These findings, aligning with previous clinical trials at comparable time points, highlight the clinical relevance of semaglutide as an effective therapeutic option for obesity.

Effects of gamal leaf extract (Gliricidia sepium Jacq.) on body weight and internal organ performance of mice (Mus musculus L.)

Gamal leaves (Gliricidia sepium Jacq.) contain toxic compounds that have the potential to act as vegetable rodenticides, such as alkaloids, tannins, dicumerol, and hydrogen cyanic acid (HCN). Coumarin compounds can bind vitamin K, disrupt the circulatory system, and damage liver cells. The compounds dicumerol and warfarin are used as rat poison because of their anticoagulant properties, which prevent blood clots in the heart. Alkaloid and tannin compounds can damage liver cells through liver necrosis and bleeding in the digestive system. This study aims to determine the effect of Gamal leaf extract on body weight and internal organ performance in mice (Mus musculus L.). The experimental research method is based on a Completely Randomized Design (CRD) pattern. A total of 16 mice weighing 20-22 grams consisting of 4 treatments, namely A0 (water control), A1 (extract 10 mg/g BW), A2 (extract 15 mg/g BW) and A3 (extract 20 mg/g BW). The extract was given orally for 14 days, and body weight was measured every 3 days to obtain data on changes in body weight (PBB). At the end of the treatment, the mice were sacrificed using chloroform and then dissected to observe the performance of the liver, kidney and heart organs in color appearance and organ weight. Quantitative data were analyzed using one-way ANOVA and further DMRT test α=0.05. The research showed that mice's mean change in body weight (PBB) decreased significantly as the dose of Gamal leaf extract increased. The percentage of liver organ weight (BOH), kidney organ weight (BOG), and heart organ weight (BOJ) decreased as the dose of Gamal leaf extract increased. The research results concluded that Gamal leaf extract caused color changes in the internal organs of mice and significantly affected the percentage change in body weight (PBB) and internal organ weight (BOD) of mice along with increasing doses of Gamal leaf extract.

1985. A Prospective, Randomized Trial to Assess a Protease Inhibitor–based Regimen Switch Strategy to Manage Integrase Inhibitor–related Weight Gain

Abstract Background Integrase inhibitor (INI)–based antiretroviral (ARV) therapies are associated with greater weight gain than non-nucleoside reverse transcriptase inhibitor– or boosted protease inhibitor–based regimens, disproportionately affecting Black and Hispanic individuals and women. The mechanisms underlying this weight gain are unknown, and there are no prospective, randomized data exploring the impact of switching ARV classes to mitigate or reverse ARV-related weight gain. Methods DEFINE (ClinicalTrials.gov: NCT04442737) is a randomized (1:1), prospective, 48-week, active-controlled, open-label, multicenter phase 4 study evaluating switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) versus continuing INI+TAF/emtricitabine (FTC) in virologically-suppressed HIV-1–infected adults who had ≥10% weight gain while on the INI-based regimen. The primary objective was to assess percent change in body weight from baseline to Week 24 in both arms. The primary endpoint was analyzed using a mixed model for repeated measures in the intent-to-treat set of randomized participants who had received ≥1 dose of study drug. Secondary endpoints included change in body mass index (BMI), waist circumference (WC), efficacy, and safety. Data through Week 24 are reported. Results Overall, 103 adults were randomized to D/C/F/TAF (n=53) or continued INI+TAF/FTC (n=50); 30% were female and 61% were Black/African American, with median 27.0 months virologic suppression on INI+TAF/FTC (Table 1). Discontinuation rates were low and similar between arms. At Week 24, there was no significant difference in percent change in body weight from baseline between the D/C/F/TAF and INI+TAF/FTC arms (Figure). Most participants in each arm had body weight changes of ≤±3% and remained within baseline BMI and WC categories. Percent body weight changes for key subgroups are shown in Table 2. Switching to D/C/F/TAF was safe and well tolerated, and efficacy was maintained.Table 1.Demographics and Baseline Characteristics (ITT Set)BMI, body mass index; D/C/F/TAF, darunavir/cobicistat/emtricitabine/tenofovir alafenamide; FTC, emtricitabine; INI, integrase inhibitor; ITT, intent-to-treat; TAF, tenofovir alafenamide. *One participant in the D/C/F/TAF arm did not have available data. Percent Change From Baseline in Body Weight Over Time for Participants Who Switched to D/C/F/TAF and Those Who Continued Their Current INI+TAF/FTC Regimen (ITT Set) D/C/F/TAF, darunavir/cobicistat/emtricitabine/tenofovir alafenamide; FTC, emtricitabine; INI, integrase inhibitor; ITT, intent-to-treat; LS, least-squares; TAF, tenofovir alafenamide. LS means percent changes in body weight were calculated in the ITT set of randomized participants who had received ≥1 dose of study drug using a mixed model for repeated measures, in which the dependent variable was percent change from baseline in body weight; independent variables were treatment, baseline body mass index, sex, and race (Black/African American vs non–Black/African American); and visits were repeated measures. Participants in the ITT set with baseline records and ≥1 postbaseline record were included. Conclusion There was no significant difference in weight change through 24 weeks after switching from an INI-based regimen to D/C/F/TAF in adults with INI-related weight gain. Additional analyses are ongoing, including follow up through Week 48 and evaluation of changes in biomarkers and body composition (DEXA).Table 2.Percent Change From Baseline in Body Weight at Week 24 Among Key Subgroups (ITT Set)BMI, body mass index; D/C/F/TAF, darunavir/cobicistat/emtricitabine/tenofovir alafenamide; FTC, emtricitabine; INI, integrase inhibitor; ITT, intent-to-treat; TAF, tenofovir alafenamide. Disclosures William R. Short, MD, Gilead Sciences: Advisor/Consultant|ViiV: Advisor/Consultant|ViiV: Honoraria Moti Ramgopal, MD, FACP, FIDSA, AbbVie: Honoraria|Gilead Sciences, Inc.: Advisor/Consultant|Gilead Sciences, Inc.: Honoraria|Janssen Pharmaceuticals: Advisor/Consultant|Janssen Pharmaceuticals: Honoraria|Merck: Advisor/Consultant|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Honoraria Debbie P. Hagins, MD, FAPCR, AAHIVS, Janssen Pharmaceuticals: Advisor/Consultant Johnnie Lee, MD, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds Richard Bruce Simonson, BS, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds Tien-Huei Hsu, PhD, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds Ping Xu, PhD, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds David Anderson, MD, Janssen Pharmaceuticals: Employee|Janssen Pharmaceuticals: Stocks/Bonds

376 Effects of Mineral Supplementation During Range Grazing on Ovine Performance

Abstract Western US sheep production systems are dependent on rangeland forages to meet nutritional needs for animal production. While many native rangeland soils and forages are deficient in minerals like Cu, Se, and Zn, it is unknown whether ewes will alter forage selection if they receive a mineral supplemented diet and if alternative forages will affect performance on range. The objectives of this study are to quantify the effects of mineral supplementation on ewe forage selectivity on rangeland, range utilization, and animal performance. We hypothesized ewes who receive a trace mineral supplement will have a more diverse diet, greater rangeland utilization, and improved performance characteristics than their non-supplemented contemporaries. In this study, (n = 59) ewes were grazed across four summer pastures on Cedar Mountain near Cedar City, Utah. Ewes between the ages of 1 and 6 with an average weight of 87 Kg ± 13 Kg were stratified by initial weight and breed into one of two different treatment groups: 1) trace mineral supplement ad libitum (TRT; n = 30), or 2) no mineral supplement (CON; n = 29). Ewe breed types consisted of black face type breeds (BLF; Suffolk) and white face type breeds (WF; Targhee, Rambouillet, and their crosses). All ewes received a similar diet of alfalfa hay and triticale without access to ad libitum mineral supplementation 30 days before the start of the trial. A solar powered C-lock inc. pro was used to track individual animal mineral intake. Back fat (BF) and loin eye depth (LED) were measured at day 0 and day 116 of the trial via ultrasound. Additionally, fecal samples were collected and used for fecal metabarcoding (fDNA) at approximately 30% pasture utilization, which measures the proportion of plant DNA in the feces to determine forage species consumed. Plant species were sorted into functional groups (forbs, grass likes, grasses, shrubs, and trees). The GLM procedure of SAS was used to analyze BF, LED, and fDNA. The mixed procedure of SAS with day as a repeated measure was used to analyze percentage change in body weight. Control ewes had greater BF by 0.08 cm (P = 0.02). No difference in BF was observed by breed (P = 0.8). Loin eye depth was greater by 0.2 cm (P = 0.01) in BLF ewes than WF ewes. Supplemented ewes maintained 1% more of their initial body weight than CON ewes (P = 0.01). No forage selection differences were observed by treatment or breed (P&amp;gt; 0.2). The current study results indicate that mineral supplementation on range may not affect forage selectivity but can benefit animals by maintaining body weight over the grazing season.

SAT656 Weight Reduction After 6 Months Of Setmelanotide Treatment In Patients With Hypothalamic Obesity

Abstract Disclosure: C.L. Roth: Other; Self; Received research support from Rhythm Pharmaceuticals, Inc. A.H. Shoemaker: Advisory Board Member; Self; Received payments from Rhythm Pharmaceuticals, Inc and Saniona for advisory boards and lectures. Other; Self; Received research support from Rhythm Pharmaceuticals, Inc. M. Gottschalk: Advisory Board Member; Self; Received compensation for consulting and participation on advisory boards from Rhythm Pharmaceuticals, Inc. Other; Self; Received funding for clinical trials from Rhythm Pharmaceuticals, Inc. J. Miller: Other; Self; Received research support from Harmony Biosciences, Rhythm Pharmaceuticals, Inc, Soleno Therapeutics, and Tryp Therapeutics. G. Yuan: Employee; Self; Employee of Rhythm Pharmaceuticals, Inc. Stock Owner; Self; Has company-awarded RSU and options. S. Malhotra: Employee; Self; Employee of Rhythm Pharmaceuticals, Inc. Stock Owner; Self; Stockholder in in Rhythm Pharmaceuticals, Inc. C. Scimia: Employee; Self; Employee of Rhythm Pharmaceuticals, Inc. Stock Owner; Self; Has company-awarded RSU and options. M. Abuzzahab: Advisory Board Member; Self; Received compensation for advisory board participation from Consynance, Endo Pharmaceutical, Pfizer, and Rhythm Pharmaceuticals, Inc. Consulting Fee; Self; Received compensation for consulting from Consynance, Endo Pharmaceutical, Pfizer, and Rhythm Pharmaceuticals, Inc. Speaker; Self; Received compensation for speaking engagements from Consynance, Endo Pharmaceutical, Pfizer, and Rhythm Pharmaceuticals, Inc. Other; Self; Received research support from Ascendis, Levo Pharmaceuticals, Lumos, NovoNordisk, Rhythm Pharmaceuticals, Inc, Saniona, and Soleno. Background: Hypothalamic obesity (HO) is an acquired form of severe obesity characterized by rapid and excessive weight gain resulting from insult to the hypothalamus—primarily caused by tumor invasion, resection, or radiotherapy—that can impair melanocortin-4 receptor (MC4R) pathway signaling. Treatment with setmelanotide, an MC4R agonist, resulted in weight loss and hunger reduction at 16 weeks in a Phase 2 trial of patients with HO. Here, we report changes in age-appropriate weight-related parameters after 6 months of treatment with setmelanotide in patients with HO who entered a long-term extension (LTE) trial. Methods: A Phase 2, multicenter, open-label study (NCT04725240) examined the efficacy and safety of 16-week setmelanotide treatment in patients aged ≥6 to ≤40 years with a clinical diagnosis of HO. Patients who met the primary endpoint of ≥5% body mass index (BMI) reduction from baseline at Week 16 or experienced investigator-determined clinically meaningful benefit and demonstrated adequate safety were eligible to enroll in the LTE trial (NCT03651765). We assessed the proportion of patients who achieved ≥10% BMI reduction as well as changes in age-appropriate weight-related parameters (ie, mean percent change in body weight for adults [aged ≥18 years] and mean change in BMI Z score and percent of the 95th BMI percentile [%BMI95] for children [aged &amp;lt;18 years]) from index trial baseline to Month 6 of setmelanotide treatment. Results: Of 18 patients originally enrolled in the index trial, 14 (77.8%) continued into the LTE and 13 (72.2%) had received ≥6 months of setmelanotide treatment at the time of this analysis. HO was diagnosed in these patients secondary to treatment of craniopharyngioma (n=11), hypothalamic hamartoma (n=1), and juvenile pilocytic astrocytoma (n=1). At Month 6, 11 of 13 patients (84.6% [90% confidence interval, 59.0%–97.2%) achieved ≥10% BMI reduction from index trial baseline; the remaining 2 patients achieved ≥5% reduction from baseline at Month 6. In adults (n=2), the mean (standard deviation [SD]) percent change in body weight from baseline to Month 6 was −16.2% (7.2%). In children (n=11), the mean (SD) change from baseline in BMI Z score was −1.7 (1.1) and in %BMI95 was −34.8 (14.9) percentage points at Month 6. The most frequent adverse events were nausea (n=9 [69.2%]), skin hyperpigmentation (n=5 [38.5%]), and vomiting (n=4 [30.8%]). Four serious adverse events were reported in 2 patients (Clostridium difficile colitis in 1 patient; malaise, septic shock, and influenza in 1 patient) and were determined not related or unlikely related to study drug. Conclusions: In a heterogeneous population of patients with HO secondary to treatment of hypothalamic tumors, 6 months of setmelanotide treatment was associated with sustained meaningful improvements in weight and BMI with no new safety signals. Presentation: Saturday, June 17, 2023

Safety and Efficacy of Liraglutide, 3.0 mg, Once Daily vs Placebo in Patients With Poor Weight Loss Following Metabolic Surgery

Metabolic surgery leads to weight loss and improved health, but these outcomes are highly variable. Poor weight loss is associated with lower circulating levels of glucagon-like peptide-1 (GLP-1). To assess the efficacy and safety of the GLP-1 receptor agonist, liraglutide, 3.0 mg, on percentage body weight reduction in patients with poor weight loss and suboptimal GLP-1 response after metabolic surgery. The Evaluation of Liraglutide 3.0 mg in Patients With Poor Weight Loss and a Suboptimal Glucagon-Like Peptide-1 Response (BARI-OPTIMISE) randomized placebo-controlled trial recruited adult patients at least 1 year after metabolic surgery who had experienced 20% or less body weight loss from the day of surgery and a suboptimal nutrient-stimulated GLP-1 response from 2 hospitals in London, United Kingdom, between October 2018 and November 2019. Key exclusion criteria were type 1 diabetes; severe concomitant psychiatric, gastrointestinal, cardiac, kidney or metabolic disease; and use of insulin, GLP-1 receptor analogues, and medication that can affect weight. The study period was 24 weeks followed by a 4-week follow-up period. Last participant follow-up was completed in June 2020. All participants and clinical study personnel were blinded to treatment allocation. Of 154 assessed for eligibility, 70 met trial criteria and were included in the study, and 57 completed follow-up. Liraglutide, 3.0 mg, once daily or placebo as an adjunct to lifestyle intervention with a 500-kcal daily energy deficit for 24 weeks, on a 1:1 allocation by computer-generated randomization sequence, stratified by surgery type (Roux-en-Y gastric bypass [RYGB] or sleeve gastrectomy [SG]) and type 2 diabetes status. The primary outcome was change in percentage body weight from baseline to the end of the 24-week study period based on an intention-to-treat analysis. Participant safety was assessed through monitoring of biochemical parameters, including kidney and liver function, physical examination, and assessment for adverse events. A total of 70 participants (mean [SD] age, 47.6 [10.7] years; 52 [74%] female) with a poor weight loss response following RYGB or SG were randomized to receive 3.0-mg liraglutide (n = 35) or placebo (n = 35). All participants received at least 1 dose of the trial drug. Eight participants discontinued treatment (4 per group), and 2 in the 3.0-mg liraglutide group and 1 in the placebo group were lost to follow-up. Due to COVID-19 restrictions, 3 participants in the 3.0-mg liraglutide group and 7 in the placebo group were unable to attend their final in-person assessment. Estimated change in mean (SD) percentage body weight from baseline to week 24 was -8.82 (4.94) with liraglutide, 3.0 mg (n = 31), vs -0.54 (3.32) with placebo (n = 26). The mean difference in percentage body weight change for liraglutide, 3.0 mg, vs placebo was -8.03 (95% CI, -10.39 to -5.66; P < .001). Adverse events, predominantly gastrointestinal, were more frequent with liraglutide, 3.0 mg (28 events [80%]), than placebo (20 events [57%]). There were no serious adverse events and no treatment-related deaths. These findings support the use of adjuvant liraglutide, 3.0 mg, for weight management in patients with poor weight loss and suboptimal GLP-1 response after metabolic surgery. ClinicalTrials.gov Identifier: NCT03341429.

Estimating meaningful change for The Impact of Weight on Self-Perception (IW-SP) questionnaire among people with type 2 diabetes

PurposeThe Impact of Weight on Self-perception Questionnaire (IW-SP) is a three-item patient-reported outcome measure (PROM) instrument assessing the impact of body weight on self-perception. To date no published threshold for meaningful change exists. The objective of this study was to estimate the minimal important change (MIC) for the IW-SP among people with type 2 diabetes.MethodsResponder analyses were conducted using anchor- and distribution-based approaches with existing clinical trial data (SURPASS-2). As SURPASS-2 did not include a priori anchors, a set of alternative exploratory anchors were identified based on the MICs and items from two conceptually related measures used in the trial as well as percent change in body weight. Exploratory anchors with change estimates that were sufficiently related to change in IW-SP (r ≥ 0.30) and were not redundant with other anchors were retained for the MIC analyses. The analyses were conducted in two stages (estimation = 2/3 of sample) to derive initial IW-SP MIC estimates, and a subsequent confirmation stage (remaining 1/3 of sample).ResultsWhile the most conceptually related anchors and items performed best in responsiveness analyses, all anchors resulted in a similar estimate of minimal meaningful change for the IW-SP total score: a 1-point change in raw units (1–5-point scale), corresponding to a 25-point change for transformed scores (0–100 scale). Distribution-based analyses supported these MIC estimates. Results were similar across both stages for all analyses.ConclusionThe MIC for the IW-SP for patients with T2D is a 25-point change on the transformed score.

Effects of semaglutide on body weight in clozapine-treated people with schizophrenia and obesity: study protocol for a placebo-controlled, randomised multicentre trial (COaST)

Background People with schizophrenia die almost 20 years earlier than the general population, most commonly from avertable cardiometabolic disease. Existing pharmacological weight-loss agents including metformin have limited efficacy. Recently available glucagon-like peptide (GLP-1) receptor agonists such as semaglutide have shown promise for weight loss but have yet to be trialled in this population. Aims To examine the efficacy of semaglutide to ameliorate antipsychotic-induced obesity in people with schizophrenia who have been treated with clozapine for more than 18 weeks. Method This is a 36-week, double-blinded, randomised placebo-controlled trial. We will recruit 80 clozapine-treated patients with schizophrenia or schizoaffective disorder, aged 18–64 years, with a baseline body mass index ≥26 kg/m2, who will be randomised to subcutaneous semaglutide of 2.0 mg once a week or placebo for 36 weeks. The primary endpoint will be percentage change in body weight from baseline. Results This trial will assess the efficacy and side-effects of the GLP-1 receptor agonist semaglutide on body weight and provide evidence on the possible clinical utility of semaglutide in patients with inadequate response to metformin. The study is registered with the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) with clinical trial registration number ACTRN12621001539820. Conclusion This research could benefit individuals with schizophrenia who experience significant health issues, leading to premature mortality, owing to antipsychotic-induced weight gain. Study findings will be disseminated through peer-reviewed publications and conference presentations.

Retatrutide as a Novel Treatment for Obesity and Type 2 Diabetes

Retatrutide is a triple hormone agonist of the receptors of glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide (GIP) and glucagon that can be administered subcutaneously once a week. Different doses and escalation schedules of retatrutide were evaluated in 2 phase 2 American trials of subjects with obesity (n=338) and type 2 diabetes (n=281). In the obesity trial of 48 week-duration, percentage change in body weight from baseline after 24 weeks and 48 weeks were the primary and secondary outcomes respectively. At 24 weeks, the mean percentage decrease in weight ranged from 7.2% to 17.5% across retatrutide groups versus 1.6% with placebo. At 48 weeks, the decrease was 8.7% to 24.2% versus 2.1% with placebo. In the diabetes trial, the primary endpoint was a change in glycated hemoglobin (HbA1c) values from baseline to week 24. This trial included an active treatment group receiving dulaglutide 1.5mg once weekly. Secondary endpoints included change in HbA1c and body weight at 36 weeks. At 24 weeks, mean HbA1c reductions were 0.43% to 2.02% with retatrutide, 1.4% with dulaglutide and 0.01% with placebo. At 36 weeks, mean percentage weight reductions were 3.2% to 16.9% with retatrutide, 2.0% with dulaglutide and 3.0% with placebo. While the decrease in HbA1c levels reached a plateau at 24 weeks, weight loss in the 2 studies was progressive without evidence of attenuation effect up to the end of follow-up at 36-48 weeks. The most common adverse effects of retatrutide were gastrointestinal (GI) such as nausea, diarrhea, vomiting and constipation reported by 13-50% in the retatrutide groups compared with 35% in the dulaglutide group, and 13% in the placebo group. Discontinuation rates due to adverse effects were also higher with retatrutide being 16-17% compared with 2% with dulaglutide and 0-4% with placebo. In summary, retatrutide is highly effective drug in causing substantial weight loss and HbA1c reduction. Yet, tolerance to this drug seems sub-optimal. Phase 3 trials are urgently needed to clarify efficacy and safety of retatrutide.

Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial

We assessed the efficacy and safety of the oral glucagon-like peptide-1 analogue, semaglutide 50 mg, taken once per day versus placebo for the treatment of overweight or obesity in adults without type 2 diabetes. This randomised, double-blind, placebo-controlled, phase 3, superiority trial enrolled adults with a BMI of at least 30 kg/m2, or at least 27 kg/m2 with bodyweight-related complications and comorbidities, without type 2 diabetes. The trial was done at 50 outpatient clinics in nine countries across Asia, Europe, and North America. Participants were randomly allocated (1:1) via an interactive web-response system to oral semaglutide escalated to 50 mg, or visually matching placebo, once per day for 68 weeks, plus lifestyle intervention. Group assignment was masked for participants, investigators, and those assessing outcomes. Coprimary endpoints were the percentage change in bodyweight and whether participants reached a bodyweight reduction of at least 5% at week 68 for oral semaglutide 50 mg versus placebo, assessed regardless of treatment discontinuation or use of other bodyweight-lowering therapies (an intention-to-treat analysis). Safety was assessed in participants who received at least one dose of trial drug. This trial, registered with ClinicalTrials.gov (NCT05035095), is now complete. From Sept 13 to Nov 22, 2021, 709 participants were screened, of whom 667 were randomly assigned to oral semaglutide 50 mg (n=334) or placebo (n=333). The estimated mean bodyweight change from baseline to week 68 was -15·1% (SE 0·5) with oral semaglutide 50 mg versus -2·4% (0·5) with placebo (estimated treatment difference -12·7 percentage points, 95% CI -14·2 to -11·3; p<0·0001). More participants reached bodyweight reductions of at least 5% (269 [85%] of 317 vs 76 [26%] of 295; odds ratio [OR] 12·6, 95% CI 8·5 to 18·7; p<0·0001), 10% (220 [69%] vs 35 [12%]; OR 14·7, 9·6 to 22·6), 15% (170 [54%] vs 17 [6%]; OR 17·9, 10·4 to 30·7), and 20% (107 [34%] vs 8 [3%]; OR 18·5, 8·8 to 38·9) at week 68 with oral semaglutide 50 mg versus placebo. Adverse events were more frequent with oral semaglutide 50 mg (307 [92%] of 334) than with placebo (285 [86%] of 333). Gastrointestinal adverse events (mostly mild to moderate) were reported in 268 (80%) participants with oral semaglutide 50 mg and 154 (46%) with placebo. In adults with overweight or obesity without type 2 diabetes, oral semaglutide 50 mg once per day led to a superior and clinically meaningful decrease in bodyweight compared with placebo. Novo Nordisk.

Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial

Weight reduction is essential for improving health outcomes in people with obesity and type 2 diabetes. We assessed the efficacy and safety of tirzepatide, a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, versus placebo, for weight management in people living with obesity and type 2 diabetes. This phase 3, double-blind, randomised, placebo-controlled trial was conducted in seven countries. Adults (aged ≥18 years) with a body-mass index (BMI) of 27 kg/m2 or higher and glycated haemoglobin (HbA1c) of 7-10% (53-86 mmol/mol) were randomly assigned (1:1:1), using a computer-generated random sequence via a validated interactive web-response system, to receive either once-weekly, subcutaneous tirzepatide (10 mg or 15 mg) or placebo for 72 weeks. All participants, investigators, and the sponsor were masked to treatment assignment. Coprimary endpoints were the percent change in bodyweight from baseline and bodyweight reduction of 5% or higher. The treatment-regimen estimand assessed effects regardless of treatment discontinuation or initiation of antihyperglycaemic rescue therapy. Efficacy and safety endpoints were analysed with data from all randomly assigned participants (intention-to-treat population). This trial is registered with ClinicalTrials.gov, NCT04657003. Between March 29, 2021, and April 10, 2023, of 1514 adults assessed for eligibility, 938 (mean age 54·2 years [SD 10·6], 476 [51%] were female, 710 [76%] were White, and 561 [60%] were Hispanic or Latino) were randomly assigned and received at least one dose of tirzepatide 10 mg (n=312), tirzepatide 15 mg (n=311), or placebo (n=315). Baseline mean bodyweight was 100·7 kg (SD 21·1), BMI 36·1 kg/m2 (SD 6·6), and HbA1c 8·02% (SD 0·89; 64·1 mmol/mol [SD 9·7]). Least-squares mean change in bodyweight at week 72 with tirzepatide 10 mg and 15 mg was -12·8% (SE 0·6) and -14·7% (0·5), respectively, and -3·2% (0·5) with placebo, resulting in estimated treatment differences versus placebo of -9·6% percentage points (95% CI -11·1 to -8·1) with tirzepatide 10 mg and -11·6% percentage points (-13·0 to -10·1) with tirzepatide 15 mg (all p<0·0001). More participants treated with tirzepatide versus placebo met bodyweight reduction thresholds of 5% or higher (79-83% vs 32%). The most frequent adverse events with tirzepatide were gastrointestinal-related, including nausea, diarrhoea, and vomiting and were mostly mild to moderate in severity, with few events leading to treatment discontinuation (<5%). Serious adverse events were reported by 68 (7%) participants overall and two deaths occurred in the tirzepatide 10 mg group, but deaths were not considered to be related to the study treatment by the investigator. In this 72-week trial in adults living with obesity and type 2 diabetes, once-weekly tirzepatide 10 mg and 15 mg provided substantial and clinically meaningful reduction in bodyweight, with a safety profile that was similar to other incretin-based therapies for weight management. Eli Lilly and Company.

Tirzepatide 10 and 15 mg compared with semaglutide 2.4 mg for the treatment of obesity: An indirect treatment comparison.

To compare the efficacy of tirzepatide 10 and 15 mg with semaglutide 2.4 mg using an indirect treatment comparison. Using SURMOUNT-1 and STEP 1 trial data, mean percentage change in body weight from baseline and odds ratio (OR) of achieving 5% or greater weight loss were compared between tirzepatide 10 and 15 mg at week 72 and semaglutide 2.4 mg at week 68 using matching-adjusted indirect comparison of the efficacy estimand. Sensitivity analyses were completed using different methods, including the Bucher method, also using different estimands and/or time points. Greater reductions in percentage change in body weight were observed with tirzepatide 10 and 15 mg versus semaglutide 2.4 mg (tirzepatide 10 mg mean difference: -4.67% [95% CI -5.91%, -3.43%]; tirzepatide 15 mg mean difference: -5.92% [95% CI -7.16%, -4.68%]; both P < .001). Similarly, more participants achieved 5% or greater weight loss with tirzepatide 10 mg (OR 2.61 [95% CI 1.48, 4.57]; P < .001) and 15 mg (OR 2.75 [95% CI 1.57, 4.81]; P < .001) compared with semaglutide 2.4 mg. All sensitivity analyses were consistent, except for an OR of achieving 5% or greater weight loss with tirzepatide 10 mg using the Bucher method to analyse the treatment regimen estimand (P = .074). Currently there are no direct comparisons of tirzepatide and semaglutide for weight management. Using the matching-adjusted indirect treatment comparison method to compare the efficacy of tirzepatide and semaglutide for chronic weight management, this analysis showed greater weight loss with tirzepatide 10 and 15 mg versus semaglutide 2.4 mg.