Percent Change In Body Mass Index Research Articles

The impact of metformin on weight and metabolic parameters in patients with obesity: A systematic review and meta-analysis of randomized controlled trials.

There are conflicting data on the weight-reducing potential of metformin (MTF) in nondiabetic patients with obesity. The purpose of this systematic review and meta-analysis was to evaluate the effect of MTF on weight and cardiometabolic parameters in adults with overweight/obesity with or without nonalcoholic fatty liver disease (NAFLD) (CRD42018085512). We included randomized controlled trials (RCTs) in adults without diabetes mellitus, with mean body mass index (BMI) ≥ 25 kg/m2, with or without NAFLD, comparing MTF to placebo/control, lifestyle modification (LSM) or a US Food and Drug Administration-approved anti-obesity drug, reporting on weight or metabolic parameters, and extending over at least 3 months. We conducted a systematic search in MEDLINE, EMBASE, PubMed and the Cochrane Library without time limitation (until March 2022). We screened and selected eligible articles, abstracted relevant data, and assessed the risk of bias. All steps were in duplicate and independently. We conducted a random-effects model meta-analysis using Review Manager version 5.3, with prespecified subgroup analyses in case of heterogeneity. We identified 2650 citations and included 49 trials (55 publications). Compared to placebo, MTF was associated with a significant reduction in BMI (mean difference [MD] -0.56 [-0.74, -0.37] kg/m2; p < 0.0001), at doses ranging from 500 to 2550 mg/day, and with a significant percentage change in BMI of -2.53% (-2.90, -2.17) at the dose 1700 mg/day. There was no interaction by baseline BMI, MTF dose or duration, nor presence or absence of NAFLD. There was no significant difference between MTF and LSM. Orlistat was more effective than MTF (at doses of 1000-1700 mg/day) in terms of weight loss, with an MD in BMI of -3.17 (-5.88; -0.47) kg/m2, favouring the former. Compared to placebo/control, MTF improved insulin parameters, while no effect was detected when compared to LSM. A few small trials showed heterogenous effects on liver parameters in patients with NAFLD treated with MTF compared to placebo/control. There was a large variability in the expression of outcome measures and RCTs were of low quality. In conclusion, MTF was associated with a modest weight reduction in obese nondiabetic patients. Further high-quality and better powered studies are needed to examine the impact of MTF in patients with insulin resistance and NAFLD.

Impact of rehabilitation dose on body mass index change in older acute patients with stroke: a retrospective observational study.

It is established that a low body mass index (BMI) correlates with a diminished home discharge rate and a decline in activities of daily living (ADL) capacity among elderly stroke patients. Nevertheless, there exists a paucity of knowledge regarding strategies to mitigate BMI reduction during the acute phase. This investigation seeks to elucidate the impact of rehabilitation dose, as determined by both physical and occupational therapy, on BMI alterations, positing that a heightened rehabilitation dose could thwart BMI decline. This retrospective, observational study was conducted in the stroke unit of a university hospital. Enrollees comprised individuals aged ≥65 years, hospitalized for stroke, and subsequently relocated to rehabilitation facilities between January 2019 and November 2020. The percentage change in BMI (%ΔBMI) was calculated based on BMI values at admission and discharge. Multivariate multiple regression analysis was employed to ascertain the influence of rehabilitation dose on %ΔBMI. A total of 187 patients were included in the analysis, of whom 94% experienced a reduction in BMI during acute hospitalization. Following adjustment for sociodemographic and clinical factors, multivariable analyzes revealed a positive association between rehabilitation dose and %ΔBMI (β = 0.338, p < 0.001). The findings of this study suggest that, in the context of acute stroke treatment, an augmented rehabilitation dose is associated with a diminished decrease in BMI.

FRI065 Trial Design Of A Double-blind, Randomized, Placebo-controlled, Phase 3 Study Of Setmelanotide In Patients With Hypothalamic Obesity

Abstract Disclosure: C.L. Roth: Other; Self; Study funding from Rhythm Pharmaceuticals, Inc. A.H. Shoemaker: Advisory Board Member; Self; Rhythm Pharmaceuticals, Inc., Saniona. Other; Self; Study funding from Rhythm Pharmaceuticals, Inc. M. Gottschalk: Advisory Board Member; Self; Rhythm Pharmaceuticals, Inc. Consulting Fee; Self; Rhythm Pharmaceuticals, Inc. Other; Self; Study funding from Rhythm Pharmaceuticals, Inc. J.L. Miller: Other; Self; Study funding from Rhythm Pharmaceuticals, Inc. G. Yuan: Employee; Self; Rhythm Pharmaceuticals, Inc. Stock Owner; Self; Rhythm Pharmaceuticals, Inc. S. Malhotra: Employee; Self; Rhythm Pharmaceuticals, Inc. Stock Owner; Self; Rhythm Pharmaceuticals, Inc. C. Scimia: Employee; Self; Rhythm Pharmaceuticals, Inc. Stock Owner; Self; Rhythm Pharmaceuticals, Inc. S. McCormack: None. M.J. Abuzzahab: Consulting Fee; Self; Pfizer, Inc., Rhythm Pharmaceuticals, Inc., Consynance. Other; Self; Study funding from Rhythm Pharmaceuticals, Inc., Ascendis, NovoNordisk, Levo Pharmaceuticals, Lumos, Saniona, and Soleno. Background: Damage to the hypothalamus via physical trauma, tumors, surgical resection, and/or radiotherapy can impair the melanocortin signaling pathway and reduce energy expenditure, potentially leading to hypothalamic obesity, a severe form of obesity with no current specific therapeutic option. Recently, the selective melanocortin-4 receptor agonist setmelanotide demonstrated reduction in weight and hunger for patients with hypothalamic obesity who were treated in a Phase 2 trial. We describe the study design of a planned double-blind, randomized, placebo-controlled, Phase 3 trial of setmelanotide in patients with hypothalamic obesity. Methods: Approximately 120 patients will be enrolled across ≤35 sites globally. Eligibility criteria include age ≥4 years with documented evidence of acquired hypothalamic obesity with associated weight gain before and/or with tumor treatment and body mass index (BMI) ≥30 kg/m2 (≥18 years) or BMI ≥95th percentile (≥4 to &amp;lt;18 years). Key exclusion criteria include diagnosis of syndromic obesity, weight or BMI loss &amp;gt;2% based on age in the prior 3 months, bariatric surgery within the past 2 years, glycated hemoglobin &amp;gt;11.0%, and glomerular filtration rate &amp;lt;30 mL/min/1.73 m2. Patients will be randomized 2:1 and stratified by age to receive setmelanotide or placebo. Setmelanotide will be titrated over 2-8 weeks to a maximum daily subcutaneous dose of 1.5-3.0 mg based on age and weight. Double-blind treatment will continue for up to 60 weeks, with visits (in-clinic, at-home, or telehealth) at Weeks 20, 28, 36, 44, and 52 and at an end-of-treatment clinic visit at Week 60. The primary endpoint is the mean percent change in BMI after 52 weeks of treatment for setmelanotide versus placebo. Key secondary endpoints after 52 weeks are the proportion of patients aged ≥18 years with ≥5% reduction in BMI, proportion of patients aged &amp;lt;18 years with ≥0.2-point reduction in BMI Z score, and mean change in weekly average of the daily “most hunger” score in patients aged ≥12 years. Additional secondary endpoints include proportion of patients achieving ≥2-point reduction in weekly average of the daily maximal hunger score, Symptoms of Hyperphagia total score, additional weight-related parameters, and quality of life outcomes. Exploratory endpoints include change after 52 weeks in physical activity (measured by acDetigraphy), fatigue (via Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue©/Peds FACIT-F© scale), Impacts of Hyperphagia score, caregiver health status (via EuroQol-5-Dimension scale), cardiometabolic parameters, and waist circumference. Safety will be assessed by the frequency and severity of adverse events. Conclusions: This Phase 3 trial designed to assess the efficacy and safety of setmelanotide for weight loss and hunger reduction in patients ≥4 years of age with acquired hypothalamic obesity is planned to initiate in early 2023. Presentation: Friday, June 16, 2023

A Randomised Control Trial to Explore the Impact and Efficacy of the Healum Collaborative Care Planning Software and App on Condition Management in the Type2 Diabetes Mellitus Population in NHS Primary Care.

Effective and scalable solutions to support management of Type2 Diabetes (T2D) at a distance are a priority for health systems worldwide. The use of personalised care planning has been shown to be effective at improving the health outcomes and the experience of care amongst people with T2D and other long-term health conditions. Here we describe a specific example of such an intervention. The sample comprised 197 participants with T2D randomised to either the active intervention group with digital health planning (App + usual care), with 115 participants, or the control group (usual care), with 82 participants. We analysed data in relation to changes in body mass index (BMI)andglycated haemoglobin (HbA1c) over a 6-month follow-up period. We also analysed responses to questionnaires sent out and held interviews with participants that were in the active treatment group and therefore had a care plan created and access to an app. The active treatment group had significant reductions in HbA1c (p < 0.01) and BMI (p < 0.037) vs the control group (no significant change). The average percentage change in HbA1c for the treatment group over 6months was - 7.4% (± SE 1.4%), compared with 1.8% (± SE 2.1%) for the control group. The average percentage change in BMI for the treatment group was - 0.7% (± SE 0.4%) and it was - 0.2% (± SE 0.5%) for the control group. A higher percentage of the active treatment group reduced their HbA1c and BMI than the control group. For HbA1c, 72.4% of the active treatment group reduced their HbA1c, compared to 41.5% of the control group. For BMI, 52.7% of the active treatment group experienced a reduction, compared to 42.9% for the control group. Self-measured quality of life (QoL) improved for patients in the active treatment group, shown by an increase in theirpre-trial to post-trial EQ-5D-5L rating by an average of 0.0464 (± SE 0.0625), compared to a decrease of 0.0086 (± SE 0.0530) for the control group. The average EQVAS score also increased pre- to post-trial for the active treatment group, on average by 8.2%, whereas it decreased by an average of - 2.8% for the control group. These findings point to how the provision of personalised plans of care, support and education linked to a mobile app, can result in HbA1c and BMI reduction for many individuals with T2D. The use of a patient management app as well as a personalised care plan also led to an improvement in patient self-rated QoL and engagement.

Efficacy of deep brain stimulation for the treatment of anorexia nervosa: a systematic review and network meta-analysis of patient-level data.

Deep brain stimulation (DBS) has been approved as a therapy for movement disorders and obsessive-compulsive disorder. Recently, DBS has been studied in patients with anorexia nervosa (AN), which is a debilitating and life-threatening psychiatric disorder. Several stimulation locations have been tested without a clear indication of the best region. In this systematic review and network meta-analysis, the authors used patient-level data to identify stimulation targets with the greatest evidence for efficacy in increasing body mass index (BMI). A systematic search was performed on or before August 4, 2022, using PubMed/MEDLINE, Ovid, and Scopus. Articles were included if patient-level data were presented, patients were diagnosed with AN and treated with DBS, and 6 months or more of postoperative follow-up data were reported. Quality and risk of bias were assessed with the NIH assessment tools. Patient data were collected and stratified by stimulation location. A network meta-analysis was performed. This review was written in accordance with PRISMA guidelines for systematic reviews. Eleven studies consisting of 36 patients were included. The mean age and BMI at the time of surgery were 38.07 (SD 11.64) years and 12.58 (SD 1.4) kg/m2, respectively. After 6 months of DBS, a significant difference in percentage change in BMI was found between the nucleus accumbens and subcallosal cingulate cortex (SCC) (SMD 0.78; 95% CI 0.10, 1.45) and between the SCC and ventral anterior limb of the internal capsule (SMD -1.51; 95% CI -2.39, -0.62). Similarly, at 9-12 months, a significant difference in percentage change in BMI was found between the SCC and ventral anterior limb of the internal capsule (SMD -1.18; 95% CI -2.21, -0.15). With hierarchical ranking, this study identified SCC as the most supported stimulation location for BMI change at 6 and 9-12 months (P-scores 0.9449 and 0.9771, respectively). Several DBS targets have been tested for AN, and this study identified the SCC as the most supported region for BMI change. However, further studies with blinded on/off periods are necessary to confirm this finding.

PS-C18-2: BODY MASS INDEX TRAJECTORY AND TECHNIQUE FAILURE OR DEATH IN PATIENTS INITIATING PERITONEAL DIALYSIS

Objective: A decreased body mass index (BMI) over time, as a nutritional status marker, is associated with the poor prognosis of patients undergoing hemodialysis; however, this association has not been studied in patients with peritoneal dialysis (PD). Thus, this study aimed to evaluate the association between BMI trajectory and survival of patients initiating PD. Design and Method: BMI trajectory was defined as percent changes in BMI before PD catheter insertion until six months after insertion. The association of BMI trajectory with technique failure or all-cause death at six months after PD catheter insertion until October 2021 was analyzed. Results: This retrospective cohort study included 122 patients (aged 61.1 ± 12.1 years; 90 males) who underwent PD catheter insertion between January 2008 and March 2020. The median follow-up period was 43.1 (interquartile range, 21.2 - 78.8) months. The mean 6-month percent change in BMI was - 1.98% ± 6.91%, and patients were categorized into tertiles based on BMI trajectory. The adjusted Cox regression analysis for age, sex, Charlson comorbidity index, estimated glomerular filtration rate, and geriatric nutritional risk index revealed a significantly higher rate of technical failure or all-cause mortality (hazard ratio, 2.48; 95% confidence interval: 1.41 - 4.37) in patients with the lowest tertile (T1, BMI trajectory: &lt; - 4.13%) compared to patients with middle tertile, the reference group (T2, BMI trajectory: - 4.13 - 0.67%). The risk was not significantly higher in patients with the highest tertile (T3, BMI trajectory: &gt; 0.67%) than T2 group (hazard ratio: 1.18; 95% confidence interval: 0.66 - 2.11). Conclusions: A decreased BMI (not increased) over time is independently associated with technique failure or all-cause death among patients initiating PD, highlighting the importance of BMI trajectory as a novel prognostic marker. Moreover, further studies are warranted to investigate the interventions, including BMI optimization, as a novel therapeutic target to improve technique and patient survival.

OR10-1 Body Mass Index and Weight Reductions in Patients With Obesity Due to Heterozygous Variants in POMC, PCSK1, and LEPR After 1 Year of Setmelanotide

Abstract Background The melanocortin-4 receptor (MC4R) pathway is a key regulator of energy balance. Heterozygous variants of the genes for proopiomelanocortin (POMC), leptin receptor (LEPR), and proprotein convertase subtilisin/kexin type 1 (PCSK1) upstream of MC4R can result in impaired signaling in the MC4R pathway. This impaired signaling can lead to hyperphagia and early-onset, severe obesity. Setmelanotide (SET), an MC4R agonist, reduced weight and hunger after 3 months in patients with obesity due to these heterozygous variants in an earlier Phase 2 study. The current analysis is the first to assess continued efficacy of an additional year of SET treatment in patients with obesity due to heterozygous affectation of POMC, PCSK1, and LEPR. Methods Patients aged ≥6 years with obesity due to heterozygous variants in POMC, PCSK1, and LEPR were eligible for this long-term extension (LTE) trial (NCT03651765) after completing an index trial in which they received SET and demonstrated clinical benefit and acceptable safety as determined by the investigator. Patients received a minimum of 4 months of SET treatment in the index trial and began the LTE immediately following the completion of the index trial. Study visits occurred every 3 months and evaluated changes in body weight measures and assessed safety and tolerability. The current analysis reports outcomes after 1 year total of SET treatment across the index and LTE trials, relative to index trial baseline. Results As of October 29, 2021, 35 patients with obesity heterozygous for POMC, PCSK1, and LEPR had enrolled in the index trial, with 16, 17, and 17 patients continuing into the LTE trial and receiving at least 6, 9, and 12 months of treatment with SET, respectively. At index trial baseline, mean (standard deviation [SD]) body mass index (BMI) for all index trial patients was 50.26 (9.41) kg/m2, body weight in patients ≥18 years old was 142.97 (28.70) kg, and BMI Z score in patients &amp;lt;18 years old was 4.04 (0.65). Mean (SD) percent change in BMI was −6.93% (9.13%; n=16), −8.14% (10.13%; n=17), and −7.83% (9.69%; n=17) after 6, 9, and 12 months of treatment, respectively. Of 15 patients ≥18 years old, the mean (SD) percent change in body weight was −10.24% (7.90%; n=15) after 12 months. For the 1 patient &amp;lt;18 years old, mean change in BMI Z score was 0.64 after 12 months. No new safety concerns emerged during the LTE and 1 patient discontinued due to an adverse event, likely unrelated to treatment. Conclusions Treatment with SET had continued efficacy in patients with obesity due to heterozygous variants in POMC, PCSK1, and LEPR after 1 year of treatment. These data support the continued investigation of SET in these patients, which is underway in the Phase 3 EMANATE trial (NCT05093634). Presentation: Sunday, June 12, 2022 11:00 a.m. - 11:15 a.m.

ODP605 Body Mass Index and Weight Reductions in Patients With SRC1 Genetic Variant Obesity After 1 Year of Setmelanotide

Abstract Background The melanocortin-4 receptor (MC4R) pathway is a key regulator of energy balance. Steroid receptor coactivator 1 (SRC1; also known as NCOA1) is a transcriptional coactivator that regulates proopiomelanocortin (POMC) expression in the MC4R pathway. Certain SRC1 variants impair MC4R signaling and are associated with hyperphagia (pathologic insatiable hunger) and early-onset, severe obesity. Treatment with setmelanotide, an MC4R agonist, resulted in weight and hunger reductions after 3 months in patients with SRC1 variant obesity in a Phase 2 study. This analysis is the first to assess the continued efficacy of 1 year of setmelanotide treatment in patients with SRC1 variant obesity. Methods Patients with SRC1 variant obesity aged ≥6 years were eligible for this long-term extension (LTE) trial (NCT03651765) if they completed an index trial in which they received setmelanotide and demonstrated clinical benefit on the basis of efficacy and acceptable safety as determined by the investigator. Patients received a minimum of 4 months of setmelanotide treatment as part of the index trial and began the LTE immediately following completion. Study visits occurred approximately every 3 months. Study objectives included evaluating changes in weight-related measures and tolerability. The current analysis reports outcomes after 1 year of setmelanotide treatment across the index and LTE trials, relative to index trial baseline. Results As of October 29, 2021, 30 patients (20 ≥18 years old and 10 &amp;lt;18 years old) with SRC1 variant obesity enrolled in the index trial. Seventeen patients entered the LTE; at the time of analysis, 16, 11, and 8 patients had received at least 6, 9, and 12 months of treatment, respectively. At index trial baseline, mean (standard deviation [SD]) body mass index (BMI) for all patients was 45.4 (11.3) kg/m2, body weight in patients ≥18 years old was 139.7 (25.1) kg, and BMI Z score in patients &amp;lt;18 years old was 2.99 (0.63). After 6, 9, and 12 months of treatment, mean (SD) percent change in BMI was −5.7% (5.6%; n=16), −7.8% (5.8%; n=11), and −10.1% (9.4%; n=8), respectively. Mean (SD) percent change in body weight in patients ≥18 years old at 6, 9, and 12 months was −6.7% (6.1%; n=11), −9.9% (7.4%; n=8), and −11. 0% (8.6%; n=7), respectively. The mean (SD) change in BMI Z score was −0.35 (0.35; n=7), −0.42 (0.23; n=5), and −0.67 (0.57; n=3) after 6, 9, and 12 months, respectively. No new safety concerns emerged during long-term treatment, and no patients discontinued because of an adverse event. Conclusions One year of setmelanotide treatment led to clinical weight benefits in patients with SRC1 variant obesity. These data support the continued investigation of setmelanotide in this population, which is underway in the Phase 3 EMANATE trial (NCT05093634). Presentation: No date and time listed

ODP606 Long-term Efficacy of Setmelanotide in Patients With Bardet-Biedl Syndrome

Abstract Objective Bardet-Biedl syndrome (BBS) is a rare genetic disease characterized by hyperphagia (pathologic insatiable hunger) and early-onset, severe obesity believed to be driven by impaired signaling in the melanocortin-4 receptor (MC4R) pathway. In a Phase 2 and a pivotal Phase 3 trial, treatment with the MC4R agonist setmelanotide produced beneficial reductions in weight, body mass index (BMI), BMI Z score, and hunger in patients with BBS at ∼1 year. The current analysis is the first to assess the continued long-term efficacy of setmelanotide administration in patients with BBS over ∼2 years. Methods Patients with BBS aged ≥6 years were eligible for this observational long-term extension (LTE) trial (NCT03651765) if they completed an index trial in which they received setmelanotide and demonstrated clinical benefit and acceptable safety as determined by the investigator. Patients received up to ∼12 months of setmelanotide as part of the index trial and began the LTE immediately following completion of the index trial. Study visits occurred approximately every 3 months in the LTE trial. Study objectives included evaluating changes in body weight and assessing safety and tolerability. The current analysis reports outcomes after ∼1 year of additional setmelanotide administration during the LTE trial, relative to index trial baseline. Results As of October 29, 2021, 54 patients with BBS enrolled the index trial, including 28 patients &amp;lt;18 years old and 26 patients ≥18 years old. Among patients who entered the LTE trial, 30 and 19 received at least 18 and 24 months of treatment, respectively. At their enrollment in their index trial, participants’ baseline mean (standard deviation [SD]) BMI was 42.2 (9.2) kg/m2, body weight in patients ≥18 years old was 132.3 (20.9) kg, and BMI Z score in patients &amp;lt;18 years old was 3.5 (0.76). Across age groups, after 18 and 24 months of treatment, mean (SD) percent change in BMI was −9.5% (10.5%; n=30) and −14.3% (11.6%; n=19), respectively. Mean (SD) percent change in body weight in those ≥18 years old after 18 and 24 months was −8.6% (10.3%; n=15) and −14.9% (10.4%; n=6), respectively. The mean (SD) change in BMI Z score in patients &amp;lt;18 years old after 18 and 24 months was −0.83 (0.50; n=13) and −0.72 (0.54; n=12), respectively. No new safety signals were observed during long-term setmelanotide administration. One patient discontinued because of an adverse event (hallucination; unlikely to be related to setmelanotide). Conclusions Clinically beneficial effects of setmelanotide on body weight-related measures continued to be observed in patients with BBS for up to 2 years. Only 1 patient discontinued the LTE trial due to an adverse event, suggesting setmelanotide continued to have clinical benefit and was generally well tolerated. These data support the long-term use of setmelanotide in patients with BBS. Presentation: No date and time listed

RF24 | PSUN91 Body Mass Index and Weight Reduction in Patients With SH2B1 Genetic Variant Obesity After One Year of Setmelanotide

Abstract Background SH2B adaptor protein 1 (SH2B1) binds to Janus kinase 2 and enhances leptin signaling through the central melanocortin-4 receptor (MC4R) pathway, a key regulator of energy balance. Variants in SH2B1 or a 220–kilobase pair distal deletion of chromosome 16p11.2, including SH2B1, are associated with hyperphagia (pathologic insatiable hunger), severe early-onset obesity, reduced final height, and insulin resistance. Setmelanotide, an MC4R agonist, produced significant weight and hunger reduction after 3 months in patients with SH2B1 heterozygous variants or 16p11.2 deletion in a Phase 2 study. This analysis is the first to assess the continued efficacy of ∼1 year of setmelanotide treatment in patients with SH2B1 genetic obesity. Methods Patients aged ≥6 years with SH2B1 heterozygous variants or 16p11.2 deletion encompassing SH2B1 were eligible for this long-term extension (LTE) trial (NCT03651765) if they completed a prior (index) trial in which they received setmelanotide and demonstrated clinical benefit based on weight and hunger results, and acceptable safety as determined by the investigator. Patients received a minimum of 4 months of setmelanotide treatment as part of the index trial and began the LTE immediately following the completion of the index trial. Study visits occurred approximately every 3 months. Study objectives included evaluating changes in body weight measures and assessing tolerability. The current analysis reports outcomes after ∼1 year of setmelanotide treatment across the index and LTE trials relative to index trial baseline. Results As of October 29, 2021, 35 patients with obesity and SH2B1 heterozygous variants or 16p11.2 deletion had enrolled in the index trial. Of patients entering the LTE, 19, 15, and 14 had received at least 6, 9, and 12 months of treatment, respectively. At index trial baseline, mean (standard deviation [SD]) body mass index (BMI) for all patients was 47.2 (12.8) kg/m2, body weight in patients aged ≥18 years (n=22) was 139.7 (35.4) kg, and BMI Z-score in patients aged &amp;lt;18 years (n=13) was 3.56 (0.60). Mean (SD) percent change in BMI was −3.4% (8.1%; n=19), −5.9% (10.0%; n=15), and −9.7% (8.0%; n=14) after 6, 9, and 12 months of treatment. Mean (SD) percent change in body weight in patients aged ≥18 years was −4.4% (5.0%; n=9), −6.8% (5.0%; n=7), and −7.7% (10.0%; n=8) after 6, 9, and 12 months, respectively. Mean (SD) change in BMI Z-score was −0.55 (0.17; n=6) after 12 months. No patients discontinued due to adverse events during the LTE . No new safety concerns emerged during long-term treatment. Conclusions Setmelanotide treatment provided clinically meaningful reductions in weight-related measures in patients with SH2B1 heterozygous variants or 16p11.2 deletion up to ∼1 year. These data support the continued investigation of setmelanotide in this population, which is underway in the planned Phase 3 EMANATE trial (NCT05093634). Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 12:30 p.m. - 12:35 p.m.

The potential role of selected body composition phenotypes in the interpretation of the exercise-induced components of the insulin-like growth factor systems

Introduction: Increased adiposity leads to impaired physiologic growth hormone secretion and low and high body mass index (BMI) values increase health risks. However, BMI only measures results in variations in fat-free mass (FFM), fat-free mass index (FFMI), normalized fat-free mass index (NFMI), and body fat mass (BFM). This study evaluated the insulin-like growth factor system responses to the given exercise and their interaction with the changes in BMI, FFM, FFMI, and NFFMI in healthy male participants. Material and methods: A randomized controlled trial with a parallel groups study design was used. Thirty healthy male participants (age: 21.33 ±1.24 years) were divided into three categories: high-intensity incremental (n = 12) and low-intensity constant (n = 12) cycling training groups and control group (n = 6). Training groups performed three times per week throughout eight weeks. VO2max, serum biomarkers, and neuromuscular performance were measured both during baseline and follow-up. Results: The changes in bioavailable IGF were not correlated with BMI (r = –.267), whereas they significantly positively correlated with BFM (r = .321), and inversely significantly correlated with FFM (r = –.472), FFMI (r = –.425), and NFFMI (r = –.379) after 8 weeks of exercise. For relative bioavailable IGF changes, FFM (r2 = 0.17), FFMI (r2 = 0.18), and NFFMI (r2 = 0.14) percent change explained nearly three times the variance as BMI percent change (r2 = 0.07). Conclusions: Increased bioavailable IGF-I suggests an increased anticatabolic effect and inverse interaction with body composition phenotypes following exercise. The partitioning of BMI into FFM, FFMI, and NFFMI rather than relying on sole measures of BMI seem to offer more precise results in the assessment of the interactions between the body composition, neuromuscular performance adjusted with body composition phenotypes, and training-induced changes in insulin-like growth factor system.

Phentermine/Topiramate for the Treatment of Adolescent Obesity

BackgroundAntiobesity medication may be useful for the treatment of pediatric obesity, yet few safe and effective options exist. We evaluated phentermine/topiramate (PHEN/TPM) for weight management in adolescents with obesity.MethodsThis 56-week, randomized, double-blind trial enrolled adolescents 12 to less than 17 years of age with obesity. Participants were randomly assigned 1:1:2 to receive either placebo (n=56), mid-dose PHEN/TPM (7.5 mg/46 mg; n=54), or top-dose PHEN/TPM (15 mg/92 mg; n=113), respectively. All participants received lifestyle therapy. The primary end point was mean percent change in body-mass index (BMI) from randomization to week 56.ResultsParticipants had a mean (±SD) age of 14.0±1.4 years and a mean (±SD) BMI of 37.8±7.1 kg/m2; 54.3% were female. The primary end point of percent change in BMI at week 56 showed differences from placebo of −10.44 percentage points (95% CI, −13.89 to −6.99; P<0.001) and −8.11 percentage points (95% CI, −11.92 to −4.31; P<0.001) for the top and mid doses of PHEN/TPM, respectively. Differences from placebo in percent change in triglycerides nominally favored PHEN/TPM (mid dose, −21%; 95% CI, −40 to −2; and top dose, −21%; 95% CI, −38 to −4), as did differences in percent change in high-density lipoprotein cholesterol (HDL-C) (mid dose, 10%; 95% CI, 3 to 18; and top dose, 9%; 95% CI, 2 to 15). The incidence of participants reporting at least one adverse event was 51.8%, 37.0%, and 52.2% in the placebo, mid-dose, and top-dose groups, respectively. Serious adverse events were reported for two participants in the top-dose group.ConclusionsPHEN/TPM at both the mid and top doses offered a statistically significant reduction in BMI and favorably impacted triglyceride and HDL-C levels in adolescents with obesity. (Funded by VIVUS LLC, with project support provided by Covance LLC; ClinicalTrials.gov number, NCT03922945.)

Efficacy of Green Tea Consumption on Reducing Body Mass Index and Insulin Resistance: A Meta‐Analysis

Introduction Obesity and diabetes are ongoing public health concerns in the United States, especially in rural communities. Obesity is a leading cause of many conditions such as cardiovascular diseases and diabetes. Diabetes, specifically Type 2 Diabetes Mellitus (T2DM), is a leading cause of many conditions such as heart disease and vision problems. Commercially available green tea (Camellia sinensis) products may promote weight loss and insulin sensitivity as indicated by change in Body Mass Index (BMI) and insulin-resistance markers, which could provide potential benefit in the adjunctive management of obesity and diabetes. We conducted a meta-analysis on recent randomized controlled trials (RCTs) to test the hypothesis that consumption of green tea (GT) or green tea extract (GTE) for over four weeks can lead to a decrease in BMI and/or Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index. Our study results will provide updated guidance on dietary recommendations and offer insight into effect sizes translatable to the general population. Methods Electronic databases including PubMed were searched for parallel-designed and double-blinded RCTs published between 2010 and 2020 that examined the effect of GT and GTE on BMI and/or HOMA-IR Index. Two authors independently reviewed articles for inclusion with differences resolved by consensus. Three authors independently assessed studies to assign risk of bias scores. Heterogeneity of studies was evaluated through use of forest plots and the I2 statistic using RevMan5 software. When necessary, data of varying measurement units were synthesized by meta-analysis. Results Eleven studies involving over 800 subjects were included. Daily doses of green tea ranged from 379 mg standardized extract to 20 mg green tea solids. Duration of interventions ranged from 4 to 48 weeks. Preliminary analysis indicates a statistically significant (p<0.05) percentage change in BMI and HOMA-IR index with mean effect sizes of –2.29% (95% CI –4.45%, -0.13%, p=0.04) and –19.75% (95% CI -35.11%, -4.39%, p=0.01), respectively. Most included studies had unknown or high risk of bias. Conclusions Included studies were widely varied in patient selection, dosing, dosing strategy, and outcome measurements. However, these differences suggest broader applicability of the results. Adding green tea may be an accessible, inexpensive and well-tolerated dietary change that may reduce the risk of chronic diseases associated with obesity and diabetes. Future research opportunities include conducting large RCTs to address the public health concern of obesity, diabetes and preventive medicine.

Effect of liraglutide treatment on body mass index and weight parameters in children and adolescents with type 2 diabetes: Post hoc analysis of the ellipse trial.

SummaryBackgroundWeight loss in children and adolescents with type 2 diabetes (T2D) is associated with improved glycaemic control.ObjectivesTo assess the effects of liraglutide vs placebo on body mass index (BMI) and weight parameters in children and adolescents with T2D using data from the ellipse trial (NCT01541215).MethodsThe ellipse trial randomized participants (10‐<17 years old, BMI >85th percentile, T2D, glycated haemoglobin [HbA1c] 7.0%‐11.0% [if diet‐ and exercise‐treated] or 6.5% to 11.0% [if treated with metformin, basal insulin or both]) to liraglutide or placebo. This post‐hoc analysis evaluated changes from baseline to weeks 26 and 52 in absolute BMI, percent change in BMI and other weight‐related parameters. Changes were assessed by liraglutide overall (all doses) and liraglutide by dose (0.6, 1.2 and 1.8 mg/day) vs placebo using a pattern mixture model of observed data, with missing observations imputed from each treatment group.ResultsIn total, 134 participants were included. There were statistically significant differences between groups in certain parameters, including absolute BMI (estimated treatment difference [ETD] –0.89 kg/m2; 95% confidence interval [CI] –1.71,–0.06) and percent change in BMI (ETD –2.73%; 95% CI –5.15,–0.30) at week 52, but none at week 26. Dose‐dependent effects were not observed for liraglutide vs placebo for all BMI/weight parameters.ConclusionsCompared with placebo, liraglutide was associated with statistically significant reductions in BMI/weight parameters at week 52, but not week 26, in children and adolescents with T2D.

Weight Change After Subthalamic Nucleus Deep Brain Stimulation in Patients With Isolated Dystonia.

Purpose: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment method for advanced Parkinson's disease (PD) and isolated dystonia and provides marked improvement of major motor symptoms. In addition, non-motor effects have been reported including weight gain (WG) in patients with PD after STN-DBS. However, it is still unclear whether patients with isolated dystonia also experience WG.Methods: Data from 47 patients with isolated dystonia who underwent bilateral STN-DBS surgery between October 2012 and June 2019 were retrospectively collected. The severity of dystonia was assessed via the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS). Changes in the body mass index (BMI) and BFMDRS score were analyzed using paired Student's t-tests. Regression analysis was performed to identify factors that affected the BMI after surgery.Results: Postoperative WG was observed in 78.7% of patients. The percentage of overweight and obese patients increased from 25.5% (before STN-DBS) to 48.9% (at the last follow-up). The mean BMI and mean percentage change in BMI increased by 1.32 ± 1.83 kg/m2 (P < 0.001) and 6.28 ± 8.34%, respectively. BMI increased more in female than in male patients. At the last follow-up, BFMDRS movement and disability scores improved by 69.76 ± 33.23% and 65.66 ± 31.41%, respectively (both P < 0.001). The final regression model analysis revealed that sex and preoperative BMI alone were independently associated with BMI change (P < 0.05).Conclusions: STN-DBS is associated with postoperative WG with patients with isolated dystonia. WG is more prominent in female patients and is associated with preoperative weight but not with the efficacy of STN-DBS on motor symptoms.

Variability and change over time of weight and BMI among adolescents and adults with Prader-Willi syndrome: a 6-month text-based observational study

BackgroundPrader-Willi syndrome (PWS) is a rare neurodevelopmental disorder in which hyperphagia (excessive appetite) is a hallmark feature. Understanding how weight changes over time in this population is important for capturing the contemporary natural history of the disorder as well as assessing the impact of new treatments for hyperphagia. Therefore, we aimed to determine the feasibility of a remote assessment of weight change over time in PWS.MethodsWe developed a text message-based, prospective cohort study of adolescents and adults with PWS to assess changes in weight and body mass index (BMI) over a six-month period. Weight was collected weekly, while changes in height, living situation, access to food, activity level, and medication were collected at three-month intervals.ResultsOne hundred and sixty-five participants enrolled in the study, with a mean age of 19.7 years (range 12–48). There was considerable variability in weight across participants (range: 76.8–207.7 kg). Thirty-three percent of the participants were normal weight, while 15% were overweight and 52% were obese. Overall, the weight of the study participants increased over the study period (mean weight change + 2.35%), while BMI was relatively stable, albeit high (mean BMI of 31.4 at baseline, mean BMI percent change + 1.42%). Changes in living situation, activity, food access, and medication had limited impact on weight and BMI changes. Multivariable analysis found that time, sex, age, and percentage of life on growth hormone (GH) therapy were statistically significant fixed effects. Participants submitted more than 95% of possible weight data points across the 26 weeks of the study.ConclusionsThis remote, observational study of weight change in PWS showed small increases in weight and BMI over a six-month period. Participants were highly compliant with this text message-based study, suggesting that mobile technology-based data collection was manageable for the participants. We anticipate that the results of this study will inform clinical trials for hyperphagia/obesity related therapies in PWS and provide a basis for understanding the efficacy of new therapies for hyperphagia in the real-world setting.

Impact of Changes in Chain Restaurant Calories over Time on Obesity Risk.

Prior research on the restaurant environment and obesity risk is limited by cross-sectional data and a focus on specific geographic areas. To measure the impact of changes in chain restaurant calories over time on body mass index (BMI). We used a first-difference model to examine whether changes from 2012 to 2015 in chain restaurant calories per capita were associated with percent changes in BMI. We also examined differences by race and county income, restaurant type, and initial body weight categories. USA (207 counties across 39 states). 447,873 adult patients who visited an athenahealth medical provider in 2012 and 2015 where BMI was measured. Percent change in objectively measured BMI from 2012 to 2015. Across all patients, changes in chain restaurant calories per capita were not associated with percent changes in BMI. For Black or Hispanic adults, a 10% increase in exposure to chain restaurant calories per capita was associated with a 0.16 percentage-point increase in BMI (95% CI 0.03, 0.30). This translates into a predicted weight increase of 0.89 pounds (or a 0.53% BMI increase) for an average weight woman at the 90th percentile of increases in the restaurant environment from 2012 to 2015 versus an increase 0.39 pounds (or 0.23% BMI increase) at the 10th percentile. Greater increases in exposure to chain restaurant calories also significantly increased BMI for Black or Hispanic adults receiving healthcare services in lower-income counties (0.26, 95% CI 0.04, 0.49) and with overweight/obesity (0.16, 95% CI 0.04, 0.29). Generalizability to non-chain restaurants is unknown and the sample of athenahealth patients is relatively homogenous. Increased exposure to chain restaurant calories per capita was associated with increased weight gain among Black or Hispanic adults.

Longitudinal associations between BMI change and the risks of colorectal cancer incidence, cancer-relate and all-cause mortality among 81,388 older adults

BackgroundIt remains controversial whether weight change could influence the risks of colorectal cancer (CRC) and mortality. This study aimed to quantify the associations between full-spectrum changes in body mass index (BMI) and the risks of colorectal cancer (CRC) incidence, cancer-related and all-cause mortality among midlife to elder population.MethodsA total of 81,388 participants who were free of cancer and aged 55 to 74 years from the Prostate, Lung, Colorectal, and Ovarian (PLCO) screening program were involved. The percentage change of BMI was calculated as (BMI in 2006 - BMI at baseline)/BMI at baseline, and was categorized into nine groups: decrease (≥ 15.0%, 10.0–14.9%, 5.0–9.9%, 2.5–4.9%), stable (decrease/increase < 2.5%), increase (2.5–4.9%, 5.0–9.9%, 10.0–14.9%, ≥ 15.0%). The associations between percentage change in BMI from study enrolment to follow-up (median: 9.1 years) and the risks of CRC and mortality were evaluated using Cox proportional hazard regression models.ResultsAfter 2006, there were 241 new CRC cases, 648 cancer-related deaths, and 2361 all-cause deaths identified. Overall, the associations between BMI change and CRC incidence and cancer-related mortality, respectively, were not statistically significant. Compared with participants whose BMI were stable, individuals who had a decrease in BMI were at increased risk of all-cause mortality, and the HRs were 1.21 (95% CI: 1.03–1.42), 1.65 (95% CI: 1.44–1.89), 1.84 (95% CI: 1.56–2.17), and 2.84 (95% CI: 2.42–3.35) for 2.5–4.9%, 5.0–9.9%, 10.0–14.9%, and ≥ 15.0% decrease in BMI, respectively. An L-shaped association between BMI change and all-cause mortality was observed. Every 5% decrease in BMI was associated with a 27% increase in the risk of all-cause mortality (HR = 1.27, 95% CI: 1.22–1.31, p < 0.001). The results from subgroups showed similar trends.ConclusionsA decrease in BMI more than 5% shows a significantly increased risk of all-cause mortality among older individuals; but no significant association between increase in BMI and all-cause mortality. These findings emphasize the importance of body weight management in older population, and more studies are warranted to evaluate the cause-and-effect relationship between changes in BMI and cancer incidence/mortality.

Relation of Change of Body Mass Index to Long-Term Mortality After Cardiac Catheterization

Body-mass index (BMI) is a risk marker and therapeutic target in cardiovascular prevention. The effect of changes in BMI on mortality in patients with cardiovascular diseases has not been completely delineated. We aimed to assess the association between percent change in BMI, as measured 3-years after cardiac catheterization, and long-term mortality. Patients who underwent cardiac catheterization (n = 11,220; mean age 63 ± 10 years) were categorized according to BMI groups (normal-weight, 18.50 to 24.99 kg/m2; overweight, 25.00 to 29.99 kg/m2; obesity, ≥30 kg/m2). Follow-up BMI was considered the level measured closest to the timepoint of 3 years post catheterization. Percent change in BMI was calculated and its association with long-term all-cause mortality was investigated. Change in BMI of ±5% was observed in 46% of the patients, a decrease >5% in 15.5%, and an increase of >5% of BMI in 38.5%. Compared with those with the lowest change in BMI (±5%), the adjusted hazard ratios for mortality were 1.45 (95% confidence interval [CI], 1.27 to 1.65), and 1.69 (1.46 to 1.95) in patients with 5% to 10% and >10% decrease in BMI, respectively, and 1.05 (0.94 to 1.17), 1.15 (1.03 to 1.28), and 1.40 (1.19 to 1.64) in patients with 5% to 10%, 10% to 20% and >20% increase in BMI, respectively. The pattern was similar in normal-weight, overweight, and obese subgroups at baseline. However, the magnitude of the association with decrease BMI was more pronounced in normal-weight patients (P-for-interaction 0.031). In conclusion, the association of percent changes in BMI after cardiac catheterization and all-cause mortality had a reversed J-shaped pattern, with both weight loss and weight gain being associated with increased risk. A decrease in BMI was related to higher mortality rates than was an increase in BMI for a comparable degree of percent change.

Body mass index is associated with cortical thinning with different patterns in mid- and late-life.

High BMI at midlife is associated with increased risk of dementia as well as faster decline in cognitive function. In late-life, however, high BMI has been found to be associated with both increased and decreased dementia risk. The objective of this study was to investigate the neural substrates of this age-related change in body mass index (BMI) risk. We measured longitudinal cortical thinning over the whole brain, based on magnetic resonance imaging scans for 910 individuals aged 44-66 years at baseline. Subjects were sampled from a large population study (PATH, Personality and Total Health through Life). After attrition and exclusions, the final analysis was based on 792 individuals, including 387 individuals aged 60-66 years and 405 individuals aged 44-49 years. A mixed-effects model was used to test the association between cortical thinning and baseline BMI, as well as percentage change in BMI. Increasing BMI was associated with increased cortical thinning in posterior cingulate at midlife (0.014 mm kg-1 m-2, confidence interval; CI=0.005, 0.023, P<0.05 false discovery rate (FDR) corrected). In late-life, increasing BMI was associated with reduced cortical thickness, most prominently in the right supramarginal cortex (0.010 mm kg-1 m-2, CI=0.005-0.016, P<0.05 FDR corrected), as well as frontal regions. In late-life, decreasing BMI was also associated with increased cortical thinning, including right caudal middle frontal cortex (0.014 mm kg-1 m-2 (CI=0.006-0.023, P<0.05 FDR corrected). The pattern of cortical thinning-in association with increasing BMI at both midlife and late-life-is consistent with known obesity-related dementia risk. Increased cortical thinning in association with decreasing BMI at late-life may help explain the 'obesity paradox', where high BMI in midlife appears to be a risk factor for dementia, but high BMI in late-life appears, at times, to be protective.