IMPORTANCE: The effect of continuing vs withdrawing treatment with semaglutide, a glucagon-like peptide 1 receptor agonist, on weight loss maintenance in people with overweight or obesity is unknown. ...OBJECTIVE: To compare continued once-weekly treatment with subcutaneous semaglutide, 2.4 mg, with switch to placebo for weight maintenance (both with lifestyle intervention) in adults with overweight or obesity after a 20-week run-in with subcutaneous semaglutide titrated to 2.4 mg weekly. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, 68-week phase 3a withdrawal study conducted at 73 sites in 10 countries from June 2018 to March 2020 in adults with body mass index of at least 30 (or ≥27 with ≥1 weight-related comorbidity) and without diabetes. INTERVENTIONS: A total of 902 participants received once-weekly subcutaneous semaglutide during run-in. After 20 weeks (16 weeks of dose escalation; 4 weeks of maintenance dose), 803 participants (89.0%) who reached the 2.4-mg/wk semaglutide maintenance dose were randomized (2:1) to 48 weeks of continued subcutaneous semaglutide (n = 535) or switched to placebo (n = 268), plus lifestyle intervention in both groups. MAIN OUTCOMES AND MEASURES: The primary end point was percent change in body weight from week 20 to week 68; confirmatory secondary end points were changes in waist circumference, systolic blood pressure, and physical functioning (assessed using the Short Form 36 Version 2 Health Survey, Acute Version SF-36). RESULTS: Among 803 study participants who completed the 20-week run-in period (with a mean weight loss of 10.6%) and were randomized (mean age, 46 SD, 12 years; 634 79% women; mean body weight, 107.2 kg SD, 22.7 kg), 787 participants (98.0%) completed the trial and 741 (92.3%) completed treatment. With continued semaglutide, mean body weight change from week 20 to week 68 was −7.9% vs +6.9% with the switch to placebo (difference, −14.8 95% CI, −16.0 to −13.5 percentage points; P < .001). Waist circumference (−9.7 cm 95% CI, −10.9 to −8.5 cm), systolic blood pressure (−3.9 mm Hg 95% CI, −5.8 to −2.0 mm Hg), and SF-36 physical functioning score (2.5 95% CI, 1.6-3.3) also improved with continued subcutaneous semaglutide vs placebo (all P < .001). Gastrointestinal events were reported in 41.9% of participants who continued subcutaneous semaglutide vs 26.1% with placebo; similar proportions discontinued treatment because of adverse events with continued semaglutide (2.4%) and placebo (2.2%). CONCLUSIONS AND RELEVANCE: Among adults with overweight or obesity who completed a 20-week run-in period with subcutaneous semaglutide, 2.4 mg once weekly, maintaining treatment with semaglutide compared with switching to placebo resulted in continued weight loss over the following 48 weeks. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03548987
Growth differentiation factor 15 (GDF15), a distant member of the transforming growth factor (TGF)-β family, is a secreted protein that circulates as a 25-kDa dimer. In humans, elevated GDF15 ...correlates with weight loss, and the administration of GDF15 to mice with obesity reduces body weight, at least in part, by decreasing food intake. The mechanisms through which GDF15 reduces body weight remain poorly understood, because the cognate receptor for GDF15 is unknown. Here we show that recombinant GDF15 induces weight loss in mice fed a high-fat diet and in nonhuman primates with spontaneous obesity. Furthermore, we find that GDF15 binds with high affinity to GDNF family receptor α-like (GFRAL), a distant relative of receptors for a distinct class of the TGF-β superfamily ligands. Gfral is expressed in neurons of the area postrema and nucleus of the solitary tract in mice and humans, and genetic deletion of the receptor abrogates the ability of GDF15 to decrease food intake and body weight in mice. In addition, diet-induced obesity and insulin resistance are exacerbated in GFRAL-deficient mice, suggesting a homeostatic role for this receptor in metabolism. Finally, we demonstrate that GDF15-induced cell signaling requires the interaction of GFRAL with the coreceptor RET. Our data identify GFRAL as a new regulator of body weight and as the bona fide receptor mediating the metabolic effects of GDF15, enabling a more comprehensive assessment of GDF15 as a potential pharmacotherapy for the treatment of obesity.
The existence of metabolic adaptation, following weight loss, remains a controversial issue. To our knowledge, no study has evaluated the role of energy balance (EB) in modulating metabolic ...adaptation.
The aim of this study was to determine if metabolic adaptation, at the level of resting metabolic rate (RMR), is modulated by participants’ EB status. A secondary aim was to investigate if metabolic adaptation was associated with weight regain.
Seventy-one individuals with obesity (BMI: 34.6 ± 3.4 kg/m2; age: 45.4 ± 8.2 y; 33 men) enrolled in a 1000-kcal/d diet for 8 wk, followed by 4 wk of weight stabilization and a 9-mo weight loss maintenance program. Body weight/composition and RMR were measured at baseline, week 9 (W9), week 13 (W13), and 1 y (1Y). Metabolic adaptation was defined as a significantly different (lower or higher) measured compared with predicted RMR.
Participants lost on average 14 kg by W9, followed by weight stabilization at W13, and regained 29% of their initial weight loss at 1Y. Metabolic adaptation was found at W9 (−92 ± 110 kcal/d, P < 0.001) and W13 (−38 ± 124 kcal/d, P = 0.011) but was not correlated with weight regain. A significant reduction in metabolic adaptation was seen between W9 and W13 (−53 ± 101 kcal/d, P < 0.001). In a subset of participants who gained weight between W9 and W13 (n = 33), no metabolic adaptation was seen at W13 (−26.8 ± 121.5 kcal/d, P = 0.214). In a subset of participants with data at all time points (n = 45), metabolic adaptation was present at W9 and W13 (−107 ± 102 kcal/d, P < 0.001 and −49 ± 128 kcal/d, P = 0.013) but not at 1Y (−7 ± 129, P = 0.701).
After weight loss, metabolic adaptation at the level of RMR is dependent on the EB status of the participants, being reduced to half after a period of weight stabilization. Moreover, metabolic adaptation does not predict weight regain at 1Y follow-up. These trials were registered at clinicaltrials.gov as NCT02944253 and NCT03287726.
IMPORTANCE: Sleeve gastrectomy is increasingly used in the treatment of morbid obesity, but its long-term outcome vs the standard Roux-en-Y gastric bypass procedure is unknown. OBJECTIVE: To ...determine whether there are differences between sleeve gastrectomy and Roux-en-Y gastric bypass in terms of weight loss, changes in comorbidities, increase in quality of life, and adverse events. DESIGN, SETTING, AND PARTICIPANTS: The Swiss Multicenter Bypass or Sleeve Study (SM-BOSS), a 2-group randomized trial, was conducted from January 2007 until November 2011 (last follow-up in March 2017). Of 3971 morbidly obese patients evaluated for bariatric surgery at 4 Swiss bariatric centers, 217 patients were enrolled and randomly assigned to sleeve gastrectomy or Roux-en-Y gastric bypass with a 5-year follow-up period. INTERVENTIONS: Patients were randomly assigned to undergo laparoscopic sleeve gastrectomy (n = 107) or laparoscopic Roux-en-Y gastric bypass (n = 110). MAIN OUTCOMES AND MEASURES: The primary end point was weight loss, expressed as percentage excess body mass index (BMI) loss. Exploratory end points were changes in comorbidities and adverse events. RESULTS: Among the 217 patients (mean age, 45.5 years; 72% women; mean BMI, 43.9) 205 (94.5%) completed the trial. Excess BMI loss was not significantly different at 5 years: for sleeve gastrectomy, 61.1%, vs Roux-en-Y gastric bypass, 68.3% (absolute difference, −7.18%; 95% CI, −14.30% to −0.06%; P = .22 after adjustment for multiple comparisons). Gastric reflux remission was observed more frequently after Roux-en-Y gastric bypass (60.4%) than after sleeve gastrectomy (25.0%). Gastric reflux worsened (more symptoms or increase in therapy) more often after sleeve gastrectomy (31.8%) than after Roux-en-Y gastric bypass (6.3%). The number of patients with reoperations or interventions was 16/101 (15.8%) after sleeve gastrectomy and 23/104 (22.1%) after Roux-en-Y gastric bypass. CONCLUSIONS AND RELEVANCE: Among patients with morbid obesity, there was no significant difference in excess BMI loss between laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass at 5 years of follow-up after surgery. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00356213
Background
Currently, there is no agreement on the best method to describe weight loss (WL) after bariatric surgery. The aim of this study is to evaluate short-term outcomes using percent of total ...body weight loss (%TWL).
Methods
A single-institution retrospective study of 2420 patients undergoing Roux-en-Y gastric bypass (RYGB) was performed. Suboptimal WL was defined as %TWL < 20 % at 12 months.
Results
Mean preoperative BMI was 46.8 ± 7.8 kg/m
2
. One year after surgery, patients lost an average 14.1 kg/m
2
units of body mass index (BMI), 30.0 ± 8.5 %TWL, and 68.5 ± 22.9 %EWL. At 6 and 12 months after RYGB, mean BMI and percent excess WL (%EWL) significantly improved for all baseline BMI groups (
p
< 0.01, BMI;
p
= 0.01, %EWL), whereas mean %TWL was not significantly different among baseline BMI groups (
p
= 0.9). The regression analysis between each metric outcome and preoperative BMI demonstrated that preoperative BMI did not significantly correlate with %TWL at 1 year (
r
= 0.04,
p
= 0.3). On the contrary, preoperative BMI was strongly but negatively associated with the %EWL (
r
= −0.52,
p
< 0.01) and positively associated with the BMI units lost at 1 year (
r
= 0.56,
p
< 0.01). In total, 11.3 % of subjects achieved <20 %TWL at 12 months and were considered as suboptimal WL patients.
Conclusion
The results of our study confirm that %TWL should be the metric of choice when reporting WL because it is less influenced by preoperative BMI. Eleven percent of patients failed to achieve successful WL during the in the first year after RYGB based on our definition.
IMPORTANCE: Weight loss improves cardiometabolic risk factors in people with overweight or obesity. Intensive lifestyle intervention and pharmacotherapy are the most effective noninvasive weight loss ...approaches. OBJECTIVE: To compare the effects of once-weekly subcutaneous semaglutide, 2.4 mg vs placebo for weight management as an adjunct to intensive behavioral therapy with initial low-calorie diet in adults with overweight or obesity. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, parallel-group, 68-week, phase 3a study (STEP 3) conducted at 41 sites in the US from August 2018 to April 2020 in adults without diabetes (N = 611) and with either overweight (body mass index ≥27) plus at least 1 comorbidity or obesity (body mass index ≥30). INTERVENTIONS: Participants were randomized (2:1) to semaglutide, 2.4 mg (n = 407) or placebo (n = 204), both combined with a low-calorie diet for the first 8 weeks and intensive behavioral therapy (ie, 30 counseling visits) during 68 weeks. MAIN OUTCOMES AND MEASURES: The co–primary end points were percentage change in body weight and the loss of 5% or more of baseline weight by week 68. Confirmatory secondary end points included losses of at least 10% or 15% of baseline weight. RESULTS: Of 611 randomized participants (495 women 81.0%, mean age 46 years SD, 13, body weight 105.8 kg SD, 22.9, and body mass index 38.0 SD, 6.7), 567 (92.8%) completed the trial, and 505 (82.7%) were receiving treatment at trial end. At week 68, the estimated mean body weight change from baseline was –16.0% for semaglutide vs –5.7% for placebo (difference, −10.3 percentage points 95% CI, −12.0 to −8.6; P < .001). More participants treated with semaglutide vs placebo lost at least 5% of baseline body weight (86.6% vs 47.6%, respectively; P < .001). A higher proportion of participants in the semaglutide vs placebo group achieved weight losses of at least 10% or 15% (75.3% vs 27.0% and 55.8% vs 13.2%, respectively; P < .001). Gastrointestinal adverse events were more frequent with semaglutide (82.8%) vs placebo (63.2%). Treatment was discontinued owing to these events in 3.4% of semaglutide participants vs 0% of placebo participants. CONCLUSIONS AND RELEVANCE: Among adults with overweight or obesity, once-weekly subcutaneous semaglutide compared with placebo, used as an adjunct to intensive behavioral therapy and initial low-calorie diet, resulted in significantly greater weight loss during 68 weeks. Further research is needed to assess the durability of these findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03611582
Concurrent chemo-radiotherapy (CCR) is currently the gold standard treatment for nasopharyngeal carcinoma (NPC). The objective of this retrospective study is to analyze the variations in weight ...observed in patients with nasopharyngeal cancers under concurrent chemo-radiotherapy, in order to optimize dietary care.
240 patients with nasopharyngeal cancers, treated in the Radiotherapy department at the National Oncology Institute in Rabat between January 1st, 2018 and December 30, 2021 by curative concurrent chemo-radiotherapy, using the VMAT (Volumetric Modulated Arc Therapy) technique delivering 70 Gy in 33 fractions, with chemotherapy based on cisplatin (40mg / m2 / week) with an average of 5 cures.
Variations in weight were collected at the beginning, the mid, and the end of treatment.
From the beginning to the end of treatment, it can be seen that 85% of patients lost weight (median = 6,05 kg 1,5kg- 13,6kg), according to a separate distribution: 33% had lost more than 8 kg, 56% had lost between 3 and 8 kg, and only 11% had lost less than 3 kg.
Weight loss from mid to end of treatment (median = 3, 55 kg 1 kg–8,1 kg) was greater than that from baseline to mid-treatment (median = 2,5 kg 0,5 kg–5,5kg) (P = 0.016).
For the rest of patients (15%) : 7% had kept a stable weight, and 8% gained an average of 2 to 6 kg.
Three-quarters of patients receiving concurrent chemo-radiotherapy lost weight during treatment, despite weekly adverse reaction monitoring.
Early nutrition intervention with dietary advice associated with oral nutritional supplementation is necessary in order to favorably influence the outcome of patients by limiting weight loss.
People with obesity may seek clinical, nutritional, activity, and psychosocial guidance, but recommendations they receive in clinical settings may be inadequate or lack sufficient personalization to ...be implemented into their lives. Understanding unmet information needs may enable more tailored weight guidance. We used health narratives posted in a weight loss forum to research topics of information being sought. Public posts (N=52,576) from 1/2020-1/2022 were extracted from r/LoseIt, a Reddit weight loss forum of 3.8M members. From these, 63,006 questions were extracted using a research-purpose BERT language model tested and fine-tuned on 500 hand-annotated questions. Extracted questions were clustered into distinct topics by Top2Vec and hierarchical clustering. Excluding 2 uninterpretable topics, 27 of 28 (96%) topics represented requests for personalized recommendations. Topics focused on diet (7%), exercise (7%), sensemaking (11%), how to implement a behavior change or solve a weight-loss problem (11%), tips for specific stages of weight loss (beginning, plateau) (7%), and comparing weight loss experiences (11%). Weight-loss forum users requested personalized recommendations to support sensemaking of frustrating weight loss problems and ask for help choosing and deploying behavior change. Results call for interventions customized to individuals’ weight loss stage, process, experiences, and motivations. Disclosure C.Clark: Employee; UnitedHealth Group, Stock/Shareholder; UnitedHealth Group. J.Stremmel: None. R.G.Mccoy: Consultant; Emmi. M.Jarvis: Employee; Optum Labs, UnitedHealth Group, Stock/Shareholder; Oramed Pharmaceuticals, UnitedHealth Group, Dexcom, Inc., Apple, Hologic Inc., Intuitive Surgical. J.D.Ard: Advisory Panel; Novo Nordisk, Consultant; Eli Lilly and Company, Intuitive Surgical, Regeneron, Other Relationship; Optum Labs, Weight Watchers International, Research Support; Nestlé Health Science, Boehringer Ingelheim Inc., Epitomee, KVK Tech. N.Lambert: Employee; Optum Labs.
It is currently unknown what factor(s) may promote entry into a weight loss plateau. Given intensive lifestyle interventions (ILI) for weight loss include changes in diet, we evaluated how diet ...quality impacts characteristics of a weight loss plateau. Daily weights were obtained remotely via electronic scale from 62 adults with obesity (73% female, mean age 42±11 y and BMI 37±5 kg/m2) undergoing a 24-week ILI. Periods (≥14 d) of active weight loss or plateau were identified by threshold regression modeling. Active weight loss was defined as a per day % weight change from baseline equivalent to ≥0.5 lb loss/wk and a weight loss plateau as ±0.25lbs/wk after a period of active weight loss (in which ≥3.5% weight loss was achieved). Three unannounced self-reported ASA24 dietary recalls were obtained at baseline and 3 mo. Diet quality was assessed by the healthy eating index (HEI)-2015. 53% reached a plateau after active weight loss (27% did not achieve >3.5% weight loss, 19% re-gained directly after loss). Weight loss (i.e., plateau depth) was associated with longer time to plateau (β=–10d, P<0.01). Higher baseline diet quality (total HEI) was associated with shorter time to plateau (β=–2.6d, P=0.03), but not overall depth of plateau (β=0.1%, P=0.28). Specifically, shorter time to plateau was related to lower baseline consumption of saturated fats (β=–15d, P=0.01) and greater plateau depth was related to lower baseline consumption of added sugars (β=1.3%, P=0.04). Mean diet quality improved minimally during ILI (ΔHEI 1.9±2.2). Lower baseline HEI correlated with greater improvement in diet quality at 3 mo (β=–0.5, P<0.001, N=46), but ΔHEI did not associate with any plateau characteristics (time: β=1.1d, P=0.15; depth: β=–0.1%, P=0.16, N=25). Higher diet quality upon entry into an ILI predicted a shorter duration of weight loss prior to reaching a plateau, suggesting that individuals with healthy eating patterns may derive less sustained weight loss benefit from participation in an ILI. Disclosure S.J.Melhorn: None. L.E.Sewaybricker: None. H.Gao: None. M.De leon: None. M.Webb: None. M.Lyle: None. S.J.Beatty: None. M.Kratz: Other Relationship; Nourished by Science LLC. E.Schur: None. Funding National Institutes of Health (DK089036, DK1176223, K24HL144917); University of Washington (NORC, DK035816)
Pharmacotherapy provides an option for adults with overweight and obesity to reduce their bodyweight if lifestyle modifications fail. We summarised the latest evidence for the benefits and harms of ...weight-lowering drugs.
This systematic review and network meta-analysis included searches of PubMed, Embase, and Cochrane Library (CENTRAL) from inception to March 23, 2021, for randomised controlled trials of weight-lowering drugs in adults with overweight and obesity. We performed frequentist random-effect network meta-analyses to summarise the evidence and applied the Grading of Recommendations Assessment, Development, and Evaluation frameworks to rate the certainty of evidence, calculate the absolute effects, categorise interventions, and present the findings. The study was registered with PROSPERO, CRD 42021245678.
14 605 citations were identified by our search, of which 143 eligible trials enrolled 49 810 participants. Except for levocarnitine, all drugs lowered bodyweight compared with lifestyle modification alone; all subsequent numbers refer to comparisons with lifestyle modification. High to moderate certainty evidence established phentermine-topiramate as the most effective in lowering weight (odds ratio OR of ≥5% weight reduction 8·02, 95% CI 5·24 to 12·27; mean difference MD of percentage bodyweight change -7·97, 95% CI -9·28 to -6·66) followed by GLP-1 receptor agonists (OR 6·33, 95% CI 5·00 to 8·00; MD -5·76, 95% CI -6·30 to -5·21). Naltrexone-bupropion (OR 2·69, 95% CI 2·11 to 3·43), phentermine-topiramate (2·40, 1·69 to 3·42), GLP-1 receptor agonists (2·17, 1·71 to 2·77), and orlistat (1·72, 1·44 to 2·05) were associated with increased adverse events leading to drug discontinuation. In a post-hoc analysis, semaglutide, a GLP-1 receptor agonist, showed substantially larger benefits than other drugs with a similar risk of adverse events as other drugs for both likelihood of weight loss of 5% or more (OR 9·82, 95% CI 7·09 to 13·61) and percentage bodyweight change (MD -11·41, 95% CI -12·54 to -10·27).
In adults with overweight and obesity, phentermine-topiramate and GLP-1 receptor agonists proved the best drugs in reducing weight; of the GLP-1 agonists, semaglutide might be the most effective.
1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University.
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