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      Energy intake as a short‐term biomarker for weight loss in adults with obesity receiving liraglutide: A randomized trial

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          Abstract

          Background and Objective

          Obesity is a chronic disease associated with many serious comorbidities. Pharmacologic therapies are approved for the treatment of obesity; however, short‐term biomarkers to predict weight loss are not well understood. This study aimed to determine the ability of single‐meal energy intake (EI) to predict weight loss in participants with obesity treated with liraglutide.

          Methods

          In this randomized, double‐blind, placebo‐controlled study, participants received subcutaneous liraglutide (titrated to 3.0 mg/day) or placebo once daily, with inpatient assessments at baseline and weeks 3 and 6. The primary endpoint was change from baseline (CFB) in EI during consecutive ad libitum lunch meals at weeks 3 and 6. Secondary endpoints included CFB in 24‐ and 48‐h EI, weight, appetite scores, and gastric emptying measures.

          Results

          Sixty‐one participants were randomized ( n = 32, liraglutide; n = 29, placebo). The least squares mean (LSM) difference (95% CI; p‐value) in CFB in EI during ad libitum lunch meals between the liraglutide and placebo groups was −236 (−322, −149; p < 0.0001) kcal at week 3 and –244 (−339, −148, p < 0.0001) kcal at week 6. The liraglutide group experienced significant weight loss at weeks 3 and 6, compared with placebo. Weight loss was significantly correlated with EI, but not with appetite score or gastric emptying.

          Conclusions

          EI during a single meal is a robust clinical predictor of weight changes in participants with obesity. Future clinical trials can utilize EI at a single meal as a predictor of weight loss.

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          Most cited references18

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          The physiology of glucagon-like peptide 1.

          Glucagon-like peptide 1 (GLP-1) is a 30-amino acid peptide hormone produced in the intestinal epithelial endocrine L-cells by differential processing of proglucagon, the gene which is expressed in these cells. The current knowledge regarding regulation of proglucagon gene expression in the gut and in the brain and mechanisms responsible for the posttranslational processing are reviewed. GLP-1 is released in response to meal intake, and the stimuli and molecular mechanisms involved are discussed. GLP-1 is extremely rapidly metabolized and inactivated by the enzyme dipeptidyl peptidase IV even before the hormone has left the gut, raising the possibility that the actions of GLP-1 are transmitted via sensory neurons in the intestine and the liver expressing the GLP-1 receptor. Because of this, it is important to distinguish between measurements of the intact hormone (responsible for endocrine actions) or the sum of the intact hormone and its metabolites, reflecting the total L-cell secretion and therefore also the possible neural actions. The main actions of GLP-1 are to stimulate insulin secretion (i.e., to act as an incretin hormone) and to inhibit glucagon secretion, thereby contributing to limit postprandial glucose excursions. It also inhibits gastrointestinal motility and secretion and thus acts as an enterogastrone and part of the "ileal brake" mechanism. GLP-1 also appears to be a physiological regulator of appetite and food intake. Because of these actions, GLP-1 or GLP-1 receptor agonists are currently being evaluated for the therapy of type 2 diabetes. Decreased secretion of GLP-1 may contribute to the development of obesity, and exaggerated secretion may be responsible for postprandial reactive hypoglycemia.
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            Glucagon-like peptide-1 7-36: a physiological incretin in man.

            The physiological role of glucagon-like peptide-1 7-36 amide (GLP-1 7-36) in man was investigated. GLP-1 7-36-like immunoreactivity was found in the human bowel; its circulating level rose after oral glucose and after a test breakfast. When it was infused into seven volunteers at a rate to mimic its postprandial plasma concentration in the fasting state, plasma insulin levels rose significantly and glucose and glucagon concentrations fell. During an intravenous glucose load, it greatly enhanced insulin release and significantly reduced peak plasma glucose concentrations, compared with a control saline infusion, even inducing postinfusion reactive hypoglycaemia. By comparison, infusion of glucose-dependent insulinotropic peptide (GIP) to physiological levels was less effective in stimulating insulin release. These observations suggest that GLP-1 7-36 is a physiological incretin and that it is more powerful than GIP. The observation of greatly increased postprandial plasma GLP-1 7-36 levels in patients with postgastrectomy dumping syndrome suggests that it may mediate the hyperinsulinaemia and reactive hypoglycaemia of this disorder.
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              A two-year randomized trial of obesity treatment in primary care practice.

              Calls for primary care providers (PCPs) to offer obese patients behavioral weight-loss counseling have not been accompanied by adequate guidance on how such care could be delivered. This randomized trial compared weight loss during a 2-year period in response to three lifestyle interventions, all delivered by PCPs in collaboration with auxiliary health professionals (lifestyle coaches) in their practices. We randomly assigned 390 obese adults in six primary care practices to one of three types of intervention: usual care, consisting of quarterly PCP visits that included education about weight management; brief lifestyle counseling, consisting of quarterly PCP visits combined with brief monthly sessions with lifestyle coaches who instructed participants about behavioral weight control; or enhanced brief lifestyle counseling, which provided the same care as described for the previous intervention but included meal replacements or weight-loss medication (orlistat or sibutramine), chosen by the participants in consultation with the PCPs, to potentially increase weight loss. Of the 390 participants, 86% completed the 2-year trial, at which time, the mean (±SE) weight loss with usual care, brief lifestyle counseling, and enhanced brief lifestyle counseling was 1.7±0.7, 2.9±0.7, and 4.6±0.7 kg, respectively. Initial weight decreased at least 5% in 21.5%, 26.0%, and 34.9% of the participants in the three groups, respectively. Enhanced lifestyle counseling was superior to usual care on both these measures of success (P=0.003 and P=0.02, respectively), with no other significant differences among the groups. The benefits of enhanced lifestyle counseling remained even after participants given sibutramine were excluded from the analyses. There were no significant differences between the intervention groups in the occurrence of serious adverse events. Enhanced weight-loss counseling helps about one third of obese patients achieve long-term, clinically meaningful weight loss. (Funded by the National Heart, Lung, and Blood Institute; POWER-UP ClinicalTrials.gov number, NCT00826774.).
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                Author and article information

                Contributors
                aditi.saxena@pfizer.com
                Journal
                Obes Sci Pract
                Obes Sci Pract
                10.1002/(ISSN)2055-2238
                OSP4
                Obesity Science & Practice
                John Wiley and Sons Inc. (Hoboken )
                2055-2238
                09 March 2021
                June 2021
                : 7
                : 3 ( doiID: 10.1002/osp4.v7.3 )
                : 281-290
                Affiliations
                [ 1 ] Worldwide Research and Development Pfizer Inc Cambridge Massachusetts USA
                [ 2 ] AdventHealth Translational Research Institute Orlando Florida USA
                Author notes
                [*] [* ] Correspondence

                Aditi R. Saxena, Pfizer Inc, 1 Portland Street Cambridge, MA 02139, USA.

                Email: aditi.saxena@ 123456pfizer.com

                Article
                OSP4486
                10.1002/osp4.486
                8170575
                34123395
                84fbedae-741a-4767-8de6-b02aa6dbf214
                © 2021 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 23 December 2020
                : 17 July 2020
                : 23 January 2021
                Page count
                Figures: 7, Tables: 2, Pages: 10, Words: 6327
                Funding
                Funded by: Pfizer Inc
                Categories
                Original Article
                Original Article
                Custom metadata
                2.0
                June 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.2 mode:remove_FC converted:02.06.2021

                energy intake,glucagon‐like peptide‐1,obesity,weight loss

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