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      Effects of once‐weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity

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          Abstract

          Aim

          The aim of this trial was to investigate the mechanism of action for body weight loss with semaglutide.

          Materials and methods

          This randomised, double‐blind, placebo‐controlled, two‐period crossover trial investigated the effects of 12 weeks of treatment with once‐weekly subcutaneous semaglutide, dose‐escalated to 1.0 mg, in 30 subjects with obesity. Ad libitum energy intake, ratings of appetite, thirst, nausea and well‐being, control of eating, food preference, resting metabolic rate, body weight and body composition were assessed.

          Results

          After a standardised breakfast, semaglutide, compared with placebo, led to a lower ad libitum energy intake during lunch (−1255  kJ; P  < .0001) and during the subsequent evening meal ( P  = .0401) and snacks ( P  = .0034), resulting in a 24% reduction in total energy intake across all ad libitum meals throughout the day (−3036  kJ; P  < .0001). Fasting overall appetite suppression scores were improved with semaglutide vs placebo, while nausea ratings were similar. Semaglutide was associated with less hunger and food cravings, better control of eating and a lower preference for high‐fat foods. Resting metabolic rate, adjusted for lean body mass, did not differ between treatments. Semaglutide led to a reduction from baseline in mean body weight of 5.0 kg, predominantly from body fat mass.

          Conclusion

          After 12 weeks of treatment, ad libitum energy intake was substantially lower with semaglutide vs placebo with a corresponding loss of body weight observed with semaglutide. In addition to reduced energy intake, likely mechanisms for semaglutide‐induced weight loss included less appetite and food cravings, better control of eating and lower relative preference for fatty, energy‐dense foods.

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          Most cited references27

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          Efficacy and Safety Comparison of Liraglutide, Glimepiride, and Placebo, All in Combination With Metformin, in Type 2 Diabetes

          OBJECTIVE—The efficacy and safety of adding liraglutide (a glucagon-like peptide-1 receptor agonist) to metformin were compared with addition of placebo or glimepiride to metformin in subjects previously treated with oral antidiabetes (OAD) therapy. RESEARCH DESIGN AND METHODS—In this 26-week, double-blind, double-dummy, placebo- and active-controlled, parallel-group trial, 1,091 subjects were randomly assigned (2:2:2:1:2) to once-daily liraglutide (either 0.6, 1.2, or 1.8 mg/day injected subcutaneously), to placebo, or to glimepiride (4 mg once daily). All treatments were in combination therapy with metformin (1g twice daily). Enrolled subjects (aged 25–79 years) had type 2 diabetes, A1C of 7–11% (previous OAD monotherapy for ≥3 months) or 7–10% (previous OAD combination therapy for ≥3 months), and BMI ≤40 kg/m2. RESULTS—A1C values were significantly reduced in all liraglutide groups versus the placebo group (P < 0.0001) with mean decreases of 1.0% for 1.8 mg liraglutide, 1.2 mg liraglutide, and glimepiride and 0.7% for 0.6 mg liraglutide and an increase of 0.1% for placebo. Body weight decreased in all liraglutide groups (1.8–2.8 kg) compared with an increase in the glimepiride group (1.0 kg; P < 0.0001). The incidence of minor hypoglycemia with liraglutide (∼3%) was comparable to that with placebo but less than that with glimepiride (17%; P < 0.001). Nausea was reported by 11–19% of the liraglutide-treated subjects versus 3–4% in the placebo and glimepiride groups. The incidence of nausea declined over time. CONCLUSIONS—In subjects with type 2 diabetes, once-daily liraglutide induced similar glycemic control, reduced body weight, and lowered the occurrence of hypoglycemia compared with glimepiride, when both had background therapy of metformin.
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            Reproducibility, power and validity of visual analogue scales in assessment of appetite sensations in single test meal studies.

            To examine reproducibility and validity of visual analogue scales (VAS) for measurement of appetite sensations, with and without a diet standardization prior to the test days. On two different test days the subjects recorded their appetite sensations before breakfast and every 30 min during the 4.5 h postprandial period under exactly the same conditions. 55 healthy men (age 25.6+/-0.6 y, BMI 22.6+/-0.3 kg¿m2). VAS were used to record hunger, satiety, fullness, prospective food consumption, desire to eat something fatty, salty, sweet or savoury, and palatability of the meals. Subsequently an ad libitum lunch was served and energy intake was recorded. Reproducibility was assessed by the coefficient of repeatability (CR) of fasting, mean 4.5 h and peak/nadir values. CRs (range 20-61 mm) were larger for fasting and peak/nadir values compared with mean 4.5 h values. No parameter seemed to be improved by diet standardization. Using a paired design and a study power of 0.8, a difference of 10 mm on fasting and 5 mm on mean 4.5 h ratings can be detected with 18 subjects. When using desires to eat specific types of food or an unpaired design, more subjects are needed due to considerable variation. The best correlations of validity were found between 4.5 h mean VAS of the appetite parameters and subsequent energy intake (r=+/-0.50-0.53, P<0.001). VAS scores are reliable for appetite research and do not seem to be influenced by prior diet standardization. However, consideration should be given to the specific parameters being measured, their sensitivity and study power. International Journal of Obesity (2000)24, 38-48
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              Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults

              Introduction: Mechanisms for liraglutide-induced weight loss are poorly understood. Objective: We investigated the effects of liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese non-diabetic individuals. Design: Participants (N=49, 18–75 years, body mass index: 30–40 kg m−2) were randomized to two of three treatments: liraglutide 1.8 mg, 3.0 mg, or placebo in a double-blind, incomplete crossover trial. After 5 weeks, 24-h energy expenditure (EE) and substrate oxidation were measured in a respiratory chamber. Gastric emptying (acetaminophen absorption method), glycemic parameters and appetite were assessed during a 5-h meal test. Ad libitum energy intake during a subsequent lunch was also assessed. Results: Five-hour gastric emptying (AUC0–300 min) was found to be equivalent for liraglutide 1.8 versus 3.0 mg (primary end point), and for both liraglutide doses versus placebo, as 90% confidence intervals for the estimated treatment ratios were contained within the prespecified interval (0.80–1.25). However, 1-h gastric emptying was 23% lower than placebo with liraglutide 3.0 mg (P=0.007), and a nonsignificant 13% lower than placebo with liraglutide 1.8 mg (P=0.14). Both liraglutide doses similarly reduced fasting glucose (0.5–0.6 mmol l−1 versus placebo, P<0.0001), glucose Cmax and 1-h AUC versus placebo; only liraglutide 3.0 mg reduced iAUC0–300 min (by ∼26% versus placebo, P=0.02). Glucagon iAUC0–300 min decreased by ∼30%, and iAUC0–60 min for insulin and C-peptide was ∼20% lower with both liraglutide doses versus placebo. Liraglutide doses similarly increased mean postprandial satiety and fullness ratings, reduced hunger and prospective food consumption and decreased ad libitum energy intake by ∼16%. Liraglutide-associated reductions in EE were partly explained by a decrease in body weight. A relative shift toward increased fat and reduced carbohydrate oxidation was observed with liraglutide. Clinicaltrials.gov ID:NCT00978393. Funding: Novo Nordisk. Conclusion: Gastric emptying AUC0–300 min was equivalent for liraglutide 1.8 and 3.0 mg, and for liraglutide versus placebo, whereas reductions in 1-h gastric emptying of 23% with liraglutide 3.0 mg and 13% with 1.8 mg versus placebo were observed. Liraglutide 3.0 mg improved postprandial glycemia to a greater extent than liraglutide 1.8 mg. Liraglutide-induced weight loss appears to be mediated by reduced appetite and energy intake rather than increased EE.
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                Author and article information

                Contributors
                j.e.blundell@leeds.ac.uk
                Journal
                Diabetes Obes Metab
                Diabetes Obes Metab
                10.1111/(ISSN)1463-1326
                DOM
                Diabetes, Obesity & Metabolism
                Blackwell Publishing Ltd (Oxford, UK )
                1462-8902
                1463-1326
                05 May 2017
                September 2017
                : 19
                : 9 ( doiID: 10.1111/dom.2017.19.issue-9 )
                : 1242-1251
                Affiliations
                [ 1 ] Department of Psychology University of Leeds Leeds UK
                [ 2 ] Novo Nordisk Søborg Denmark
                Author notes
                [*] [* ] Correspondence John Blundell, Chair in PsychoBiology, Department of Psychology, Faculty of Medicine and Health, University of Leeds, Leeds LS2 9JT, UK. Email: j.e.blundell@ 123456leeds.ac.uk
                Author information
                http://orcid.org/0000-0002-7085-9596
                Article
                DOM12932
                10.1111/dom.12932
                5573908
                28266779
                ea9e3f57-68a6-405e-bb3b-9055d574f58f
                © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 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
                : 06 December 2016
                : 27 February 2017
                : 01 March 2017
                Page count
                Figures: 4, Tables: 1, Pages: 1, Words: 6048
                Funding
                Funded by: Novo Nordisk A/S, Søborg, Denmark
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                dom12932
                dom12932-hdr-0001
                September 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.1.8 mode:remove_FC converted:29.08.2017

                Endocrinology & Diabetes
                body composition,energy regulation,glp‐1 analogue,glucagon‐like peptide‐1,randomised trial,semaglutide,type 2 diabetes,visual analogue scale

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