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

Abstract

AimThe aim of this trial was to investigate the mechanism of action for body weight loss with semaglutide.Materials and methodsThis 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.ResultsAfter 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.ConclusionAfter 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.

Semaglutide improves postprandial glucose and lipid metabolism, and delays first‐hour gastric emptying in subjects with obesity

“…Previously, we reported that semaglutide, compared with placebo, reduced body weight and ad libitum energy intake after 12 weeks of treatment . This finding was supported by different aspects of homeostatic and hedonic appetite parameters .…”

The Clinical Impact of GLP-1 Receptor Agonists in Type 2 Diabetes: Focus on the Long-Acting Analogs

“…Ongoing research and development can be expected to clarify the effectiveness and safety of the implantable osmotic pump for administration of exenatide or other relatively rapidly cleared analogs, the potential clinical utility of an oral preparation of semaglutide, 67 and the effectiveness of GLP-1 RAs for management of obesity 57,68 and of nonalcoholic hepatosteatosis. 69 …”

Anti-Obesity Therapy: from Rainbow Pills to Polyagonists

“…These medicines include exenatide (Byetta; AstraZeneca, Cambridge, UK), lixisenatide (Lyxumia; Sanofi, Paris, France), liraglutide (Victoza; Novo Nordisk, Copenhagen, Denmark), dulaglutide (Trulicity; Eli Lilly & Co., Indianapolis, IN), and albiglutide (Tanzeum; GlaskoSmithKline, Middlesex, UK). Semaglutide (Novo Nordisk, Copenhagen, Denmark) is a late-stage, longacting structural refinement related to liraglutide that when coformulated with suitable absorption enhancers is reported to be active in oral application (Gotfredsen et al, 2014;Finan et al, 2015a;Kapitza et al, 2015;Ahren et al, 2017;Blundell et al, 2017).…”