Effect of the once-daily human GLP-1 analogue liraglutide on appetite, energy intake, energy expenditure and gastric emptying in type 2 diabetes

Horowitz, Michael; Flint, Anne; Jones, Karen L.; Hindsberger, Charlotte; Rasmussen, Maria; Kapitza, Christoph; Doran, Selena; Jax, Thomas; Zdravković, Milan; Chapman, Ian

doi:10.1016/j.diabres.2012.02.016

Cited by 142 publications

(133 citation statements)

References 45 publications

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“…The effect on energy intake is consistent with previous data from non‐clinical37 and clinical studies with other GLP‐1RAs,38, 39 as well as studies with native GLP‐1,3 with the reduction in energy intake correlating with reduction in body weight 3, 38, 39. However, the effects with semaglutide appear to be greater than those of other GLP‐1RAs, consistent with larger weight reductions observed in larger semaglutide trials of longer duration;40 however, caution is required when drawing an indirect comparison between trials.…”

Section: Discussionsupporting

confidence: 90%

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

Blundell

Finlayson

Axelsen

et al. 2017

Diabetes Obesity Metabolism

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340

370

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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.

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Section: Discussionsupporting

confidence: 90%

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

Blundell

Finlayson

Axelsen

et al. 2017

Diabetes Obesity Metabolism

Self Cite

340

370

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“…During acute GLP-1 infusion, energy expenditure caused by diet-induced thermogenesis was decreased in both healthy lean and obese individuals (Flint et al 2000. After treatment of 4 weeks with liraglutide in T2DM patients, the estimated 24 h resting energy expenditure tended to increase (Horowitz et al 2012), but this effect was not confirmed in trials with a treatment duration of 8-10 weeks with liraglutide or exenatide (Harder et al 2004, Bradley et al 2012.…”

Section: Effects Of Glp-1 and Glp-1ra On Energy Balancementioning

confidence: 81%

Effects of glucagon-like peptide 1 on appetite and body weight: focus on the CNS

Bloemendaal¹,

Kulve²,

Fleur

et al. 2013

Journal of Endocrinology

220

176

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The delivery of nutrients to the gastrointestinal tract after food ingestion activates the secretion of several gut-derived mediators, including the incretin hormone glucagon-like peptide 1 (GLP-1). GLP-1 receptor agonists (GLP-1RA), such as exenatide and liraglutide, are currently employed successfully in the treatment of patients with type 2 diabetes mellitus. GLP-1RA improve glycaemic control and stimulate satiety, leading to reductions in food intake and body weight. Besides gastric distension and peripheral vagal nerve activation, GLP-1RA induce satiety by influencing brain regions involved in the regulation of feeding, and several routes of action have been proposed. This review summarises the evidence for a physiological role of GLP-1 in the central regulation of feeding behaviour and the different routes of action involved. Also, we provide an overview of presently available data on pharmacological stimulation of GLP-1 pathways leading to alterations in CNS activity, reductions in food intake and weight loss.

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“…GE in healthy individuals exhibits a wide interindividual variation of~4-17 kJ/min (~1-4 kcal/min) [14]; this is increased in diabetes because of the high prevalence of delayed [15], and occasionally rapid, GE [16]. The reduction in postprandial glucose following acute administration of GLP-1 [17][18][19] or 'short-acting' GLP-1 agonists [20,21] relates primarily to slowing of GE but clinical studies relating to the effects of GLP-1 and its agonists on BP have not discriminated between effects on fasting vs postprandial BP.…”

Section: Introductionmentioning

confidence: 99%

Effects of exogenous glucagon-like peptide-1 on blood pressure, heart rate, gastric emptying, mesenteric blood flow and glycaemic responses to oral glucose in older individuals with normal glucose tolerance or type 2 diabetes

et al. 2015

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Aims/hypothesis A postprandial fall in BP occurs frequently in older individuals and in patients with type 2 diabetes. The magnitude of this decrease in BP is related to the rate of gastric emptying (GE). Intravenous administration of glucagon-like peptide-1 (GLP-1) attenuates the hypotensive response to intraduodenal glucose in healthy older individuals. We sought to determine the effects of exogenous GLP-1 on BP, GE, superior mesenteric artery (SMA) flow and glycaemic response to oral ingestion of glucose in healthy older individuals and patients with type 2 diabetes. Methods Fourteen older volunteers (six men, eight women; age 72.1±1.1 years) and ten patients with type 2 diabetes (six men, four women; age 68.7±3.4 years; HbA 1c 6.6±0.2% [48.5± 2.0 mmol/mol]; nine with blood glucose managed with metformin, two with a sulfonylurea and one with a dipeptidyl-peptidase 4 inhibitor) received an i.v. infusion of GLP-1 (0.9 pmol kg −1 min −1 ) or saline (154 mmol/l NaCl) for 150 min (t=−30 min to t= 120 min) in randomised order. At t=0 min, volunteers consumed a radiolabelled 75 g glucose drink. BP was assessed with an automated device, GE by scintigraphy and SMA flow by ultrasonography. Blood glucose and serum insulin were measured. Results GLP-1 attenuated the fall in diastolic BP after the glucose drink in older individuals (p<0.05) and attenuated the fall in systolic and diastolic BP in patients with type 2 diabetes (p<0.05). GE was faster in patients with type 2 diabetes than in healthy individuals (p<0.05). In both groups, individuals had slower GE (p<0.001), decreased SMA flow (p<0.05) and a lower degree of glycaemia (p<0.001) when receiving GLP-1. Conclusions/interpretation Intravenous GLP-1 attenuates the hypotensive response to orally administered glucose and decreases SMA flow, probably by slowing GE. GLP-1 and 'short-acting' GLP-1 agonists may be useful in the management of postprandial hypotension.

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Effect of the once-daily human GLP-1 analogue liraglutide on appetite, energy intake, energy expenditure and gastric emptying in type 2 diabetes

Cited by 142 publications

References 45 publications

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

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

Effects of glucagon-like peptide 1 on appetite and body weight: focus on the CNS

Effects of exogenous glucagon-like peptide-1 on blood pressure, heart rate, gastric emptying, mesenteric blood flow and glycaemic responses to oral glucose in older individuals with normal glucose tolerance or type 2 diabetes

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