Exenatide has a pronounced effect on energy intake but not energy expenditure in non-diabetic subjects with obesity: A randomized, double-blind, placebo-controlled trial

Basolo, Alessio; Burkholder, Joshua; Osgood, Kristy; Graham, Alexis; Bundrick, Sarah C.; Frankl, J; Piaggi, Paolo; Thearle, Marie S.; Krakoff, Jonathan

doi:10.1016/j.metabol.2018.03.017

Cited by 30 publications

(25 citation statements)

References 46 publications

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“…The impressive weight loss observed with several peptides in mice often reflects contributions from sympathetic nervous system engagement, BAT activation, and induction of energy expenditure, metabolic events that have rarely been recapitulated in sustained human studies. For example, GLP-1 increases sympathetic nervous system activity [ 115 ] and energy expenditure in animal experiments [ 116 , 117 ], but not in humans with T2D or obesity [ [118] , [119] , [120] , [121] , [122] ]. Similar findings relate to glucagon-containing agonists that robustly activate BAT and energy expenditure in mice [ 46 , 48 , 50 ], yet these mechanisms have not made appreciable contributions to weight loss in human studies.…”

Section: Pitfalls and Data Limitationsmentioning

confidence: 99%

Glucagon-like peptide-1 receptor co-agonists for treating metabolic disease

Baggio

Drucker

2021

Molecular Metabolism

195

122

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Background Glucagon-like peptide-1 receptor (GLP-1R) agonists are approved to treat type 2 diabetes and obesity. They elicit robust improvements in glycemic control and weight loss, combined with cardioprotection in individuals at risk of or with pre-existing cardiovascular disease. These attributes make GLP-1 a preferred partner for next-generation therapies exhibiting improved efficacy yet retaining safety to treat diabetes, obesity, non-alcoholic steatohepatitis, and related cardiometabolic disorders. The available clinical data demonstrate that the best GLP-1R agonists are not yet competitive with bariatric surgery, emphasizing the need to further improve the efficacy of current medical therapy. Scope of review In this article, we discuss data highlighting the physiological and pharmacological attributes of potential peptide and non-peptide partners, exemplified by amylin, glucose-dependent insulinotropic polypeptide (GIP), and steroid hormones. We review the progress, limitations, and future considerations for translating findings from preclinical experiments to competitive efficacy and safety in humans with type 2 diabetes and obesity. Major conclusions Multiple co-agonist combinations exhibit promising clinical efficacy, notably tirzepatide and investigational amylin combinations. Simultaneously, increasing doses of GLP-1R agonists such as semaglutide produces substantial weight loss, raising the bar for the development of new unimolecular co-agonists. Collectively, the available data suggest that new co-agonists with robust efficacy should prove superior to GLP-1R agonists alone to treat metabolic disorders.

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Section: Pitfalls and Data Limitationsmentioning

confidence: 99%

Glucagon-like peptide-1 receptor co-agonists for treating metabolic disease

Baggio

Drucker

2021

Molecular Metabolism

195

122

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“…related to albumin's ability to binds a host of substances including hormones known to alter appetite (e.g. thyroxine, glucocorticoids) (31)(32)(33). Albumin may serves as a carrierligand for these substances providing transport to sites of action, metabolism, and excretion (34).…”

Section: A B D Cmentioning

confidence: 99%

Reduced Albumin Concentration Predicts Weight Gain and Higher Ad Libitum Energy Intake in Humans

Basolo¹,

Ando²,

Chang³

et al. 2021

Front. Endocrinol.

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ObjectiveCirculating albumin is negatively associated with adiposity but whether it is associated with increased energy intake, lower energy expenditure or weight gain has not been examined.MethodsIn study 1 (n=238; 146 men), we evaluated whether fasting albumin concentration was associated with 24-h energy expenditure and ad libitum energy intake. In study 2 (n=325;167 men), we evaluated the association between plasma albumin and change in weight and body composition.ResultsAfter adjustment for known determinants of energy intake lower plasma albumin concentration was associated with greater total daily energy intake (β= 89.8 kcal/day per 0.1 g/dl difference in plasma albumin, p=0.0047). No associations were observed between plasma albumin concentrations and 24-h energy expenditure or 24-h respiratory quotient (p>0.2). Over 6 years, volunteers gained on average 7.5 ± 11.7 kg (p<0.0001). Lower albumin concentrations were associated with greater weight [β=3.53 kg, p=0.039 (adjusted for age, sex, follow up time), CI 0.16 to 6.21 per 1 g/dl difference albumin concentration] and fat mass (β=2.3 kg, p=0.022), respectively, but not with changes in fat free mass (p=0.06).ConclusionsLower albumin concentrations were associated with increased ad libitum food intake and weight gain, indicating albumin as a marker of energy intake regulation.Clinical Trial RegistrationClinicalTrials.gov, identifiers NCT00340132, NCT00342732.

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“…Previous studies have demonstrated an effect of GLP-1 receptor agonists on energy intake [10,20] through both central and peripheral mechanisms in rats and humans [21,22]. Our findings that GLP-1 was negatively associated with carbohydrate and LF/HSS intake and not total energy intake indicates a possible different mechanism by which GLP-1 regulates intake and may be explained by the potential role of GLP-1 in food reward and satiety.…”

Section: Discussionmentioning

confidence: 54%

Fasting glucagon-like peptide 1 concentration is associated with lower carbohydrate intake and increases with overeating

Basolo

Heinitz

Stinson

et al. 2018

J Endocrinol Invest

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Purpose-Glucagon-like peptide 1 (GLP-1) is an incretin hormone that appears to play a major role in the control of food intake. The aim of this investigation was to evaluate and quantify the association of circulating GLP-1 concentration with ad libitum total calorie and macronutrient intake.Methods-One-hundred fifteen individuals (72 men) aged 35 ± 10 years were admitted for an inpatient study investigating the determinants of energy intake. Ad libitum food intake was assessed during 3 days using a reproducible vending machine paradigm. Fasting plasma GLP-1 concentrations were measured on the morning of the first day and on the morning of the fourth day after ad libitum feeding.Results-Plasma GLP-1 concentrations increased by 14% after 3 days of ad libitum food intake. Individuals overate on average 139 ± 45% of weight-maintaining energy needs. Fasting plasma GLP-1 on day 1 was negatively associated with carbohydrate intake (r=−0.2, p=0.03) and with daily energy intake from low fat-high simple sugar (r=−0.22, p=0.016). Conclusion-Higher plasma GLP-1 concentrations prior to ad libitum food intake were associated with lower carbohydrate intake and lower simple sugar ingestion, indicating a possible role of the GLP-1 in the reward pathway regulating simple sugar intake.

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Exenatide has a pronounced effect on energy intake but not energy expenditure in non-diabetic subjects with obesity: A randomized, double-blind, placebo-controlled trial

Cited by 30 publications

References 46 publications

Glucagon-like peptide-1 receptor co-agonists for treating metabolic disease

Glucagon-like peptide-1 receptor co-agonists for treating metabolic disease

Reduced Albumin Concentration Predicts Weight Gain and Higher Ad Libitum Energy Intake in Humans

Fasting glucagon-like peptide 1 concentration is associated with lower carbohydrate intake and increases with overeating

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