Development of a delayed-release nutrient for appetite control in adults with obesity and type 2 diabetes and initial clinical testing in a single dose randomized controlled trial

• Published in: Nutrition & diabetes Vol. 9; no. 1; pp. 20 - 10
• Main Authors: Beale, E., Lim, E., Yassine, H., Azen, C., Christopher, C.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15-07-2019; Nature Publishing Group
• Subjects: 692/308/153; 692/308/575; Adult; Appetite - drug effects; Appetite Regulation - drug effects; Blood Glucose; C-Peptide - blood; Clinical Nutrition; Cross-Over Studies; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Dietary Supplements; Energy Intake - drug effects; Epidemiology; Female; Gastrointestinal surgery; Glucagon-Like Peptide 1 - blood; Humans; Insulin - blood; Internal Medicine; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Obesity; Obesity - drug therapy; Peptides; Pilot Projects; Prospective Studies
• ISSN: 2044-4052; 2044-4052
• DOI: 10.1038/s41387-019-0088-7

Background and objectives
Delivery of nutrients directly to the small intestine, either via enteral feeding tube or by gastric bypass surgery, is associated with increased levels of appetite-suppressing and glucoregulatory hormones, including GLP-1, and reduced appetite. Achieving these changes non-invasively using formulated foods may be of therapeutic benefit in individuals with obesity and related comorbidities. The aim of this pilot study was to determine the effect of a single dose of a novel delayed-release nutrient (DRN) on glucose, GLP-1, c-peptide, insulin, and appetite in adults with obesity and type 2 diabetes.
Subjects and methods
We formulated an all-natural, generally recognized as safe (‘GRAS”) DRN and conducted a randomized prospective crossover trial. Nineteen adults with obesity and type 2 diabetes underwent paired 3-h meal tolerance tests (MTT) in randomized order 1–4 weeks apart. Subjects ingested a single dose of DRN and the same nutrients as unformulated powders (UN).
Results
For DRN compared with UN, the maximal concentration (Cmax) was significantly lower for glucose, c-peptide, and insulin, and the time of maximal concentration (Tmax) was significantly delayed. While Tmax for GLP-1 was also significantly delayed following DRN compared with UN (45 min later;
p
 = 0.26), Cmax did not differ significantly. GLP-1 rose significantly during the last 90 min of the 3-h MTT (β
1
 = 0.16 pg/mL/min,
p
 = 0.025), while following UN it decreased (β
1
 = −0.21 pg/mL/min,
p
 = 0.0026) (
p
difference = 0.0003). There were minimal differences in seven measures of appetite and adverse symptoms between DRN and UN.
Conclusions
We conclude that nutrient can be formulated using all-natural ingredients to induce a delayed rise in GLP-1. Further testing is needed to determine the amount and site of nutrient release, when maximum GLP-1 levels occur, and if modification of the formulation specifications and dose are associated with appetite and glucose control.