Intestinal-related substances in obesity regulation: A comprehensive review

Table 3 The role of peptides in the gut

Affiliation	Method	Result	Conclusion	Ref.
Eli Lilly and Company, United States	Administer once weekly. Phase 1 included SAD, MAD, and POC with dulaglutide as control.	LY3298176 activated GIP/GLP-1 receptors, improving glucose tolerance and reducing weight/food intake in mice	This drug achieves the goal of weight loss by reducing food intake and lowering blood sugar	[31]
National University Health System, Singapore	Evaluate GLP-1 RAs on weight, BMI, and waist circumference in overweight/obese adults. 47 RCTs included	GLP-1 RAs reduced weight, BMI, and waist	GLP-1 RAs demonstrated significant weight, BMI, and waist circumference reduction benefits	[29]
McGill University Health Centre, Canada	Narrative review using keywords on GLP-1-based therapies, obesity, and energy regulation	GLP-1 RAs act centrally and peripherally to reduce appetite, improve glucose control, and enhance metabolic health	GLP-1 RAs regulate obesity via central/peripheral mechanisms, suppressing appetite and improving metabolism	[28]
King Saud University, Saudi Arabia	Review of gut hormones' role in obesity, SCFAs, and protein-based interventions. Covered GLP-1, PYY, ghrelin, individual/combined therapies, and SCFAs' influence on hormone secretion	GLP-1 RAs and PYY reduce intake/weight, while SCFAs stimulate GLP-1/PYY for satiety/weight control	PYY and GLP-1 receptor mechanisms drive weight loss by regulating appetite and energy balance through gut hormone modulation	[4]
University of Texas Southwestern Medical Center, United States	Explored ghrelin’s effect on insulin, glucagon, and CNS, and glucose’s feedback on ghrelin secretion	Ghrelin increases blood glucose, reduces insulin effects, and worsens glucose tolerance. May contribute to hyperglycemia in obesity/diabetes	Ghrelin elevates blood glucose via insulin resistance and appetite stimulation, promoting obesity; blocking its action aids weight loss	[45]

GLP-1 RA: Glucagon-like peptide-1 receptor agonist; GIP: Glucose-dependent insulinotropic polypeptide; PYY: Peptide YY; CCK: Cholecystokinin; HFD: High-fat diet; RCT: Randomized controlled trial; SAD: Single ascending dose; MAD: Multiple ascending dose; POC: Proof-of-concept.