Among the gastrointestinal hormones, the incretins: glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 have attracted interest because of their importance for the development and therapy of type 2 diabetes and obesity.
Glucagon-like peptide-1 (GLP-1) and strategies based on this blood sugar-reducing and appetite-suppressing hormone are used to treat obesity and type-2 diabetes.
Thus, the postprandial GLP-1 response is not necessarily decreased but rather enhanced during obesity development, which is likely to play a protective role against glucose intolerance.
In this review, we first summarize our traditional understanding of the physiology of GIP and GLP-1, and our current knowledge of the relationships between GIP and GLP-1 and obesity and diabetes.
A synthetic monomeric peptide triple receptor agonist, termed "Triagonist" that incorporates glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon (Gcg) actions, was previously developed to improve upon metabolic and glucose regulatory benefits of single and dual receptor agonists in rodent models of diet-induced obesity and type 2 diabetes.
One such hormone, glucagon-like peptide-1 (GLP-1), has received significant attention in the treatment of obesity and diabetes due to its potent incretin effect.
These results suggest that enhancement of the postprandial GLP-1 response during obesity development has a role in maintaining a normal postprandial glycaemic response.
Liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, and phentermine, a psychostimulant structurally related to amphetamine, are drugs approved for the treatment of obesity and hyperphagia.
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.
These preclinical results suggested that PP18, as a novel OXM-based dual GLP-1 and glucagon receptor agonist, may serve as a novel therapeutic approach to treat T2DM and obesity.
Enteroendocrine L-cell derived peptide hormones, notably glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2), have become important targets in the treatment of type 2 diabetes, obesity and intestinal diseases.
In addition, we discuss recent developments of therapeutic approaches in the treatment of obesity and diabetes by dual- and tri-agonist molecules based on combinations of glucagon with other peptides.
GLP-1 regulates testicular energy homeostasis and pharmacological use of GLP-1 analogues could be valuable to counteract the negative impact of obesity in male reproductive function.
The numerous beneficial effects of GLP-1 render this hormone an interesting candidate for the development of pharmacotherapies to treat obesity, diabetes, and neurodegenerative disorders.
A dual incretin receptor agonist designed to co-activate GLP-1 and GIP receptors was recently shown to elicit robust improvements of glycemic control (mean haemoglobin A1c reduction of 1.94%) and massive body weight loss (mean weight loss of 11.3 kg) after 26 weeks of treatment with the highest dose (15 mg once weekly) in a clinical trial including overweight/obese patients with type 2 diabetes.
Larger interventional studies are needed to establish the role of preconception intervention with GLP-1 based therapies, assessing fertility outcomes in obesity, PCOS, and diabetes-related fertility problems.
However, independent of lipid loads, GMET and OCTT were slower (GMET<sub>lipid</sub> P = 0.046; GMET<sub>water</sub> P = 0.003; OCTT P = 0.001), and basal and postload secretion of glucagon-like peptide-1 (GLP-1) was attenuated ( P = 0.045 and P = 0.048, respectively) in men with severe obesity compared with men without obesity.