Targeting GLP-1 For Obesity & Blood Sugar Management

Targeting GLP-1 For Obesity & Blood Sugar Management

GLP-1 is a therapeutic target with good promise due to its beneficial effects on several metabolic abnormalities linked to T2D and essential factors in weight loss and maintenance. GLP-1 has been investigated concerning the pathogenesis and therapy of T2D and obesity. Although a few studies have produced inconclusive results, it is generally agreed that obesity and the metabolic alterations caused by the onset of T2D are linked to a decrease in the postprandial release of GLP-1 from L-cells. This alteration in GLP-1 secretion over time may speed up weight gain and slow the course of T2D.

Numerous researchers have looked at the metabolic effects of intravenous delivery of GLP-1 agonists as a potential method to improve GLP-1 actions. Intriguingly, people with obesity and T2D showed metabolic and appetite responses that were very similar to those of their healthy counterparts when given the same dose of a GLP-1 analog. This finding suggests that sensitivity to GLP-1's activity is maintained, contrary to several other peptide hormones involved in maintaining blood glucose and energy levels.

As a result, targeting GLP-1 receptor activation with GLP-1 analogs and lengthening GLP-1 half-life in the bloodstream became important to treat obesity and T2D.

Due to this, two types of pharmaceutical agents—GLP-1 receptor agonists and DDP-IV inhibitors—were created. GLP-1 receptor agonists have just received approval in the United States for treatment of obesity. They are commonly used to control blood glucose levels in people with T2D. Like DDP-IV inhibitors, endogenous GLP-1 catabolic deactivation is prevented by using them alone or in conjunction with other drugs.

Pharmaceutical agents that target GLP-1's action are associated with lower risks of hypoglycemia than other commonly prescribed antihyperglycemic medications like sulfonylureas and thiazolidinedione. They also have the advantage of promoting weight loss and may prevent or at least delay the progressive decline in pancreatic-cell function, which typically necessitates increasing drug dosage. GI discomfort, nausea, and vomiting are the side effects associated with the usage of these drugs that are most frequently reported.

Increasing GLP-1's endogenous secretion from L-cells is a pertinent, though less researched, method of enhancing its activity. Pharmacological and nutritional methods may be used to accomplish this. The main criticism of dietary methods is that they might not raise GLP-1 blood concentrations enough to support advantageous physiological activities like better insulin production and blood glucose levels. Depending on the drug, GLP-1 receptor agonists imitate supraphysiological blood concentrations of GLP-1 and have a much longer half-life, ranging from 1.5 hours to 5 days. However, endogenous GLP-1 uses both endocrine and neural pathways to exercise its effects, whereas GLP-1 receptor agonists only do so by endocrine route, suggesting that such high concentrations may not be necessary. According to variations in GLP-1 blood concentrations, a rise within physiologically normal blood concentrations may be sufficient to generate positive metabolic benefits after bariatric surgery.

Numerous studies have demonstrated that 6–12 months following a Roux-en-Y gastric bypass, GLP-1 blood concentrations might increase up to fourfold.

This rise in GLP-1 levels is linked to better nutritional intake and choices, more weight loss, better glycemic management, and frequent T2D resolution. When compared to persons with morbid obesity (13.5 6.9 pmol/L), people who underwent Roux-en-Y gastric bypass within 36 months had considerably greater GLP-1 blood concentrations 30 minutes after eating (47.4 11.4 pmol/L) than those who did not. Since postprandial GLP-1 concentrations in patients with Roux-en-Y gastric bypass were within physiologically normal ranges, it is conceivable that dietary strategies that increase postprandial GLP-1 secretion will have similar long-term effects on food intake, glycemic control, and weight management.

Back to blog