From the Guidelines
GLP-1 (glucagon-like peptide-1) is a hormone that regulates blood sugar levels and appetite by stimulating insulin release, suppressing glucagon secretion, slowing gastric emptying, and acting on the brain's appetite centers to reduce hunger. This combination of effects has made synthetic GLP-1 receptor agonists valuable medications for treating type 2 diabetes and obesity, as they mimic natural GLP-1 but last much longer in the body 1. The hormone's blood sugar-regulating and appetite-suppressing properties work together to help maintain metabolic balance in the body. GLP-1 receptor agonists have been shown to reduce blood glucose by activating the GLP-1 receptors, enhancing insulin secretion and inhibiting glucagon secretion in a glucose-dependent manner, delaying gastric emptying, and reducing food intake via central appetite suppression 1.
Some of the key effects of GLP-1 include:
- Stimulating insulin release from the pancreas when blood sugar rises
- Suppressing glucagon secretion to help lower blood glucose
- Slowing gastric emptying to make individuals feel fuller longer after eating
- Acting on the brain's appetite centers to reduce hunger
- Promoting weight loss by delaying gastric emptying and increasing satiety 1
GLP-1 receptor agonists are currently delivered by subcutaneous injection and have high glucose-lowering efficacy, with minimal risk for hypoglycemia, but may increase the hypoglycemic potential of insulin and sulfonylureas when combined with those medications 1. The use of GLP-1 receptor agonists has been recommended in patients with type 2 diabetes, particularly those with established cardiovascular disease or at high risk for cardiovascular events, to reduce major adverse cardiovascular events, hospitalization for heart failure, and cardiovascular death 1.
Overall, the use of GLP-1 receptor agonists is a valuable treatment option for patients with type 2 diabetes and obesity, due to their ability to regulate blood sugar levels and appetite, while also providing cardiovascular benefits.
From the FDA Drug Label
Liraglutide is an acylated human Glucagon-Like Peptide-1 (GLP-1) receptor agonist with 97% amino acid sequence homology to endogenous human GLP-1(7-37). GLP-1(7-37) represents <20% of total circulating endogenous GLP-1 Like GLP-1(7-37), liraglutide activates the GLP-1 receptor, a membrane-bound cell-surface receptor coupled to adenylyl cyclase by the stimulatory G-protein, Gs, in pancreatic beta cells. Liraglutide increases intracellular cyclic AMP (cAMP) leading to insulin release in the presence of elevated glucose concentrations This insulin secretion subsides as blood glucose concentrations decrease and approach euglycemia. Liraglutide also decreases glucagon secretion in a glucose-dependent manner. OZEMPIC is a glucagon-like peptide 1 (GLP-1) receptor agonist indicated as: • an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (1). • to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease (1)
GLP-1 increases insulin release in the presence of elevated glucose concentrations and decreases glucagon secretion in a glucose-dependent manner. It also delays gastric emptying, reducing the rate at which postprandial glucose appears in the circulation 2. GLP-1 receptor agonists, such as liraglutide and semaglutide, are used to improve glycemic control in adults with type 2 diabetes mellitus and to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease 3.
- Key effects of GLP-1:
- Increases insulin release
- Decreases glucagon secretion
- Delays gastric emptying
- Clinical uses of GLP-1 receptor agonists:
- Improve glycemic control in type 2 diabetes mellitus
- Reduce the risk of major adverse cardiovascular events in type 2 diabetes mellitus with established cardiovascular disease
From the Research
Functions of GLP-1
- GLP-1 is a secreted peptide that acts as a key determinant of blood glucose homeostasis by virtue of its abilities to slow gastric emptying, to enhance pancreatic insulin secretion, and to suppress pancreatic glucagon secretion 4.
- GLP-1 stimulates insulin secretion through potentiating the insulinotropic action of glucose, and it also inhibits glucagon secretion and gastric emptying 5.
- The peptide has cardio- and neuroprotective effects, decreases inflammation and apoptosis, and has implications for learning and memory, reward behavior, and palatability 6.
Mechanisms of Action
- GLP-1 activates enteric and autonomic reflexes while also circulating as an incretin hormone to control endocrine pancreas function 4.
- The GLP-1 receptor (GLP-1R) is a G protein-coupled receptor that is activated directly or indirectly by blood glucose-lowering agents currently in use for the treatment of type 2 diabetes mellitus (T2DM) 4.
- GLP-1 receptor agonists (GLP-1 RAs) share common mechanisms of action: augmentation of hyperglycemia-induced insulin secretion, suppression of glucagon secretion at hyper- or euglycemia, deceleration of gastric emptying preventing large post-meal glycemic increments, and a reduction in calorie intake and body weight 7.
Therapeutic Implications
- GLP-1 has been suggested as a therapeutic alternative in diabetes due to its integrated action on carbohydrate metabolism, resulting in reduction of circulating glucose 5.
- GLP-1 RAs are successfully in clinical use for the treatment of type-2 diabetes, and several GLP-1-based pharmacotherapies are in clinical evaluation for the treatment of obesity 6.
- GLP-1 RAs can effectively prevent CV events such as acute myocardial infarction or stroke and associated mortality, and may also help prevent renal complications of type 2 diabetes 7.