Infographic: Where GLP-1s Work Now -- and What's Coming
Glucagon-like peptide-1 (GLP-1) receptor agonists are arguably the medication class of the moment. First used to treat type 2 diabetes, then people with overweight or obesity, these agents have been making headlines for the past few years. Yes, they can be costly and there are reports of side effects, but those two factors have not appeared to dampen the enthusiasm around the GLP-1 receptor agonists.
Beyond their effectiveness, researchers are looking at their mechanisms of action. How, exactly, do medications with household names like Ozempic, Wegovy, or Mounjaro actually work?
Also, investigators are thinking beyond diabetes and weight management to expanded medical indications for the GLP-1 receptor agonists. Although in the early phases of research, these agents could show promise for improving cardiovascular outcomes or neurologic conditions like Parkinson's disease or Alzheimer's disease, for example.
Medscape created this infographic to show the organ systems and areas of the body where GLP-1 receptor agonists are or could soon be shown to have beneficial effects. The Notes section highlights evidence for the mechanism of action for these different indications.
Brain effects.
GLP-1 receptor agonists can cross the blood-brain barrier and work on the brain's satiety center and decrease desire for food. Recent evidence suggests that these medications can also reduce inflammation in the brain, prompting research on whether they will have a role in treating Parkinson's disease or Alzheimer's disease in the future.
Improved cardiovascular outcomes.
It's not completely clear how GLP-1 receptor agonists can improve cardiovascular health, although leading theories include increased vasorelaxation, protection against injury from ischemia and reperfusion and/or improvements in myocardial contractility. Other physiologic effects of these agents, including weight loss, blood pressure control, and lower risk for severe hypoglycemia probably also contribute to beneficial cardiovascular effects.
Slower peristalsis and gastric emptying.
GLP-1 receptor agonists slow gastric emptying, which is associated with weight loss. While this factor can cause adverse effects in some patients, many people return to normal within weeks of starting the medications. The agents also slow gastric motility by decreasing peristalsis and slowing activity of the pylorus, the opening between the stomach and duodenum, which delays gastric emptying.
Blood glucose control.
The GLP-1 receptor agonists release the body's own insulin, "with a low incidence of hypoglycemia, which is an Achilles heel of traditional insulin use." They also decrease the release of glucagon by pancreatic cells and help maintain glucose homeostasis after eating.
Liver, kidney, and systemic effects.
GLP-1 receptor agonists bind to receptors located throughout the body. For example, in addition to the pancreas, brain, heart, and stomach GLP-1 receptors are found on cells in the lung, gastrointestinal tract, kidney, and liver. Experts are reporting beneficial effects on the kidney and liver associated with the GLP-1 receptor agonists.
Facilitate weight loss.
GLP-1 receptor agonists facilitate weight loss by slowing stomach emptying and stimulating brain areas that control appetite, including promoting a feeling of satiety.
Possible future indications.
Researchers are investigating new, potential roles for treatment with GLP-1 receptor agonists, including treating alcohol use disorder or for reducing risk of colorectal cancer.
