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Dual and triple receptor activity (GLP-1, GIP, glucagon) enhances glucose regulation and metabolic outcomes

Activation of these receptors produces several effects: Appetite suppression: GLP-1 agonists activate anorexigenic (appetite-suppressing) POMC/CART neurons and inhibit orexigenic (appetite-stimulating) NPY/AgRP neurons in the hypothalamus, reducing hunger signaling Enhanced satiety: Activation of brainstem GLP-1 receptors amplifies satiety signals from the gastrointestinal tract, causing patients to feel full earlier and longer after meals Reduced food reward: GLP-1 receptor activation in the mesolimbic dopamine system reduces the hedonic drive to eat, diminishing cravings for high-calorie foods (Blundell et al., Diabetes, Obesity and Metabolism , 2017) Peripheral Effects Beyond central nervous system activity, GLP-1 agonists produce peripheral effects that contribute to weight loss: Delayed gastric emptying: GLP-1 receptor activation in the stomach slows gastric motility, prolonging gastric distension and promoting earlier satiety

GLP-1s offer significant promise to millions of Americans living with obesity, diabetes and/or cardiovascular disease, but their unprecedented demand and high price tags are creating challenging downstream impacts, including fluctuating supply, inconsistent clinical support, and runaway cost trajectory, said an Evernorth statement

In February 2025, researchers published findings in JAMA Psychiatry from the first randomized, placebo-controlled clinical trial specifically designed to study this phenomenon

Most patients find that gastrointestinal side effects improve significantly after the first 24 weeks of treatment, and the benefits of the medication become more apparent as tolerance develops