The pharmaceutical landscape for metabolic health has been transformed by a class of medications known as Glucagon-like peptide-1 (GLP-1) receptor agonists. These treatments mimic a naturally occurring hormone that plays a significant role in regulating appetite and blood sugar, making them highly effective for managing type 2 diabetes and promoting weight loss. Eli Lilly and Company stands as a major contributor to this field, developing both single-action and next-generation dual-action therapies that have been widely adopted. This article will explore the biological actions of this drug class, detail the specific medications developed by Eli Lilly, and explain the practical considerations for their use.
Understanding the GLP-1 Mechanism of Action
These medications imitate Glucagon-like peptide-1 (GLP-1), an incretin hormone released by the gut in response to eating. The natural hormone has a short half-life and is quickly broken down by the body’s enzymes. Synthetic drug versions are engineered to resist this rapid degradation, allowing them to remain active for days or weeks. These molecules bind to and activate GLP-1 receptors throughout the body, triggering a cascade of beneficial metabolic effects.
A primary function is the glucose-dependent stimulation of insulin release from pancreatic beta cells. The drug prompts the pancreas to secrete insulin only when blood glucose levels are elevated, which lowers the risk of hypoglycemia compared to older diabetes medications. GLP-1 agonism also suppresses the release of glucagon, a hormone that instructs the liver to produce and release stored sugar. Reducing this sugar output helps stabilize blood glucose concentrations.
The third major mechanism involves the gastrointestinal tract. Activation of GLP-1 receptors significantly slows the rate at which the stomach empties its contents into the small intestine, a process known as delayed gastric emptying. This slower digestion helps prevent sharp blood sugar spikes after a meal and contributes to a prolonged feeling of fullness.
The hormone also acts on receptors in the hypothalamus and brainstem, regions of the brain responsible for regulating appetite. This action reduces hunger signals and decreases overall caloric intake, driving the substantial weight reduction observed with these therapies. These combined actions represent the core physiological impact of the drug class.
Eli Lilly’s Portfolio of GLP-1 and Dual Agonist Medications
Eli Lilly’s portfolio includes a single-action GLP-1 receptor agonist and a newer dual-action therapy. The initial entry was dulaglutide (Trulicity), which activates only the GLP-1 receptor. Dulaglutide is administered once weekly and is approved for improving blood sugar control in adults with type 2 diabetes.
The more recent advancement is tirzepatide, a dual agonist. It activates both the GLP-1 receptor and the receptor for Glucose-dependent Insulinotropic Polypeptide (GIP). This dual targeting leverages the synergistic effects of both hormones, leading to a more profound metabolic response than targeting GLP-1 alone.
Tirzepatide is available under two brand names depending on the indication. Mounjaro is prescribed for the treatment of type 2 diabetes. Its dual mechanism has demonstrated superior efficacy in lowering hemoglobin A1c levels and promoting weight loss compared to earlier single-action GLP-1 therapies.
The same molecule is marketed as Zepbound for chronic weight management in adults with obesity or overweight with at least one weight-related condition. Zepbound’s approval reflects its powerful effect on appetite regulation and body weight reduction. This dual GIP/GLP-1 approach enhances the insulin-releasing effect and improves lipid metabolism compared to single agonists.
The structural difference between single and dual agonism explains the clinical distinction. While dulaglutide is effective for glucose control, tirzepatide’s dual-action provides a more comprehensive metabolic signal. This enhanced signaling results in greater reductions in body weight and improved glycemic control.
Practical Considerations: Dosing and Common Side Effects
Both dulaglutide and tirzepatide are administered via subcutaneous injection into the fatty tissue just under the skin. The drugs are formulated for once-weekly dosing, enhancing patient convenience compared to therapies requiring daily injections. The injection is performed using a pre-filled pen device, simplifying the process for at-home use.
A gradual dose escalation schedule is standard practice when initiating treatment. For tirzepatide, patients begin with a low starting dose, such as 2.5 milligrams, for four weeks. The dose is then increased in 2.5 milligram increments every four weeks, as tolerated, until a therapeutic maintenance dose (5 mg to 15 mg) is reached.
This slow titration process is designed to mitigate the severity of common adverse events, which are predominantly gastrointestinal. Patients frequently report side effects such as nausea, vomiting, diarrhea, and constipation. These digestive symptoms are a direct consequence of the drug’s mechanism, specifically slowed gastric emptying.
The frequency and intensity of these gastrointestinal issues are often highest immediately following a dose increase but tend to decrease as the body adjusts over time. Other side effects include abdominal pain and decreased appetite, which is an expected therapeutic effect contributing to weight loss. Patients should stay well-hydrated and manage their diet, especially during the initial phase of treatment, to minimize temporary digestive discomforts.