Next generation obesity drug
Retatrutide is being developed by pharmaceutical giant Eli Lilly, which also makes tirzepatide, a powerful dual-action treatment for obesity (Zepbound) and type 2 diabetes (Mounjaro). Both drugs rely on semaglutide (Ozempic/Wegovy), a GLP-1-based obesity drug, from pharmaceutical company Novo Nordisk. Tirzepatide targets not only GLP-1 (aka Glucagon-like peptide-1), but also GIP (aka glucose-dependent insulinotropic polypeptide).
Retatrutide builds on these drugs by adding glucagon to the combination of GLP-1 and GIP. These three hormones have overlapping roles in the response to food, helping the body regulate blood sugar, feelings of fullness, how much we eat, and downstream metabolic factors.
The interaction between the three hormones is complex and they have different activities in different places in the body and at different times. GIP is secreted by cells (K cells) located in the first sections of the small intestine, just after the stomach. This hormone is best known for stimulating the release of insulin in response to glucose (sugar). But GIP has other activities, including triggering the breakdown of triglycerides (a type of fat in the blood) and working the brain to trigger the feeling of fullness. It also plays a role when blood sugar gets too low. In this case, GIP stimulates an increase in glucagon.
Glucagon is a hormone released by alpha cells in the pancreas and acts against some of the main roles of GIP and GLP-1. Glucagon is best known for triggering the release of glucose and fatty acids into the blood, which it does when blood sugar levels become too low (hypoglycemia). But after meals, glucagon also appears to play a role by increasing insulin production, delaying stomach emptying, and regulating lipid levels.
GLP-1, the best-known hormone, is produced by cells (L cells) located further in the gastrointestinal tract, particularly at the end of the small intestine (the ileum) and the colon. GLP-1 acts in response to sugar to increase insulin release. It delays emptying of the stomach and acts on the brain to trigger the feeling of fullness. It can also send signals to stimulate the breakdown of lipids in fatty tissues. Additionally, GLP-1 and GIP can stimulate the release of another hormone, called adiponectin, which can help combat insulin sensitivity and reduce inflammation.
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