GIP (glucose-dependent insulinotropic polypeptide) was historically considered primarily a glucose-dependent insulin secretagogue, but tirzepatide's development revealed additional metabolic roles: Central appetite regulation : GIP receptors in the hypothalamus and brainstem contribute to satiety signaling through pathways distinct from GLP-1 Adipose tissue effects : GIP receptors on adipocytes modulate lipid storage and adipokine secretion Beta-cell protection : GIP signaling supports pancreatic beta-cell survival and proliferation Bone metabolism : GIP has anti-resorptive effects on bone, potentially mitigating osteoporosis risk during weight loss GLP-1 receptor agonism provides complementary glucose-lowering and appetite-suppressing effects, as described above
Side effects, including nausea, vomiting, and fatigue, are a frequent result
According to Rajiv Kovil, a medical expert in diabetes and weight-loss drugs, retatrutide could be the "biggest molecule" because of its action on the three receptors
Several landmark cardiovascular outcome trials have demonstrated that GLP-1RAs can significantly reduce the risk of major adverse cardiovascular events (MACE), which include cardiovascular death, nonfatal myocardial infarction (heart attack), and nonfatal stroke [43]