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Mechanism of Action & Pharmacology Tirzepatide is a synthetic acylated peptide that binds independently and with high affinity to both the glucose-dependent insulinotropic polypeptide (GIP) receptor and the glucagon-like peptide-1 (GLP-1) receptor.[4] This dual incretin mimetic pharmacology activates each receptor pathway through distinct binding interactions, distinguishing it mechanistically from single-receptor GLP-1 agonists.[4] At the GIP receptor, tirzepatide enhances glucose-dependent insulin secretion and supports adipose tissue lipid modulation.[4] Clinical observations suggest GIP activation may also help mitigate some of the gastrointestinal side effects typical of GLP-1 receptor agonism, though its precise contribution to tirzepatides overall clinical profile remains under active evaluation.[3][4] GLP-1 receptor agonism manages glycemic control by stimulating glucose-dependent insulin secretion, suppressing inappropriate glucagon release during hyperglycemia, and delaying gastric emptying to lower postprandial blood sugar spikes.[3][4] Because both receptor pathways operate in a glucose-dependent manner, tirzepatide monotherapy carries a lower intrinsic risk of hypoglycemia than insulin secretagogues.[3][4] However, this risk increases significantly when MOUNJARO is combined with insulin or sulfonylureas.[3][4] Data from the SURPASS phase 3 program demonstrated significant improvements in HbA1c and body weight across the dose range.[4] In the SURPASS-CVOT trial, tirzepatide met its primary endpoint of non-inferiority to dulaglutide for major adverse cardiovascular events (MACE-3), with exploratory analyses suggesting potential cardioprotective benefits.[1] Post hoc cardiorenal analyses of SURPASS-CVOT further showed a lower incidence of a broad composite cardiovascular and kidney endpoint compared to dulaglutide, providing relevant data for managing patients with concurrent cardiorenal risk profiles.[2] Prescribers should review the complete prescribing information before starting therapy.[3][4] Indications & Patient Selection Regional labeling determines which indications apply in a given market

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Physiology - Endocrinol