Tirzepatide: Clinical review of the “twincretin” injectable

Abstract

Disclaimer In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose To provide an overview of the safety and efficacy, pharmacology, dosing, place in therapy, and clinical trials for tirzepatide, a novel glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) agonist for treatment of type 2 diabetes. Summary Diabetes is a chronic disease state with a high burden on healthcare spending and patient quality of life. Incretin-influencing agents such as GLP-1 receptor agonists have gained favor as diabetes therapeutic options due to their impact on multiple glycemic factors as well as resulting weight loss and cardiovascular benefits. Tirzepatide was approved in 2022 for the management of type 2 diabetes and utilizes GLP-1 receptor agonism along with GIP agonism to simultaneously address 2 incretin pathways. Thus far, the SURPASS and SURMOUNT trials, for which findings have been published, have shown great efficacy of tirzepatide in glycosylated hemoglobin and weight reduction in multiple subgroup populations with and without diabetes. Tirzepatide has similar gastrointestinal adverse reactions and contraindications as traditional GLP-1 receptor agonists. Conclusion Tirzepatide is a novel agent on the market for type 2 diabetes management that offers targeting of a familiar pathway along with the new GIP pathway to address glycemic control in patients with diabetes. Tirzepatide is approved for use in patients with diabetes and may serve as a strong option for patients requiring improved glycemic and weight control.

Glucagon‐like peptide agonists: A prospective review

“…This novel mechanism of action underlines the uniqueness of tirzepatide as a treatment option for type II diabetes, making it a promising avenue for improved glycemic control in affected individuals. 83,84 Besides tirzepatide, the efficacy, safety, and pharmacokinetic/ pharmacodynamic characteristics of efpeglenatide, a long-acting GLP1RA, were tested clinically. 85 Two studies concluded that efpeglenatide serum concentrations increased proportionally with the administered dose.…”

“…Additionally, the drug displays imbalanced agonism at the GIPR and GLP‐1R, leading to biased signalling at the GLP‐1R. This novel mechanism of action underlines the uniqueness of tirzepatide as a treatment option for type II diabetes, making it a promising avenue for improved glycemic control in affected individuals 83,84 …”

“…This novel mechanism of action underlines the uniqueness of tirzepatide as a treatment option for type II diabetes, making it a promising avenue for improved glycemic control in affected individuals. 83 , 84 …”