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August 2022 - Volume 80 - Issue 2

  • George W. Booz, PhD, FAHA
  • 0160-2446
  • 1533-4023
  • 12 issues per year
  • Cardiac & Cardiovascular Systems 75/143, Pharmacology & Pharmacy 162/279
  • 3.271

A Novel Dual Incretin Agent, Tirzepatide (LY3298176), for the treatment of Type 2 Diabetes Mellitus and Cardiometabolic Health (John Bucheit, Jessica Ayers, Lauren Pamulapati, Audrieanna Browning, Evan Sisson). The incretin hormone system is the target of multiple type 2 diabetes mellitus (T2DM) treatments because defects in this system play major roles in the pathogenesis of diabetes. Currently, the glucagon-like peptide (GLP-1) receptor agonists are recommended for patients with atherosclerotic cardiovascular disease (ASCVD) and those at high risk for ASCVD. In addition to the favorable cardiovascular effects, GLP-1 RAs also provide robust lowering of hemoglobin A1c and weight. While these factors make GLP-1 RAs attractive options for T2DM, the currently available agents have no effect on glucose-dependent insulinotropic polypeptide (GIP). Patients with T2DM are known to have GIP defect which is significant due to its profound insulinotropic effects. Tirzepatide is a novel incretin agent currently under review by the Food and Drug Administration for the treatment of type 2 diabetes. This first-in-class agent serves as a co-agonist for both the GLP-1 and GIP receptors. In this review, we report on the pharmacologic mechanism of GLP-1, GIP and co-agonist effects on the cardiometabolic system. Additionally, we review the glycemic lowering, weight-loss effects, and other cardiometabolic outcomes of tirzepatide based on phase 2 and 3 data. The safety profile of tirzepatide is consistent across all phase 3 trials. The most common adverse effects are gastrointestinal symptoms, but they generally have a low risk for discontinuation. Overall, preliminary data suggests tirzepatide is an efficacious and safe agent for the treatment of T2DM.

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Current Issue Highlights

Review Article

The editors of JCVP are calling for the submission of review articles dealing with all aspects of ER signaling in the heart, including the cGAS–cGAMP–STING pathway, mitochondria associated membranes, unfolded protein response (UPR), inflammasome activation, and ER stress. Articles with a therapeutic and disease-based perspective are welcomed. All articles will undergo peer review and appear in a regular issue in early 2023. Please contact the editorial office for additional information and prior approval for submission. ​​

The Journal of Cardiovascular Pharmacology announces an open call for a new review series dealing with the rapidly developing topic of RNA-based therapies. Reviews should focus on treating cardiovascular diseases or disorders, such as myocardial infarction, cardiac hypertrophy, cardiomyopathies, arrhythmias, valvular heart disease, aortic aneurysms, atherosclerosis and dysliidemia, and cerebrovascular disease. Various approaches, such as RNA aptamers, long non-coding RNAs, microRNAs, antisense nucleotides, and novel delivery strategies are included. The series is scheduled to appear early 2023. Please contact the editorial office for additional information and prior approval for submission.​​

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