Evaluating the Impact of Novel Incretin Therapies on Cardiovascular Outcomes in Type 2 Diabetes: An Early Systematic Review

This systematic review is registered with CRD42024507397 protocol number and aims to compare the known data about retatrutide on long-term cardiovascular (CV) protection with tirzepatide, an incretin with recent proven CV benefits. The inclusion criteria were (i) original full-text articles that are randomized control or clinical trials; (ii) published within the last ten years; (iii) published in English; and (iv) conducted on adult human populations. The exclusion criteria were articles deruled on cell cultures or mammals. Studies were selected if they (1) included patients with type 2 diabetes mellitus (DM) and CV risk; (2) patients that received either tirzepatide or retatrutide; and (3) provided sufficient information such as the corresponding 95% confidence intervals or at least a sufficient -value. Studies were excluded if they were a letter to the editor, expert opinions, case reports, meeting abstracts, or reviews; redundant publications; or needed more precise or complete data. The seven included studies were assessed for bias with the Newcastle Ottawa scale, heterogenous, and emphasized the potential CV beneficial effect of type 2 DM (T2DM) therapies (glycemia, glycated A1c hemoglobin, body weight, lipid profile, blood pressure and renal parameter). Further, longer follow-up studies are necessary to verify the long-term CV protection, standardize the specific aspects of CV risk, and compare with subjects without T2DM for a more integrative interpretation of the CV effects independent of the improvement of metabolic activity.