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This is in line with the fact that, although some studies have shown the presence of the GLP-1R in other parts of the heart ( Apart from the chronotropic effects, direct effects of GLP-1 specifically on the heart have not been comprehensively documented, although evidence exists to suggest that GLP-1 RAs may improve cardiac output as well as cardiomyocyte survival ( It should be noted that one of the two major DPP-IV-generated truncated forms of GLP-1 (GLP-1 [9-36amide]) has been shown to have direct beneficial cardiac effects in mice, which is representative of the hypothesis that a GLP-1R-associated response can be elicited also by these metabolites and thus not only via the classic incretin pathway ( Future perspectives In summary, the cardiovascular safety of all currently marketed GLP-1 RAs has been thoroughly established in large CVOTs ( As noted by others ( Of note, the finding of a markedly greater benefit on HF of efpeglenatide amongst trial participants using SGLT2 inhibitors at enrolment in the AMPLITUDE-O CVOT highlights another important point ( Another drug class widely used to treat type 2 diabetes is inhibitors of the enzyme dipeptidyl peptidase-4 (DPP4), which mediates enzymatic breakdown of GLP-1

TODAY Study Group, Bjornstad P, Drews KL et al (2021) Long-term complications in youth-onset type 2 diabetes

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