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A meta-regression study suggested a linear relationship between HbA1c reduction and MACE risk in patient with arGLP-1.89 Publication on mediation analyses also suggest that cardiovascular benefit could be mediated in part by effects on HbA1c, on blood pressure or reduction in urine albumin-creatinine ratio90,91 (see below), as well as by their effect on lipid profile.81 However, in subgroup analyses of cardiovascular safety studies, baseline HbA1c, weight, previous cardiovascular disease, or renal function did not predict the beneficial effects of these drugs on MACE,87 so other mechanisms, such as the previously mentioned anti-inflammatory, antifibrotic, antiatherogenic, vasodilator, or endothelial function-enhancing effects, have been suggested to influence the cardiovascular benefit of these drugs29,78 (Fig