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The adiponectin gene is located on chromosome 3q26, a region highly susceptible to the development of metabolic syndrome and Type 2 diabetes mellitus. Research conducted on the Pima Indians of Arizona, a population with the highest known prevalence of Type 2 diabetes, has shown low adiponectin levels are associated with insulin resistance, whereas higher concentration of adiponectin helped protect against development of Type 2 diabetes. CNIs in addition to increasing insulin resistance, induces pancreatic beta cell apoptosis if administered in large doses., resulting in decreased insulin secretion. Thus CNIs, while effective in preventing organ rejection, disrupt glucose metabolism by increasing insulin resistance and reducing insulin secretion leading to abnormalities in the glucose homeostasis (Figure 1)

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In three nested casecontrol studies from England and Wales, involving 440,089 patients with T2DM and without ASCVD treated with non-insulin glucose-lowering medication, combined SGLT2i and GLP-1RA therapy used for primary prevention was associated with 30% lower odds of MACE (defined as myocardial infarction/acute coronary syndrome, stroke/transient ischemic attack, and/or cardiovascular death) compared with other combination regimens (OR, 0.70

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