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A century after the discovery of insulin, people with type 1 diabetes continue to experience elevated cardiovascular risk and associated mortality, incompletely explained by dysglycemia and traditional risk factors. There is increasing recognition of the contributions of glycemic variability, insulin-related weight gain, insulin resistance and other hormonal disturbances to this risk, necessitating additional agents targeting these pathways. This article explores these mechanisms and provides an overview of current available agents. Finally, we highlight the sparsity of data on long-term outcomes and hard cardiovascular endpoints.