Type 1 Diabetes management needs agents beyond insulin to address cardiovascular risk and metabolic disturbances

Despite a century of insulin therapy, individuals with Type 1 Diabetes Mellitus (T1D) continue to face significantly elevated cardiovascular risk and associated mortality. This persistent risk is not fully explained by dysglycemia or traditional risk factors, highlighting a critical gap in current T1D management. The standard-of-care, while life-saving, often overlooks the complex interplay of glycemic variability, insulin-related weight gain, insulin resistance, and other hormonal disturbances that contribute to long-term complications. Addressing these multifaceted challenges necessitates a paradigm shift towards adjunctive therapies that complement insulin's glucose-lowering effects.

This review article systematically explored the mechanisms underlying the persistent cardiovascular risk in Type 1 Diabetes patients despite insulin therapy. The authors synthesized existing literature to identify key physiological pathways and hormonal imbalances contributing to this risk. Furthermore, the review provided a comprehensive overview of currently available adjunctive agents that target these specific pathways, evaluating their potential to mitigate the identified complications. The scope included an examination of how these agents address issues such as glycemic variability, insulin resistance, and insulin-related weight gain, aiming to highlight the necessity for a broader therapeutic approach beyond insulin monotherapy.

The review identified that glycemic variability, insulin-related weight gain, insulin resistance, and other hormonal disturbances are significant, often underappreciated, contributors to the elevated cardiovascular risk in individuals with Type 1 Diabetes. These factors collectively explain the incomplete protection offered by insulin monotherapy against long-term complications. The authors highlighted that while several adjunctive agents are available, targeting pathways like GLP-1R or SGLT2, their long-term efficacy and impact on hard cardiovascular endpoints in T1D populations remain largely understudied. The review underscored a critical knowledge gap: > The sparsity of data on long-term outcomes and hard cardiovascular endpoints for these additional agents in Type 1 Diabetes patients is a major limitation, preventing a full understanding of their potential benefits in reducing mortality and morbidity. This emphasizes the urgent need for more robust, long-term clinical trials to validate the role of these therapies.