Advancing Type 1 Diabetes Management: Integrating Novel Therapies, Technologies, and Adjunctive Approaches

In type 1 diabetes, a condition that necessitates lifelong exogenous insulin replacement, there is heavy reliance on technology-assisted insulin delivery and glucose monitoring. Yet, people living with type 1 diabetes still face dysglycemia, weight gain, vascular complications, ketoacidosis and severe hypoglycemia, and psychological distress. Cardiovascular and kidney disease remain the leading causes of morbidity and mortality, yet traditional risk factors (smoking, hypertension, hyperlipidemia, obesity, hyperglycemia) incompletely explain this excess burden. Emerging evidence highlights the role of insulin resistance, inflammation, and endothelial dysfunction exacerbated by current subcutaneous insulin therapies in type 1 diabetes, independent of overweight/obesity status. This has fueled interest in addressing metabolic challenges in type 1 diabetes through novel insulin analogs, adjunctive noninsulin therapies, and integrated technologies. Our review explores the potential synergy between technologies and adjunctive therapeutics to address unique physiologic drivers of metabolic dysfunction in type 1 diabetes. Innovations such as multihormonal systems, dynamic glucose and ketone monitoring, and automated insulin titration hold promise. However, leveraging emerging insights from nutrient-stimulated hormone-based therapies and other drug classes such as insulin-sensitizing agents and sodium-glucose cotransporter 2 inhibitors could pave the way for designing combination type 1 diabetes-specific therapies. Large, placebo-controlled trials are needed to progress the field toward use of combination therapies that reduce metabolic and vascular complications and ease patient burden in type 1 diabetes.