Metformin and Automated Insulin Delivery System Effects on Renal Vascular Resistance and Vascular and Endothelial Function in Youth with Type 1 Diabetes Pilot Study

Diabetic kidney disease (DKD) and cardiovascular disease (CVD) remain the leading causes of morbidity and mortality in people with type 1 diabetes (T1D) and are exacerbated by longer diabetes duration and time outside goal glycemic range. Yet, T1D pathophysiology extends beyond beta cell injury and insulin deficiency and includes insulin resistance (IR), possibly secondary to excess peripheral insulin exposure, and renal vascular resistance (RVR), factors that accelerate CVD risk. We demonstrated metformin improved peripheral insulin sensitivity (IS) and vascular stiffness in youth with T1D on insulin injections or standard insulin pumps. However, metformin's effects on kidney and endothelial outcomes, and the effects of advanced diabetes technologies plus metformin on any cardiovascular or kidney outcome, remains unknown. Automated insulin delivery (AID) systems combine an insulin pump, continuous glucose monitor, and control algorithm to modulate background insulin, decrease peripheral insulin exposure, improve time in target range, and reduce hypoglycemia. We hypothesize that AID systems plus metformin may modulate RVR and vascular/endothelial function, thereby affecting cardiometabolic function, and propose an open label pilot study of 3 months metformin 2,000mg daily in 12 youth (12-21 years) with T1D on AID systems to evaluate for changes in gold-standard measures of RVR, arterial stiffness, and endothelial function.