Modelling Studies to Assess Sodium-Glucose co-Transporter-2 (SGLT2) Inhibition Effects and Kidney Protection in Type 1 Diabetes

Diabetes is a growing public health issue that is estimated to affect over 463 million adults worldwide. Patients with diabetes are characterized by chronically elevated blood sugar (glucose) and are categorized into three main subtypes - type 1 diabetes (T1D), type 2 diabetes (T2D), and gestational diabetes. T1D occurs when the pancreas is unable to produce insulin whereas T2D occurs when the body does not respond to insulin, gestational diabetes is high blood glucose that develops during pregnancy and usually disappears after giving birth. Type 1 diabetes (T1D) is associated with an increased risk in mortality compared to the general population, with premature cardiovascular disease (CVD) and chronic kidney disease (CKD) being leading causes of reduced life expectancy. Although less common compared to type 2 diabetes (T2D), T1D afflicts approximately 9 million people worldwide. Given that the coexistence of CVD and kidney disease is more prevalent within the T1D population, it is imperative to proactively develop tools to prevent diabetes-associated complications.

This project aims to provide new insights into how sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiorenal risk as well as societal costs due to type 1 diabetes (T1D). SGLT2 inhibitors are a class of prescription medicines that are for use with diet and exercise to lower blood sugar in adults with type 2 diabetes. They work by causing the kidneys to remove sugar from the body through urine.

We will use data analysis tools to evaluate potential its effects on markers of long-term diabetic kidney disease (DKD) outcomes and physiological factors associated with kidney health and disease in T1D. The overarching aim of this project is to determine if the mechanisms associated with kidney-heart protection in T2D are also present in people with T1D. We will use previous insights from people with T2D and non-diabetic chronic kidney disease (CKD) to assess long-term clinical benefits on kidney and cardiovascular risk with SGLT2 inhibition in T1D.

Regardless of the magnitude of anticipated benefits, these analyses will be informative for our ultimate goal of designing a larger clinically meaningful trial in collaboration with the Preventing Early Renal Function Loss (PERL) consortium to assess kidney function loss. The PERL consortium is a group of high-quality academic centres and investigators focused on preventing kidney dysfunction. Results of the study will support ongoing efforts to design a clinical trial examining the use of SGLT2 inhibitors in patients with T1D. This may potentially extend the use of these agents with associated heart and kidney protective benefits to a patient population with limited therapeutic options. The ultimate goal of this project is to provide better personalized care to patients with T1D by understanding the mechanisms that are associated with protection against diabetic complications. This will add to our understanding on SGLT2 inhibitors and may provide useful for use in other patient groups as well as the T1D population.