Kidney Outcomes with Sodium-glucose co-transporter-2 Inhibitors (SGLT2i) in Patients with type 2 diabetes (T2D) and Atherosclerotic cardiovascular disease (ASCVD): Insights from the VERTIS-CV Study within the SMART-C Framework

Diabetes is a disease that occurs when blood glucose (sugar) levels are too high. Glucose is your body's main source of energy and comes from the food you eat, as well as from the body’s own production. Insulin is a hormone made by the pancreas that helps glucose enter the cells to be used for energy. When the body doesn't make enough insulin or doesn't use it effectively, glucose builds up in the blood, leading to diabetes.

Diabetes is a growing public health issue, affecting over 463 million adults worldwide. There are three main types of diabetes: type 1 diabetes (T1D), type 2 diabetes (T2D), and gestational diabetes. T1D occurs when the pancreas produces little or no insulin. T2D, the most common form, occurs when the body becomes resistant to insulin or doesn't produce enough. Gestational diabetes is high blood sugar that develops during pregnancy and typically resolves after childbirth.

T2D is associated with a higher risk of early death compared to the general population. Two major causes of reduced life expectancy in people with T2D are cardiovascular disease (CVD) and chronic kidney disease (CKD). Because many people with T2D also have both heart and kidney problems, it is essential to develop tools that help prevent these serious complications.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of prescription medicines used to lower blood sugar in adults with T2D, alongside diet and exercise. These drugs work by helping the kidneys remove excess sugar from the body through urine. One such medicine is ertugliflozin, which is the specific SGLT2 inhibitor used in the VERTIS-CV study. Large clinical trials have shown that SGLT2 inhibitors not only lower blood sugar but also reduce the risk of heart disease and slow kidney disease progression in people with T2D, heart failure, or CKD.

The proposed project will use data from the VERTIS-CV study to examine how ertugliflozin affects serious kidney outcomes in people with T2D and CVD. These outcomes include significant decline in kidney function, kidney failure, death from kidney-related causes, and severe kidney injury. This analysis is part of a larger effort to better understand the impact of SGLT2 inhibitors on kidney health across different patient populations.

The project is being conducted in collaboration with the SGLT2 Inhibitor Meta-Analysis Cardio-Renal Trialists’ Consortium (SMART-C), which was established in 2022 to combine data from major outcome trials. The ultimate goal of this work is to provide clear, reliable evidence about the benefits of SGLT2 inhibitors in various groups of patients. This will help improve clinical guidelines and support more personalized treatment for people with T2D. Results from this study may also inform the use of SGLT2 inhibitors in other patient populations and contribute to improved care for millions of people living with diabetes.