Risk Model Suggests SGLT2 Inhibitors Could Reduce CV, Renal Risk in Type 1 Diabetes

Using the Steno Type 1 Risk Engine, a team from Denmark conducted a study suggesting SGLT2 inhibition could lower risk of cardiovascular disease and end-stage kidney disease in patients with type 1 diabetes.

Data from a study presented at the American Society of Nephrology’s Kidney Week 2021 suggests sodium-glucose cotransporter 2 (SGLT2) inhibitors could have cardiorenal protective effects in adults with type 1 diabetes.

While the class has received attention for its effects in type 2 diabetes, and more recently patients without diabetes, the Kidney Week study used validated prediction models for cardiovascular disease and kidney failure in people with type 1 diabetes and determined use of SGLT2 inhibitors was associated with a 6% reduction in risk of cardiovascular disease and a 5.3% reduction in risk of kidney failure.

“In our study, we have shown significant risk reductions for cardiovascular disease and kidney failure with SGLT2 inhibitor treatment in type 1 diabetes,” said lead author Elisabeth Stougaard, MD, a PhD student in Complications Research at the Steno Diabetes Center, in Copenhagen, Denmark, in a statement. “Our model provides an estimate of benefit that may balance the risks associated with use of SGLT2 inhibitors in type 1 diabetes.”

As excitement surrounding the effects of SGLT2 inhibitors in major trials such as DAPA-CKD and EMPEROR-Preserved, interest in further exploration of the effects of the class has continued to grow at an incredible pace. With increased risk of cardiovascular and renal comorbidities not limited to patients with type 2 diabetes, Stougaard and a team of colleagues, including Peter Rossing, MD, DMSc, Head of Complications Research and Chief Physician at Steno Diabetes Center, sought to estimate the risk of cardiovascular disease and end-stage kidney disease in patients with type 1 diabetes with and without treatment with SGLT2 inhibitors.

To do so, investigators designed their study using the Steno Type 1 Risk Engine and data from a cohort of 3,660 adults with type 1 diabetes treated from 2001-2016 who were aged 30-75 years and an eGFR above 45 ml/min/1.73m2. Of note, the Steno Type 1 Risk Engine is a validated risk calculator built using clinical data from the electronic health records of the approximately 5,000 patients with type 1 diabetes treated at Steno Diabetes Center Copenhagen in combination with data from national registries designed to predict 5- and 10-year risks of nonfatal and fatal cardiovascular disease.

For the purpose of analysis, the effects of SGLT2 inhibition were simulated by changing the recorded HbA1c and systolic blood pressure values in accordance with results from the DEPICT studies. Individual absolute changes in HbA1c and systolic blood pressure were simulated as randomly drawn numbers from a normal distribution with a mean of -3.6 (SD, 0.9) mmol/mmol and -1.12 (SD, 2.8) mmHg. Additionally, the recorded eGFR and albuminuria were adjusted in accordance with results from the Tandem studies, with no change in eGFR and mean percentage change in albuminuria of -23.7 (SD, 12.9).

Upon analysis, results suggested use of SGLT2 inhibitors contributed to a change in risk variables that translated to an overall reduction in relative risk for 5-year cardiovascular of 6.1% (95% CI, 5.9-6.3), with this risk reduction reaching 11.1% (95% CI, 10.0-12.2) in a subgroup of patients with albuminuria. For end-stage kidney disease, the overall relative risk reduction observed for 5-year risk with SGLT2 inhibition was lowered by 5.3% (95% CI, 5.1-5.4), with this risk reduction reaching 7.6% in a subgroup of patients with albuminuria.

“Using the Steno T1 CVD and renal risk engine we estimated the risk of CVD and ESKD in persons with T1D with and without treatment with SGLT2i and found a substantial CVD and ESKD risk reduction, especially in the subgroup with albuminuria. Our model provides an estimate of benefit that may balance the risks associated with use of SGLT2 inhibition in T1D,” wrote investigators in their conclusion.

This study, “Sodium–glucose cotransporter 2 inhibitors as adjunct therapy for type 1 diabetes and the benefit on cardiovascular and renal disease evaluated by Steno risk engines,” was presented at Kidney Week 2021.