Sotagliflozin may offer cardiorenal protection for adults with T1D

Using the Steno T1 Risk Engines, the dual SGLT*1 and SGLT2 inhibitor sotagliflozin showed potential in reducing the risk of cardiovascular (CV) and renal disease in adults with type 1 diabetes (T1D).

“Sotagliflozin has demonstrated CV and kidney benefits in high-risk adults with T2D in the SCORED trial,” said Dr Elisabeth Stougaard from Steno Diabetes Center Copenhagen, Herlev, Denmark, at EASD 2022. “In T1D, sotagliflozin improves glycaemic control, reduced body weight and blood pressure, and increased time in range. However, this has also been associated with an increased risk of diabetic ketoacidosis (DKA).”

“Unfortunately, we have no CV and kidney outcome trials on the [effect of] SGLT inhibitors in T1D, and for now there is no prospect whether or not such trials will be performed in a T1D population,” Stougaard pointed out.

“If the cardiorenal benefits seen in T2D could be proven in T1D, these benefits might outweigh the risk of DKA,” she continued. As such, Stougaard and colleagues sought to assess the risk of CVD and end-stage kidney disease (ESKD) in adults with T1D treated with sotagliflozin by using the Steno T1 Risk Engine.

“[This engine is a] risk calculator for predicting 5- and 10-year risk of CVD and 5-year risk of ESKD,” said Stougaard. “[Using this risk engine, we found that] the estimated risk of CVD and ESKD was significantly reduced with sotagliflozin compared with placebo in [this group of patients].”

Patient-level data were used from three phase III inTandem trials (n=2,977; mean age 43 years, 50 percent male) wherein participants were randomized to once-daily placebo, sotagliflozin 200 mg, or sotagliflozin 400 mg for 24 weeks. Mean eGFR** is ~90 mL/min/1.73 m² while mean UACR*** is 7 mg/g. About 2 percent of the overall cohort had previous CVD. [EASD 2022, abstract 89]

At 24 weeks, sotagliflozin reduced the 5-year CVD risk, both with the 200-mg (mean percent difference, –4.85 percent) and the 400-mg dose (mean percent difference, –7.03 percent) as opposed to placebo. In the subgroup of participants with BMI ≥27 kg/m², the corresponding mean percent differences for both sotagliflozin doses were –3.04 percent and –7.20 percent, respectively.

“The risk reductions were quite similar for the 10-year CVD risk,” noted Stougaard.

For the 5-year ESKD risk, there were risk reductions for sotagliflozin 400 mg between –4.40 percent (patients with BMI ≥27 kg/m²) and –5.56 percent relative to placebo. The risk reductions for sotagliflozin 200 mg were insignificant, noted Stougaard.

“[Although our] study was based on a large population, reliable data, and a validated prediction model … this is not a real clinical trial,” Stougaard noted, stressing that the risks were calculated based on a risk engine.

The differences in study populations should also be taken into context, she added. The current trial had a low-risk population wherein only 2 percent had CVD and most participants had normal eGFR and UACR, compared with the SCORED trial wherein all participants had CVD and CKD.

“It is also worth mentioning that, while the greatest benefit of SGLT inhibitors has been on hospitalization for heart failure, this is not included in the risk engine, so we were not able to include this aspect,” she said.

“[Nonetheless,] our analysis provides additional clinical results that may positively enhance the risk-benefit assessment of sotagliflozin use in T1D,” Stougaard concluded.