Impact of Oral Semaglutide on Kidney Outcomes in People With Type 2 Diabetes: Results From the SOUL Randomized Trial.

Summary

In 9,650 adults with T2D and ASCVD/CKD followed for 47.5 months, oral semaglutide did not significantly reduce prespecified kidney composite outcomes versus placebo but significantly slowed annual eGFR decline by 0.40 mL/min/1.73 m2. Benefits were consistent across subgroups, including baseline eGFR <60.

Key Findings

• No significant reduction in five-point (HR 0.91; P=0.19) or four-point kidney composite outcomes (HR 0.86; P=0.22).
• Significant attenuation of annual eGFR decline by 0.40 mL/min/1.73 m2 (P<0.0001).
• Effects were consistent across subgroups, including baseline eGFR <60 mL/min/1.73 m2.
• Serious adverse events were similar between groups.

Clinical Implications

Oral semaglutide may be considered to slow eGFR decline in T2D with ASCVD/CKD, while SGLT2 inhibitors remain essential for hard kidney outcome reduction. Patient counseling should distinguish eGFR slope benefits from composite event risk.

Limitations

• Participants had mostly preserved eGFR, limiting kidney event rates and power for hard outcomes
• Trial not primarily powered for kidney composites

Future Directions

Assess oral semaglutide’s renal effects in populations with lower eGFR and higher albuminuria, and evaluate combination with SGLT2 inhibitors for additive kidney protection.