Effects of GLP-1RA on top of SGLT2 inhibitor on albuminuria in patients with T2D and albuminuria

EASD 2023 A small randomized study showed that treatment with GLP-1RA semaglutide on top of empagliflozin did not have an additional beneficial effect on albuminuria in patients with T2D and albuminuria compared with placebo.

Presented at the EASD annual meeting 2023 by: Suvanjaa Sivalingam, MD - Copenhagen, Denmark

Introduction and methods

SGLT2 inhibitors have demonstrated to protect the kidneys in patients with T2D and/or CKD. GLP-1RA may also have potential protective effects on kidney outcomes, but a dedicated kidney outcome study is still ongoing. The aim of the current study was to investigate if the addition of semaglutide on top of empagliflozin would complement or have an additive effect on kidney function compared with placebo.

This was a randomized, placebo-controlled trial in which 73 patients with T2D and albuminuria entered a run-in phase of 26 weeks with empagliflozin 25 mg once daily. After the run-in phase, patients (n=60) were randomized to the addition of semaglutide 1 mg once weekly or placebo on top of ongoing empagliflozin therapy for 26 weeks. Key inclusion criteria were: eGFR >30 ml/min/1.73 m²; UACR >100 mg/g; and stable RAAS blocker treatment. The primary endpoint was change in albuminuria from randomization to end of study. Secondary endpoints were changes in eGFR, HbA1c, body weight, 24-h systolic blood pressure, and RAAS hormones. In the analysis, there was data available of 26 patients in the placebo group and 28 patients in the semaglutide group.

Main results

• The addition of semaglutide on top of empagliflozin did not reduce albuminuria compared with placebo (difference in UCAR between treatment groups: -22 mg/g; 95%CI: -44 to 10; P=0.154).
• Treatment with semaglutide on top of empagliflozin reduced HbA1c (-8 mmol/mol; 95%CI: -13 to -3; P=0.003) and plasma aldosterone levels (-30 pmol/L; 95%CI: -50 to -3; P=0.035) compared with placebo.
• There were no changes in eGFR, 24-h systolic blood pressure, body weight, and plasma renin levels between treatment groups.

Conclusion

The addition of semaglutide on top of empagliflozin did not reduce albuminuria compared with treatment with empagliflozin alone in patients with T2D and albuminuria in this small randomized study. Combination therapy with semaglutide and empagliflozin did not change measured eGFR, 24-h systolic blood pressure, body weight or plasma renin levels, but it did reduce HbA1c and plasma aldosterone levels compared with placebo. It should be noted that sample size calculation was amended during the study period due to recruitment challenges, which might have impacted the statistical power of the study.

- Our reporting is based on the information provided at the EASD annual meeting -

The results of this study have recently been published in Diabetes Obes Metab.