Effect of Semaglutide on Measured vs Estimated Glomerular Filtration Rate

Semaglutide is a glucagon-like peptide-1 receptor agonist widely used for its glucose-lowering effects in people with type 2 diabetes (T2D), as well as its cardiovascular and kidney-protective properties. However, it remains unclear whether semaglutide influences blood concentrations of endogenous filtration markers like creatinine, cystatin C, beta-trace protein (BTP), and beta-2 microglobulin (B2M). We investigated the effect of semaglutide on these filtration markers and the performance of estimated glomerular filtration rate (eGFR) equations compared with measured glomerular filtration rate (mGFR).

Post hoc analysis of a randomized, double-blind, placebo-controlled clinical trial. Individuals with T2D and albuminuria were randomized in a 1:1 ratio to receive semaglutide 1 mg weekly or matching placebo for 26 weeks on top of empagliflozin. mGFR was determined by 99m-Tc-DTPA plasma clearance and eGFR was calculated using CKD-EPI equations based on plasma creatinine (eGFRcre), cystatin C (eGFRcys), their combination (eGFRcomb), or a panel of creatinine, cystatin C, BTP, and B2M (eGFRpanel). Outcomes included change in filtration marker concentration, mGFR, and eGFR from baseline to end-of-treatment, as well as eGFR performance compared to mGFR at each timepoint.

Among 48 participants (median age 70 years; 16.7% female), semaglutide treatment was associated with a small but significant increase in plasma creatinine and BTP compared with placebo, whereas there was no significant change in cystatin C or B2M. Semaglutide treatment was not associated with a significant change in mGFR (median [IQR] change of 0 [-7.5 to 10.3] mL/min/1.73 m2) compared with placebo (median [IQR] change of -2 [-11.3 to 3.0] mL/min/1.73 m2). Both eGFRcre and eGFRcys were consistently outperformed by eGFRcomb and eGFRpanel at baseline and end-of-treatment.

Semaglutide treatment was associated with a small increase in plasma creatinine and BTP but not cystatin C or B2M, and eGFRcomb yielded the most reliable estimates of mGFR.