Semaglutide Shines in Kidney Health Across Diabetes Patients: Study Highlights Consistency and Potential

The study, published in Nature Medicine, revealed the benefits of semaglutide in reducing kidney outcomes were consistent in participants with/without using baseline sodium-glucose co-transporter-2 inhibitors (SGLT2i); power was limited for detecting smaller but clinically relevant effects.

Type 2 diabetes (T2D) often leads to complications such as CKD, which can severely impact kidney function over time. People with T2D and CKD have a high risk for kidney failure and cardiovascular (CV) complications. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has shown efficacy in controlling blood sugar levels and promoting weight loss in diabetic patients. SGLT2 inhibitors, on the other hand, help lower blood glucose levels by promoting urinary glucose excretion.

GLP-1 receptor agonists and SGLT2 inhibitors independently reduce cardiovascular and kidney events. There is no clarity on the effect of combining both. Considering this, Johannes F. E. Mann, University Hospital Erlangen, Friedrich Alexander University, Erlangen, Germany, and colleagues conducted the FLOW trial comprising participants with T2D and CKD who were stratified by baseline SGLT2i use (N = 550) or no use (N = 2,983) and randomized to semaglutide/placebo. The primary outcome was a composite of ≥50% eGFR reduction, kidney failure, and kidney or cardiovascular death.

The study led to the following findings:

• The risk of the primary outcome was 24% lower in all participants treated with semaglutide vs placebo.
• The primary outcome occurred in 41/277 (semaglutide) versus 38/273 (placebo) participants on SGLT2i at baseline (HR 1.07) and in 290/1,490 versus 372/1,493 participants not taking SGLT2i at baseline (HR 0.73).
• Three confirmatory secondary outcomes were predefined.
• Treatment differences favoring semaglutide for total eGFR slope (ml/min/1.73m2/year) were 0.75 in the SGLT2i subgroup and 1.25 in the non-SGLT2i-subgroup.
• Semaglutide benefits on major cardiovascular events and all-cause death were similar regardless of SGLT2i use.

FLOW trial findings have the potential to change the disease course of these high-risk patients and pave the way for new treatment strategies, offering hope to millions of patients globally.

In conclusion, the FLOW trial has underscored the promising role of semaglutide in managing type 2 diabetes and chronic kidney disease. As researchers delve deeper into these findings, there is optimism that this dual therapy approach could significantly improve outcomes and quality of life for patients battling these interconnected conditions.

Reference:

Mann, J. F., Rossing, P., Bakris, G., Belmar, N., Busch, R., Charytan, D. M., Hadjadj, S., Gillard, P., Górriz, J. L., Idorn, T., Ji, L., Mahaffey, K. W., Perkovic, V., Rasmussen, S., Schmieder, R. E., Pratley, R. E., & Tuttle, K. R. (2024). Effects of semaglutide with and without concomitant SGLT2 inhibitor use in participants with type 2 diabetes and chronic kidney disease in the FLOW trial. Nature Medicine, 1. https://doi.org/10.1038/s41591-024-03133-0