German Study Finds Oral Semaglutide Slows Kidney Function Decline in Type 2 Diabetes

A study from Germany has found that the oral form of semaglutide — the active ingredient in medications like Ozempic and Rybelsus — may help protect kidney function in people with type 2 diabetes (T2D) who also have heart disease or chronic kidney disease (CKD), even if it didn't dramatically cut the risk of serious kidney events overall.

What Makes This International Research Valuable for US Patients

Germany's KfH Kidney Center in Munich is one of Europe's premier institutions for kidney disease research, and this trial enrolled nearly 10,000 participants across multiple countries — giving it statistical power that few studies achieve. For the estimated 37 million Americans living with diabetes, and the 1 in 3 diabetic Americans who will develop kidney disease, findings from this large global trial carry real weight when evaluating treatment options available right now in the US.

About the SOUL Trial

The SOUL trial (NCT03914326) was a rigorous double-blind, randomized controlled study comparing oral semaglutide against a placebo in 9,650 people with T2D who also had atherosclerotic cardiovascular disease (ASCVD), CKD, or both. Participants were followed for an average of nearly four years (47.5 months).

Researchers focused on kidney outcomes, including a drop of 50% or more in estimated glomerular filtration rate (eGFR) — a key measure of how well the kidneys filter blood — as well as the need for dialysis or kidney transplant, and death from kidney or cardiovascular causes.

Key Findings: What the Numbers Mean

The average participant entered the study with an eGFR of 73.8 mL/min/1.73 m², indicating mostly preserved — but not perfect — kidney function. In US clinical terms, this places most participants in CKD Stage 2 to early Stage 3.

The headline finding: oral semaglutide did not significantly reduce the composite of major kidney events (HR 0.91; P = 0.19). However, the drug did produce a statistically significant and clinically meaningful slowing of kidney function decline:

• Oral semaglutide group: eGFR declined an average of 1.67 mL/min/1.73 m² per year
• Placebo group: eGFR declined an average of 2.06 mL/min/1.73 m² per year
• Difference: 0.40 mL/min/1.73 m² per year preserved (P < 0.0001)

This effect was consistent in patients with worse kidney function at baseline (eGFR below 60 mL/min/1.73 m²), and serious side effects occurred at similar rates in both groups.

How This Compares to US Guidelines

Current American Diabetes Association (ADA) guidelines already recommend GLP-1 receptor agonists like semaglutide for people with T2D and CKD, particularly for their cardiovascular benefits. Injectable semaglutide (Ozempic) has previously shown kidney-protective effects in the FLOW trial. This German-led research adds important new evidence that the oral form (Rybelsus) — often preferred by patients who avoid injections — also slows kidney deterioration, supporting its use in this high-risk population.

Why This Matters for US Patients

Kidney disease is one of the most serious and costly complications of type 2 diabetes. Once kidney function is lost, it cannot be recovered. A treatment that slows the annual rate of kidney decline — even modestly — can potentially add years before a patient needs dialysis or a transplant. For Americans already taking oral semaglutide (Rybelsus) for blood sugar or heart protection, this study suggests they may be getting an important kidney benefit as well. Patients with T2D and any signs of kidney disease should discuss this research with their care team when reviewing their medication plan.

Study Citation

Mann J, Marx N, Deanfield J, et al. Impact of Oral Semaglutide on Kidney Outcomes in People With Type 2 Diabetes: Results From the SOUL Randomized Trial. Diabetes Care. 2026. DOI: 10.2337/dc25-1080. PMID: 41380027.