Semaglutide Becomes First GLP-1 RA to Show 24% Reduction in Kidney Disease Progression Risk in Phase 3 FLOW Trial

On March 5, 2024, Novo Nordisk announced the main results of the large Phase 3 clinical trial FLOW.

The FLOW study aims to explore the efficacy and safety of semaglutide in treating diabetic nephropathy. Chronic kidney disease (CKD) is a common complication of type 2 diabetes, with approximately 40% of type 2 diabetes patients experiencing CKD.

The study enrolled a total of 3,533 patients with type 2 diabetes and CKD, who were randomly assigned in a 1:1 ratio to receive either semaglutide 1 mg or placebo.

The primary endpoint wasComposite Endpoint：

1. eGFR persistently decreases by ≥50%;

2. Reach ESRD (eGFR <15mL/min/1.73m²);

3. CKD or cardiovascular death.

Key Secondary EndpointIncluding: annual rate of change in eGFR, major adverse cardiovascular events (non-fatal myocardial infarction, non-fatal stroke, cardiovascular death), and all-cause mortality.

Source: Reference 1

The trial was initiated in 2019 and was originally scheduled to be completed by the end of 2024. However, in October last year, Novo Nordisk announced that, based on the interim analysis results, the independent Data Monitoring Committee (DMC) concluded that the interim analysis results of the clinical trial met certain pre-specified criteria.It is recommended to terminate the trial prematurely.。

The implication is that the efficacy is so remarkable that there's no point in wasting time; it wouldn't be fair to the patients in the placebo group either.

According to the recent announcement by Novo Nordisk, the FLOW trial met its primary endpoint, with patients receiving 1mg semaglutide treatment showingThe risk of kidney disease progression and cardiovascular and renal death was significantly reduced by 24%.The analysis showed that the risks of CKD and cardiovascular death in the composite primary endpoint were both reduced.

Moreover, the superiority of 1mg semaglutide over placebo was also confirmed in the confirmatory secondary endpoints. In terms of safety, 1mg semaglutide demonstrated good safety and tolerability, consistent with the results from previous trials.

Detailed results of the FLOW study are expected to be released at scientific conferences in 2024. Based on the results of the FLOW study, Novo Nordisk plans to submit a regulatory approval application for a new indication of Ozempic (semaglutide antidiabetic formulation) to the United States and the European Union in 2024.

Summary

As a phenomenal GLP-1 RA product, semaglutide has continuously broken through treatment fields on its own, driving the entire track to become highly popular.

Previously, semaglutide has demonstrated benefits in heart failure treatment (STEP HFpEF study) and reduction of cardiovascular event risks (SELECT study) through large-scale studies. Now expanding into the CKD field, it is not only expected to become the first GLP-1 RA in the diabetic nephropathy area but also achieves both cardiac and renal benefits for diabetes.

Given time, GLP-1 RA may encroach on all territories of SGLT-2 and become the true king of metabolism.