Promising Data from the First Dedicated Kidney Outcomes Trial with GLP-1 Receptor Agonist, Semaglutide, in Patients with Type 2 Diabetes and Chronic Kidney Disease

On 11 September 2024, the latest results from the FLOW trial were presented at the European Association for the Study of Diabetes (EASD) conference in Madrid, Spain. The FLOW trial, initiated in 2019, was a global, multinational, randomized controlled trial conducted across 28 countries, 387 sites, and 3,533 participants. Adults with type 2 diabetes (T2D) and chronic kidney disease (CKD) were randomized in a 1:1 ratio to receive either once-weekly semaglutide 1.0 mg alongside standard care or a placebo with standard care.

CKD is common among adults with T2D, and both GLP-1 receptor agonists (GLP-1RAs) and SGLT-2i have shown benefits in reducing cardiovascular and kidney events. The combined effect of these medication classes is still unclear. The FLOW trial recently assessed the impact of semaglutide, a GLP-1RA, in patients with and without SGLT-2i use at baseline. While cardiovascular outcome trials suggest that GLP-1RAs like semaglutide might improve kidney-related outcomes, dedicated kidney trials such as FLOW are essential to confirm these renoprotective effects.

Key Highlights:

• Semaglutide decreased the risk of the composite primary kidney outcome by 24%. Moreover, the effects of the drug independent of clinically relevant subgroups, i.e. sex, age, BMI, diabetes duration, or HbA1c; and different background medications, such as insulin, metformin, or SGLT2 inhibitors.
• Additionally, semaglutide reduced the decline in eGFR by 1.16 mL/min/1.73 m² per year and decreased urine albumin-to-creatinine ratio (UACR) by 32% compared to placebo.
• The drug significantly decreased the risk of major adverse cardiovascular events (MACEs) by 18% and reduced all-cause mortality by 20%, compared to placebo.
• The semaglutide group experienced fewer serious adverse events compared to placebo (49.6% versus 53.8%), but more adverse events leading to discontinuation (13.2% versus 11.9%).

Conclusion:

“This is a patient population at high-risk of severe kidney outcomes. Despite existing treatment options, there is still a clear unmet need for this group. The findings from the FLOW trial 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.”

AdventHealth Diabetes Institute, US

The FLOW trial demonstrated that once-weekly semaglutide 1.0 mg significantly improved kidney and cardiovascular outcomes in patients with T2D and CKD, reducing the risk of major kidney events by 24%, slowing eGFR decline, and decreasing UACR. It also lowered major adverse cardiovascular events and all-cause mortality, with a generally favorable safety profile. These findings highlight semaglutide’s effectiveness in enhancing both renal and cardiovascular health in this high-risk population. Further studies are needed to explore its potential benefits for individuals with CKD who do not have T2D.

Novo Nordisk intends to seek regulatory approvals in the US and EU for a label expansion of OZEMPIC (semaglutide) in 2024, based on the results of the FLOW trial. Moreover, the positive outcomes from this trial highlight semaglutide’s potential to become the first GLP-1 treatment option for people living with T2D and CKD.