FLOW Trial Analysis: Deep Dive into the SGLT2-GLP-1 Combination Therapy

American Diabetes Scientific Sessions, 24 June, 2024 – The FLOW trial (Novo Nordisk, NCT03819153), published in May 2024, investigated the effects of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1-RA), in patients with type 2 diabetes and chronic kidney disease. The results demonstrated a significant 24% reduction of the composite primary endpoint that included kidney outcomes and death due to cardiovascular and kidney causes. Additionally, semaglutide yielded positive effects on secondary endpoints, including a slower in estimated glomerular filtration rate (eGFR), an 18% reduction in major cardiovascular events, and a 20% decrease in all-cause mortality.

New data presented today at the ADA Scientific Sessions highlighted the interaction between SGLT2 inhibitor use at baseline and patient outcomes in the FLOW trial. The overall composite of kidney outcomes in patients receiving SGLT2i at baseline was not significantly different.  Changes in eGFR were seen both with and without combination of SGLT2 and GLP-1 however no additive effects were observed. (3.2 vs 3.7 ml/min/1.73m2 p-interaction=0.686).  Major adverse cardiovascular events were numerically lower in patients in patients on both SGLT2 inhibitors and placebo, as well as those receiving both SGLT2 inhibitors and semaglutide, compared to the group on neither medication. However, these were not significantly different (p-interaction=0.741) and indicate the need for further studies with larger patient populations.  Similar numerical differences trending in favour of the combination was also seen for all-cause mortality (p-interaction=0.901).

Underscoring the need for new treatment approaches, Dr. Richard E. Pratley, Medical Director at the AdventHealth Diabetes Institute Orlando, FL, and co-chair of the FLOW trial, stated, "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, Dr. Pratley suggests, "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."


Pratley RE. ADA 2024. FLOW: The First Dedicated CKD Outcomes Trial [Power Point Presentation].

American Diabetes Association. (2024, June 24). Semaglutide Reduced Risk for Major Kidney Disease Events by 24% for Patients with Type 2 Diabetes and Kidney Disease [Press release].

Perkovic V, et al. NEJM 2024. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. DOI: 10.1056/NEJMoa2403347

Mann JFE et al. Nat Med 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. DOI: 10.1038/s41591-024-03133-0