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FLOW trial demonstrates kidney, cardiovascular benefits of semaglutide in high-risk patients with type 2 diabetes


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Findings from the FLOW trial, the first-ever dedicated kidney outcomes trial with a glucagon-like peptide-1 (GLP-1) receptor agonist, demonstrated that semaglutide slowed progression of kidney disease in people with type 2 diabetes and improved both kidney outcomes and cardiovascular mortality. The findings were presented by a panel of investigators during a symposium on Monday, June 24, at the 84th Scientific Sessions and simultaneously published in Nature Medicine.

Katherine R. Tuttle,MD, FACP, FASN, FNKF
Katherine R. Tuttle, MD, FACP, FASN, FNKF

“There are currently 537 million people worldwide with diabetes, and kidney disease remains one of the most common and devastating complications, occurring in four of 10 with type 2 diabetes and three of 10 with type 1, making it responsible for half of all chronic kidney disease (CKD) in the world,” said Katherine R. Tuttle, MD, FACP, FASN, FNKF, University of Washington, who summarized the main findings of the FLOW trial and the potential clinical implications.

“While our traditional focus has been on progression to kidney failure, there are actually a preponderance of people who are lost to death, particularly due to cardiovascular causes,” Dr. Tuttle said. “So, our focus on risk reduction for people with diabetes and CKD must be holistic and focus not only on risk of kidney failure, but on cardiovascular outcomes and mortality.”

The double-blind, randomized, placebo-controlled international trial enrolled 3,533 participants with a median follow-up period of 3.4 years. The trial compared injectable semaglutide (1.0 mg) once weekly with a placebo as an adjunct to the standard of care for the prevention of major kidney outcomes, specifically kidney failure, substantial loss of kidney function, and death from kidney or cardiovascular causes.

Investigators reported that participants who received semaglutide experienced a 24 percent risk reduction of the composite primary endpoint, including kidney outcomes and death due to cardiovascular and kidney causes, compared to those who received a placebo. In addition, the secondary endpoints showed significant improvements with semaglutide, including a slower estimated glomerular filtration rate (eGFR), a reduction of major cardiovascular events by 18 percent, and a reduction of the risk of all-cause death by 20 percent. The trial was stopped early for clear positive efficacy with a hazard ratio for the primary kidney outcome of 0.76.

“There are four pillars of therapy now for people with CKD and diabetes—a conventional angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB), a sodium-glucose cotransporter-2 (SGLT2) inhibitor, the non-steroidal mineralocorticoid antagonist finerenone, and now semaglutide, which shows consistent benefits across groups and in different forms of analysis,” Dr. Tuttle said.

Moving forward, the focus now must turn to awareness and implementation and improving processes of care, including goals of risk factor management, she said.

“We know that semaglutide saves kidneys, hearts, and lives,” Dr. Tuttle said. “However, low awareness, detection, and access to care are major barriers to receiving kidney, heart, and life-saving therapies. Our challenge now is effective strategies for implementation to really deliver on the promise of improving clinical outcomes for people with type 2 diabetes and CKD.”

Other speakers during the symposium included:

  • Peter Rossing, MD, DMSc, Steno Diabetes Center Copenhagen, Denmark, who discussed the FLOW trial rationale.
  • Richard E. Pratley, MD, AdventHealth, who described the FLOW trial design and baseline characteristics of the study participants.
  • Vlado Perkovic, MBBS, PhD, FRACP, FASN, FAHMS, University of New South Wales, Australia, who shared the FLOW trial kidney outcomes.
  • Kenneth W. Mahaffey, MD, PhD, Stanford University Center for Clinical Research, who discussed the FLOW trial cardiovascular outcomes.
  • Johannes F.E. Mann, MD, Professor of Medicine, Friedrich Alexander University Erlangen, Germany, who described the FLOW results by baseline use of SGLT2 inhibitors.
  • Sylvia Rosas, MD, MSCE, Joslin Diabetes Center, who concluded the symposium with an independent commentary of the FLOW trial findings.

The symposium The First Dedicated Kidney Outcome Trial with a GLP-1 Receptor Agonist Once-Weekly Semaglutide and the FLOW Trial Results can be viewed on-demand by registered meeting participants on the virtual meeting platform. If you haven’t registered for the 84th Scientific Sessions, register today to access the valuable meeting content through Aug. 26.