Quick answer
Extended answer
What was the FLOW trial?
Key facts
- Compound
- Semaglutide 1.0 mg SC weekly
- Design
- Randomised, double-blind, placebo-controlled
- Population
- 3,533 adults with T2D + CKD (elevated UACR)
- Primary outcome
- Composite: major kidney disease events + CV death
- Result
- Stopped early for efficacy at interim analysis
- Journal
- New England Journal of Medicine (2024)
- PMID
- 38785209
- DOI
- 10.1056/NEJMoa2403347
Background
SGLT2 inhibitors had established renal outcome benefit in chronic kidney disease with and without diabetes. GLP-1 receptor agonist renal outcome data prior to FLOW derived largely from secondary endpoints in cardiovascular trials. FLOW was designed as a dedicated renal outcomes trial.[5]
Study design
Randomised 1:1 to Semaglutide 1.0 mg weekly or matching placebo. Event-driven design. All participants received standard-of-care renal and cardiovascular management, including renin-angiotensin-system inhibition where clinically appropriate.
Population
3,533 adults with type 2 diabetes and CKD, defined by estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) thresholds. High-risk CKD population.
Primary outcomes
Primary composite: kidney failure (persistent eGFR < 15 ml/min/1.73 m², chronic kidney replacement therapy, or death from kidney failure), sustained ≥ 50% reduction in eGFR, or death from cardiovascular causes. The trial was stopped early for efficacy at a pre-planned interim analysis.[5]
Scientific significance
- First dedicated renal outcomes trial to demonstrate benefit for a GLP-1 receptor agonist in T2D-CKD.
- Complements SGLT2-inhibitor renal evidence rather than replacing it — the two classes act on different pathways.
- Extends the therapeutic rationale for GLP-1 receptor agonists in diabetic kidney disease.
Limitations
Research limitations
- Population was type 2 diabetes with CKD; extrapolation to CKD without diabetes is not direct.
- Early stopping for efficacy may inflate observed effect sizes relative to fully-completed trials.
- Absolute event rates and durability of eGFR-slope effects require continued follow-up.
- Interaction with concurrent SGLT2 inhibitor therapy in real-world practice is a topic of ongoing research.
Research-use framing
Related reading: Semaglutide monograph, Semaglutide research applications, SUSTAIN-6 and SELECT trial.
References5
- 1.
Marso SP, Bain SC, Consoli A, et al.. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes (SUSTAIN-6).. New England Journal of Medicine. 2016;375(19):1834-1844.
- 2.
Wilding JPH, Batterham RL, Calanna S, et al.. Once-weekly semaglutide in adults with overweight or obesity (STEP 1).. New England Journal of Medicine. 2021;384(11):989-1002.
- 3.
Davies M, Færch L, Jeppesen OK, et al.. Semaglutide 2·4 mg once a week in adults with overweight or obesity and type 2 diabetes (STEP 2).. Lancet. 2021;397(10278):971-984.
- 4.
Lincoff AM, Brown-Frandsen K, Colhoun HM, et al.. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT).. New England Journal of Medicine. 2023;389(24):2221-2232.
- 5.
Perkovic V, Tuttle KR, Rossing P, et al.. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes (FLOW).. New England Journal of Medicine. 2024;391(2):109-121.
Evidence summary
- What is Semaglutide?
Beginner-friendly research-focused introduction to Semaglutide — a long-acting GLP-1 receptor agonist derived from native GLP-1(7-37).
- Semaglutide Mechanism of Action
Receptor-level explanation of Semaglutide's activity at GLP-1R — Gαs / cAMP / PKA / EPAC2 signalling, β-arrestin recruitment, insulinotropic and glucagonostatic effects, gastric emptying and central appetite modulation.
- Semaglutide FAQ
Comprehensive research-focused FAQ on Semaglutide — identity, receptor pharmacology, structural modifications, pharmacokinetics, laboratory handling, evidence base and regulatory status.
- Semaglutide Pharmacokinetics
Reported pharmacokinetics of Semaglutide — half-life, albumin binding, C18 di-acid acylation, absorption for subcutaneous vs oral formulations, distribution, steady state and research limitations.
- Semaglutide Research Applications
Overview of published Semaglutide research contexts — metabolic, cardiovascular, renal, neuroinflammation/CNS and NAFLD/MASH — with a clear preclinical vs human evidence split.
- Albumin Binding and Half-Life Extension
Reusable mechanism guide explaining how fatty-acid acylation supports reversible non-covalent binding to serum albumin, and how that extends the plasma half-life of GLP-1 peptides.
Research use only
Publication information
- Published
- 2026-10-15
- Updated
- 2026-10-15
- Reviewed
- 2026-10-15
- Version
- 1.0
Revision history
- v1.02026-10-15· Editorial Team
Authority Sprint 2D — initial publication of GLP-1 foundation study summaries.
Editorial standards
Content is reviewed against our editorial process for scientific accuracy, sourcing, and clarity. Read our editorial standards.
Conflict of interest
Next scheduled review: 2028-04-15. Our research methodology describes how the review is conducted.