A Research Study to See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease

Summary

The researchers are doing this study to see if semaglutide can slow down the growth and worsening of chronic kidney disease in people with type 2 diabetes. Participants will get semaglutide (active medicine) or placebo ('dummy medicine'). This is known as participants' study medicine - which treatment participants get is decided by chance. Semaglutide is a medicine, doctors can prescribe in some countries for the treatment of type 2 diabetes. Participants will get the study medicine in a pen. Participants will use the pen to inject the medicine in a skin fold once a week. The study will close when there is enough information collected to show clear result of the study. The total time participants will be in this study is about 3 to 5 years, but it could be longer.

Timeline

Start

2019-06-17

Primary completion

2024-01-09

Completion

2024-01-09

Publications

• Background Rossing P, Baeres FMM, Bakris G, Bosch-Traberg H, Gislum M, Gough SCL, Idorn T, Lawson J, Mahaffey KW, Mann JFE, Mersebach H, Perkovic V, Tuttle K, Pratley R. The rationale, design and baseline data of FLOW, a kidney outcomes trial with once-weekly semaglutide in people with type 2 diabetes and chronic kidney disease. Nephrol Dial Transplant. 2023 Aug 31;38(9):2041-2051. doi: 10.1093/ndt/gfad009.
• Tuttle KR, Bakris GL, Baeres FMM, Bang CN, Bax WA, Belmar N, Musinga D, Cherney DZI, Chernin G, Lim SK, Mann JFE, Perkovic V, Pratley R, Ridker PM, Rossing P, Schmieder R, Shamkhalova MS, Sreenivasamurthy L, Mahaffey KW. Kidney and Survival Benefits of Semaglutide in Diabetes With Chronic Kidney Disease: FLOW Trial Cardiovascular Subgroup Analyses. J Am Coll Cardiol. 2026 Jun 2;87(21):2996-3012. doi: 10.1016/j.jacc.2026.02.5125.
• Rayner B, Mahaffey KW, Mann JFE, Pratley RE, Rossing P, Belmar N, Bosch-Traberg H, Jeppesen OK, Tran MC, Chernin G, Tuttle KR. Effect of semaglutide on COVID-19 and other infections: an analysis from the FLOW randomized clinical trial. Nephrol Dial Transplant. 2026 Feb 23:gfag036. doi: 10.1093/ndt/gfag036. Online ahead of print.
• Tuttle KR, Mann JFE, Mayrdorfer MM, Rayner B, Pugliese G, Pratley RE, Perkovic V, Mahaffey KW, Kashihara N, Jeppesen OK, Gumprecht J, Correa-Rotter R, Cherney DZI, Bosch-Traberg H, Arici M, Rossing P; FLOW Trial Investigators. Kidney and Survival Outcomes with Semaglutide by CKD Severity in the FLOW Trial. Clin J Am Soc Nephrol. 2026 Feb 18;21(5):841-51. doi: 10.2215/CJN.0000000974. Online ahead of print.
• Rossing P, Lindhardt M, Tikkanen CK, Menon J, Cattin J, Hunt B, Malkin SJP, Chubb B, Damgaard T, Borg R. Once-weekly semaglutide versus placebo for the treatment of type 2 diabetes and chronic kidney disease in Denmark: A long-term cost-effectiveness analysis based on FLOW. Cardiovasc Diabetol. 2025 Dec 20;25(1):32. doi: 10.1186/s12933-025-03002-1.
• Pruijm M, Belmar N, Bjornstad P, Cherney DZI, Das V, Gunnarsson T, Hodgin JB, Schytz PA, Tuttle KR, Kretzler M. REMODELing mechanistic trials for kidney disease: a multimodal, tissue-centered approach to understand the renal mechanism of action of semaglutide. Kidney Int. 2026 Jan;109(1):6-16. doi: 10.1016/j.kint.2025.10.005. Epub 2025 Nov 7.
• Natale P, Green SC, Tunnicliffe DJ, Pellegrino G, Toyama T, Strippoli GF. Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2025 Feb 18;2(2):CD015849. doi: 10.1002/14651858.CD015849.pub2.
• Mendonca L, Moura H, Chaves PC, Neves JS, Ferreira JP. The Impact of Glucagon-Like Peptide-1 Receptor Agonists on Kidney Outcomes: A Meta-Analysis of Randomized Placebo-Controlled Trials. Clin J Am Soc Nephrol. 2025 Feb 1;20(2):159-168. doi: 10.2215/CJN.0000000584. Epub 2024 Oct 8.
• Kosiborod MN, Deanfield J, Pratley R, Borlaug BA, Butler J, Davies MJ, Emerson SS, Kahn SE, Kitzman DW, Lingvay I, Mahaffey KW, Petrie MC, Plutzky J, Rasmussen S, Ronnback C, Shah SJ, Verma S, Weeke PE, Lincoff AM; SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM Trial Committees and Investigators. Semaglutide versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: a pooled analysis of the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM randomised trials. Lancet. 2024 Sep 7;404(10456):949-961. doi: 10.1016/S0140-6736(24)01643-X. Epub 2024 Aug 30.
• Pratley RE, Tuttle KR, Rossing P, Rasmussen S, Perkovic V, Nielsen OW, Mann JFE, MacIsaac RJ, Kosiborod MN, Kamenov Z, Idorn T, Hansen MB, Hadjadj S, Bakris G, Baeres FMM, Mahaffey KW; FLOW Trial Committees and Investigators. Effects of Semaglutide on Heart Failure Outcomes in Diabetes and Chronic Kidney Disease in the FLOW Trial. J Am Coll Cardiol. 2024 Oct 22;84(17):1615-1628. doi: 10.1016/j.jacc.2024.08.004. Epub 2024 Aug 30.
• Mann JFE, Rossing P, Bakris G, Belmar N, Bosch-Traberg H, Busch R, Charytan DM, Hadjadj S, Gillard P, Gorriz JL, Idorn T, Ji L, Mahaffey KW, Perkovic V, Rasmussen S, Schmieder RE, Pratley RE, Tuttle KR. Effects of semaglutide with and without concomitant SGLT2 inhibitor use in participants with type 2 diabetes and chronic kidney disease in the FLOW trial. Nat Med. 2024 Oct;30(10):2849-2856. doi: 10.1038/s41591-024-03133-0. Epub 2024 Jun 24.
• De La Flor JC, Moral E, Deira J, Monzon T, Valga F, Albarracin C, Rodeles M. Response to "Experience with dulaglutide in an obese diabetic patient on incremental peritoneal dialysis". Response to related letter. Nefrologia (Engl Ed). 2024 May-Jun;44(3):444-446. doi: 10.1016/j.nefroe.2023.10.010. Epub 2024 Jun 10. No abstract available.
• Perkovic V, Tuttle KR, Rossing P, Mahaffey KW, Mann JFE, Bakris G, Baeres FMM, Idorn T, Bosch-Traberg H, Lausvig NL, Pratley R; FLOW Trial Committees and Investigators. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. N Engl J Med. 2024 Jul 11;391(2):109-121. doi: 10.1056/NEJMoa2403347. Epub 2024 May 24.
• Cohen S, Sternlicht H, Bakris GL. Mineralocorticoid Receptor Antagonists in the Treatment of Diabetic Kidney Disease: Their Application in the Era of SGLT2 Inhibitors and GLP-1 Receptor Agonists. Curr Diab Rep. 2022 May;22(5):213-218. doi: 10.1007/s11892-022-01461-4. Epub 2022 Apr 20.

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Indications