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Trial · Interventional

CompletedPhase 3Results postedRegistry data

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

Short name FLOW

NCTNCT03819153 (opens ClinicalTrials.gov in a new tab)Other idNN9535-4321Other idU1111-1217-6259Other id2018-002878-50Other idJapicCTI-194843
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 3
Enrollment
3,533 participants (actual)
Sponsor
Novo Nordisk A/S · Industry
Design
Randomized · Quadruple masking
Countries
28 countries

United States, Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, China, France, Germany, Greece, Hungary, India, Israel, Italy, Japan, Malaysia, Mexico, Netherlands, Poland, Russia, Slovakia, South Africa, Spain, Thailand, Turkey (Türkiye), Ukraine, United Kingdom

Start
17 Jun 2019
Primary completion
9 Jan 2024
Completion
9 Jan 2024
First posted
28 Jan 2019
Last update posted
20 Mar 2025
Conditions
Diabetes Mellitus, Type 2

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2019202020212022202320242025
  1. Ph 3

    FLOW

    NCT03819153

    17 Jun 2019 to 9 Jan 2024

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • SemaglutideDrug
  • Placebo (semaglutide)Drug

Arms2

  • Experimental

    Semaglutide

    Participants are to receive semglutide for up to 5 years or more (event driven). The trial is event driven with a pre-defined minimum number of renal endpoint events for the primary endpoint.

  • Placebo comparator

    Placebo

    Participants are to receive placebo (semglutide) for up to 5 years or more (event driven). The trial is event driven with a pre-defined minimum number of renal endpoint events for the primary endpoint.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Number of Participants From Time of Randomization to First Occurrence of Onset of Persistent ≥50% Reduction in eGFR(CKD-EPI); Onset of Persistent eGFR(CKD-EPI) <15mL/Min/1.73m^2; Initiation of Chronic Renal Replacement Therapy; Renal Death; CV Death

    Time frame · From Week 0 up to Week 234

    Registry description

    Number of participants with first composite renal event i.e., from time of randomization to first occurrence of an onset of persistent greater than or equal to (≥) 50 percent (%) reduction in estimated glomerular filtration rate (eGFR) (chronic kidney disease - epidemiology collaboration \[CKD-EPI\]), onset of persistent eGFR (CKD-EPI) \<15 milliliter per minute per 1.73 meter square (mL/min/1.73m\^2), initiation of chronic renal replacement therapy (dialysis or kidney transplantation), renal death, and cardiovascular (CV) death combined data were reported in this outcome measure.

Secondary outcomes(20)

  1. Annual Rate of Change in eGFR (CKD-EPI) (Total eGFR Slope)

    Time frame · From Week 0 up to Week 234

    Registry description

    Annual rate of change in Total eGFR slope CKD-EPI were reported from baseline at Week 234 in-trial period. eGFR was calculated using the CKD-EPI formula. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.

  2. Number of Participants From Time of Randomization to Occurrence of Onset of Persistent ≥50% Reduction in eGFR (CKD-EPI)

    Time frame · From Week 0 up to Week 234

    Registry description

    Number of participants from time of randomization to time to occurrence of onset of persistent ≥50% reduction in eGFR (CKD-EPI) were reported. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.

  3. Number of Participants From Time of Randomization to Occurrence of Onset of Persistent eGFR (CKD-EPI) <15mL/Min/1.73m^2

    Time frame · From Week 0 up to Week 234

    Registry description

    Number of participants from time of randomization to time to occurrence of onset of persistent eGFR (CKD-EPI) \<15 mL/min/1.73m\^2 were reported. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.

  4. Number of Participants From Time of Randomization to Occurrence of Initiation of Chronic Renal Replacement Therapy

    Time frame · From Week 0 up to Week 234

    Registry description

    Number of participants from time of randomization to time to occurrence of initiation of chronic renal replacement therapy (dialysis or kidney transplantation) were reported. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.

  5. Number of Participants From Time of Randomization to Occurrence of Renal Death

    Time frame · From Week 0 up to Week 234

    Registry description

    Number of participants from time of randomization to time to occurrence of renal death were reported. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.

  6. Number of Participants From Time of Randomization to Occurrence of CV Death

    Time frame · From Week 0 up to Week 234

    Registry description

    Number of participants from time of randomization to time to occurrence of CV death were reported. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.

  7. Annual Rate of Change in eGFR (Chronic Kidney Disease CKD-EPI) (Chronic eGFR Slope)

    Time frame · Week 12, Week 234

    Registry description

    Annual rate of change in eGFR in terms of chronic kidney disease CKD-EPI were reported from Week 12 to Week 234 in-trial period. eGFR was calculated using the CKD-EPI formula. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.

  8. Change From Baseline in eGFR (CKD-EPI) at Week 12

    Time frame · Baseline (Week 0), Week 12

    Registry description

    Change from baseline in eGFR at Week 12 during in-trial period were reported. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.

  9. Change From Baseline in eGFR (Cystatin C CKD-EPI) at Week 104

    Time frame · Baseline (Week 0), Week 104

    Registry description

    Changes from baseline in eGFR (cystatin C) at Week 104 in-trial period were reported. Cystatin C was calculated using the CKD-EPI formula. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.

  10. Change From Baseline in Urinary Albumin-to-creatinine Ratio (UACR) at Week 104: Ratio to Baseline

    Time frame · Baseline (Week 0), Week 104

    Registry description

    Change from baseline in UACR (ratio to baseline) at Week 104 in-trial period were reported. For UACR, the baseline assessment is defined as the mean of the two assessments from the randomization visit. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.

  11. Number of Participants From Time of Randomization to Time to First Occurrence of a Major Adverse Cardiovascular Event (MACE): Acute Myocardial Infarction (Non Fatal); Non-fatal Stroke; and CV Death

    Time frame · From Week 0 up to Week 234

    Registry description

    Number of participants who reported first occurence of non-fatal acute myocardial infarction, non-fatal stroke, and CV death combined data were presented from Week 0 up to Week 234 during on-treatment period. MACE consisted of non-fatal acute myocardial infarction, cardiovascular death and non-fatal stroke. First on-treatment period is defined as period from date of first dose until first time where no dose had been administered within 5 weeks (35 days) or end of the in-trial period, whichever came first.

  12. Number of Participants From Time of Randomization to Time to Occurrence of All-cause Death

    Time frame · From Week 0 up to Week 234

    Registry description

    Number of participants who reported occurence of deaths from Week 0 up to Week 234 during in-trial period were presented. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.

  13. Number of Participants From Time of Randomization to Time to Occurrence of Each of the Individual Components of the Confirmatory Secondary MACE Endpoint: Non-fatal Myocardial Infarction

    Time frame · From Week 0 up to Week 234

    Registry description

    Number of participants who reported occurrence of non-fatal acute myocardial infarction from Week 0 up to Week 234 during in-trial period were presented. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.

  14. Number of Participants From Time of Randomization to Time to Occurrence of Each of the Individual Components of the Confirmatory Secondary MACE Endpoint: Non-fatal Stroke

    Time frame · From Week 0 up to Week 234

    Registry description

    Number of participants who reported occurrence of non-fatal stroke from Week 0 up to Week 234 during in-trial period were presented. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.

  15. Number of Participants From Time of Randomization to Time to First Occurrence of Major Adverse Limb Events (MALE): Acute Limb Ischaemia Hospitalization and Chronic Limb Ischaemia Hospitalization

    Time frame · From Week 0 up to Week 234

    Registry description

    Number of participants with combined data of first occurence of acute limb ischaemia hospitalization and chronic limb ischaemia hospitalization from Week 0 up to Week 234 during on-treatment period were presented. MALE consisted of acute and chronic limb ischaemia hospitalisation.

  16. Number of Participants With Acute Limb Ischaemia Hospitalization and Chronic Limb Ischaemia Hospitalization

    Time frame · From Week 0 up to Week 234

    Registry description

    Number of participants of acute limb ischaemia hospitalization and chronic limb ischaemia hospitalization from Week 0 up to Week 234 during in-trial period were presented. MALE consisted of acute and chronic limb ischaemia hospitalisation. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.

  17. Change From Baseline in Body Weight at Week 104

    Time frame · Baeline (Week 0), Week 104

    Registry description

    Change in body weight from Week 0 up to Week 104 during in-trial period, measured in kilograms, were presented. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.

  18. Change From Baseline in Glycosylated Haemoglobin (HbA1c) at Week 104

    Time frame · Baseline (Week 0), Week 104

    Registry description

    Change in HbA1c from Week 0 to Week 104 during in-trial period, measured in percentage point of HbA1c, were presented. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.

  19. Change From Baseline in Systolic Blood Pressure at Week 104

    Time frame · Baseline (Week 0), Week 104

    Registry description

    Change in systolic blood pressure from Week 0 to Week 104 during in-trial period were presented. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.

  20. Change From Baseline in Diastolic Blood Pressure at Week 104

    Time frame · Baseline (Week 0), Week 104

    Registry description

    Change in diastolic blood pressure from Week 0 to Week 104 during in-trial period were reported. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeCount of participants· From Week 0 up to Week 234

Number of Participants From Time of Randomization to First Occurrence of Onset of Persistent ≥50% Reduction in eGFR(CKD-EPI); Onset of Persistent eGFR(CKD-EPI) <15mL/Min/1.73m^2; Initiation of Chronic Renal Replacement Therapy; Renal Death; CV Death

GroupValue (Participants)
Semaglutide331
Placebo410
Secondary and other outcome results(7)
Secondary outcomeMean· From Week 0 up to Week 234

Annual Rate of Change in eGFR (CKD-EPI) (Total eGFR Slope)

GroupValue ((mL/min/1.73 m^2)/year)Spread
Semaglutide-2.190.1
Placebo-3.360.1
Secondary outcomeCount of participants· From Week 0 up to Week 234

Number of Participants From Time of Randomization to Occurrence of Onset of Persistent ≥50% Reduction in eGFR (CKD-EPI)

GroupValue (Participants)
Semaglutide165
Placebo213
Secondary outcomeCount of participants· From Week 0 up to Week 234

Number of Participants From Time of Randomization to Occurrence of Onset of Persistent eGFR (CKD-EPI) <15mL/Min/1.73m^2

GroupValue (Participants)
Semaglutide92
Placebo110
Secondary outcomeCount of participants· From Week 0 up to Week 234

Number of Participants From Time of Randomization to Occurrence of Initiation of Chronic Renal Replacement Therapy

GroupValue (Participants)
Semaglutide87
Placebo100
Secondary outcomeCount of participants· From Week 0 up to Week 234

Number of Participants From Time of Randomization to Occurrence of Renal Death

GroupValue (Participants)
Semaglutide5
Placebo5
Secondary outcomeCount of participants· From Week 0 up to Week 234

Number of Participants From Time of Randomization to Occurrence of CV Death

GroupValue (Participants)
Semaglutide123
Placebo169
Secondary outcomeMean· Week 12, Week 234

Annual Rate of Change in eGFR (Chronic Kidney Disease CKD-EPI) (Chronic eGFR Slope)

GroupValue (mL/min/1.73 m^2)Spread
Semaglutide-2.360.1
Placebo-3.300.1

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
SemaglutideParticipants received a dose of semaglutide subcutaneously once weekly with dose escalation in every 4 weeks in doses 0.25 mg (weeks 0-3), 0.50 mg (weeks 4-7) until the maintenance dose of 1 mg was reached at week 8 and continued 1 mg dose along with standard of care until end of the study (week 238). Participants were followed up for 5 weeks after end of treatment.227 / 1767877 / 1767507 / 1767
PlaceboParticipants received placebo matching semaglutide subcutaneously once weekly along with standard of care until end of the study (week 238). Participants were followed up for 5 weeks after end of treatment.279 / 1766950 / 1766522 / 1766

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies11

Studies that cite this trial.

Studies with results

8 studies on this page

Indexing hint: Clinical trial · 2026

REMODELing mechanistic trials for kidney disease: a multimodal, tissue-centered approach to understand the renal mechanism of action of semaglutide.

Pruijm et al. 2026Kidney internationalcited by 13

PMID 41207620DOI 10.1016/j.kint.2025.10.005PUB-41207620

Full text at the publisher
Publisher page

Indexing hint: Randomized controlled trial · 2026

9 results

Effect of semaglutide on COVID-19 and other infections: an analysis from the FLOW randomized clinical trial.

Rayner et al. 2026Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Associationcited by 3

PMID 41728915PMC13518088DOI 10.1093/ndt/gfag036PUB-41728915

CC BY9 results
Download PDFSee results (9)

Indexing hint: Randomized controlled trial · 2026

15 results

Kidney and Survival Benefits of Semaglutide in Diabetes With Chronic Kidney Disease: FLOW Trial Cardiovascular Subgroup Analyses.

Tuttle et al. 2026Journal of the American College of Cardiologycited by 1

PMID 42233552DOI 10.1016/j.jacc.2026.02.5125PUB-42233552

Full text at the publisher15 results
Publisher pageSee results (15)

Indexing hint: Meta-analysis (pooled) · 2025

15 results

Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes.

Natale et al. 2025The Cochrane database of systematic reviewscited by 8

PMID 39963952PMC11834151DOI 10.1002/14651858.cd015849.pub2PUB-39963952

Rights unknown15 results
Source linkSee results (15)

Indexing hint: Randomized controlled trial · 2025

7 results

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.

Rossing et al. 2025Cardiovascular diabetologycited by 2

PMID 41422027PMC12862915DOI 10.1186/s12933-025-03002-1PUB-41422027

Free to read · publisher termsCC BY-NC-ND7 results
Read at sourceSee results (7)

Indexing hint: Randomized controlled trial · 2024

7 results

Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes.

Perkovic et al. 2024The New England journal of medicinecited by 1,523

PMID 38785209DOI 10.1056/nejmoa2403347PUB-38785209

Full text at the publisher7 results
Publisher pageSee results (7)

Indexing hint: Randomized controlled trial · 2024

7 results

Effects of semaglutide with and without concomitant SGLT2 inhibitor use in participants with type 2 diabetes and chronic kidney disease in the FLOW trial.

Mann et al. 2024Nature medicinecited by 150

PMID 38914124PMC11485243DOI 10.1038/s41591-024-03133-0PUB-38914124

CC BY7 results
Download PDFSee results (7)

Indexing hint: Randomized controlled trial · 2024

5 results

Effects of Semaglutide on Heart Failure Outcomes in Diabetes and Chronic Kidney Disease in the FLOW Trial.

Pratley et al. 2024Journal of the American College of Cardiologycited by 90

PMID 39217553DOI 10.1016/j.jacc.2024.08.004PUB-39217553

Full text at the publisher5 results
Publisher pageSee results (5)

Indexing hint: Randomized controlled trial · 2024

4 results

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.

Kosiborod et al. 2024Lancet (London, England)cited by 232

PMID 39222642DOI 10.1016/s0140-6736(24)01643-xPUB-39222642

Full text at the publisher4 results
Publisher pageSee results (4)

More studies

2 studies on this page

PubMed tag: none · 2026

Kidney and Survival Outcomes with Semaglutide by CKD Severity in the FLOW Trial.

Tuttle et al. 2026Clinical journal of the American Society of Nephrology : CJASNcited by 4

PMID 41706532PMC13143484DOI 10.2215/cjn.0000000974PUB-41706532

CC BY
Download PDF

Indexing hint: Clinical trial · 2023

Corrected

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.

Rossing et al. 2023Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Associationcited by 175

PMID 36651820PMC10469096DOI 10.1093/ndt/gfad009PUB-36651820

Free to read · publisher termsCC BY-NC
Read at sourceRead the notice

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • DerivedMendonca 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. PMID 39480988
  • DerivedDe 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. PMID 38862303
  • DerivedCohen 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. PMID 35441935

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * Male or female, age above or equal to 18 years at the time of signing informed consent. Japan: Male or female, age above or equal to 20 years at the time of signing informed consent * Diagnosed with type 2 diabetes mellitus * HbA1c less than or equal to 10% (less than or equal to 86 mmol/mol) * Renal impairment defined either by: 1. serum creatinine-based eGFR greater than or equal to 50 and less than or equal to 75 mL/min/1.73 m\^2 (CKD-EPI) and UACR greater than 300 and less than 5000 mg/g or 2. serum creatinine-based eGFR greater than or equal to 25 and less than 50 mL/min/1.73 m\^2 (CKD-EPI) and UACR greater than 100 and less than 5000 mg/g * Treatment with maximum labelled or tolerated dose of a renin-angiotensin-aldosterone system (RAAS) blocking agent including an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB), unless such treatment is contraindicated or not tolerated. Treatment dose must be stable for at least 4 weeks prior to the date of the laboratory assessments used for determination of the inclusion criteria for renal impairment and kept stable until screening Exclusion Criteria: * Congenital or hereditary kidney diseases including polycystic kidney disease, autoimmune kidney diseases including glomerulonephritis or congenital urinary tract malformations * Use of any glucagon-like peptide-1 (GLP-1) receptor agonist within 30 days prior to screening * Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 60 days prior to the day of screening * Presently classified as being in New York Heart Association (NYHA) Class IV heart failure * Planned coronary, carotid or peripheral artery revascularisation * Current (or within 90 days) chronic or intermittent haemodialysis or peritoneal dialysis * Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination

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