← Trials/Trial dossier/NCT03819153

FLOW

CompletedPhase 3Results posted

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

Effect of Semaglutide Versus Placebo on the Progression of Renal Impairment in Subjects With Type 2 Diabetes and Chronic Kidney Disease

Lead sponsor

Novo Nordisk A/S

Asset

Semaglutide

GLP-1 agonist

Listed sites

413

Recruiting sites

—

Enrollment

3,533

actual

Study population

Chronic kidney disease, Type 2 diabetes

Key I/E criteria

•HbA1c ≤10%•eGFR ≥50•UACR ≥300

Primary endpoints

•Custom renal composite (eGFR, change, End-stage renal disease, Kidney-replacement therapy, Renal death)•5-point renal composite (eGFR, change, End-stage renal disease, Kidney-replacement therapy, Renal death)

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT03819153

Org study IDNN9535-4321

Secondary ID2018-002878-50European Medicines Agency (EudraCT)

Secondary IDJapicCTI-194843JAPIC (Japan)

Secondary IDU1111-1217-6259World Health Organization (WHO)

Timeline

Milestones

Study first posted2019-01-28actual

Study start2019-06-17actual

Primary completion2024-01-09actual

Study completion2024-01-09actual

Last update posted2025-03-20actual

Results first posted2025-03-20actual

Assets

Investigational agents

Semaglutide

Study populations

Who this study enrolls

Chronic kidney diseaseType 2 diabetes

Eligibility

Who can enroll

Minimum age18 Years

SexAll

Healthy volunteersNot accepted

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

Endpoints (44)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Renal / kidney

Cardiovascular outcomes

Cardiometabolic biomarkers

Weight & body composition

Glycemic / diabetes

Safety / tolerability / PK

Cardiovascular outcomes

14 endpoints

Secondary/registry result

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

Time frame:From Week 0 up to Week 234

Cardiovascular death

time to event, event

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide	123	—
Placebo	169	—

Secondary/registry result

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

3-point MACE

time to event, event

componentsCardiovascular death, Non-fatal MI, Non-fatal stroke

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide	212	—
Placebo	254	—

Secondary/registry result

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

Time frame:From Week 0 up to Week 234

All-cause death

time to event, event

SNOMED 419620001

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide	227	—
Placebo	279	—

Secondary/registry result

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

Non-fatal MI

event count, event

SNOMED 22298006

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide	52	—
Placebo	64	—

Secondary/registry result

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

Non-fatal stroke

time to event, event

SNOMED 230690007

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide	63	—
Placebo	51	—

Secondary/registry result

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

MALE composite (major adverse limb events)

composite event, event

componentsAcute limb ischemia, Peripheral-artery outcome composite

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide	16	—
Placebo	28	—

Secondary/registry result

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

Time frame:From Week 0 up to Week 234

Acute limb ischemia

event count, event

componentsAcute limb ischemia

Posted result

Group	Value (count_of_participants), Participants	95% CI
SemaglutideAcute limb ischaemia hospitalization	1	—
Chronic limb ischaemia hospitalization	16	—
PlaceboAcute limb ischaemia hospitalization	3	—
Chronic limb ischaemia hospitalization	25	—

Secondary/protocol endpoint

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

Time frame:From Week 0 up to Week 234

Cardiovascular death

time to event, event

Secondary/protocol endpoint

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

3-point MACE

time to event, event

componentsCardiovascular death, Non-fatal MI, Non-fatal stroke

Secondary/protocol endpoint

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

Time frame:From Week 0 up to Week 234

All-cause death

time to event, event

SNOMED 419620001

Secondary/protocol endpoint

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

Non-fatal MI

event count, event

SNOMED 22298006

Secondary/protocol endpoint

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

Non-fatal stroke

time to event, event

SNOMED 230690007

Secondary/protocol endpoint

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

Peripheral-artery outcome composite

composite event, event

componentsAcute limb ischemia

Secondary/protocol endpoint

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

Time frame:From Week 0 up to Week 234

MALE composite (major adverse limb events)

composite event, event

componentsAcute limb ischemia, Peripheral-artery outcome composite

Weight & body composition

2 endpoints

Secondary/registry result

Change From Baseline in Body Weight at Week 104

Time frame:Baeline (Week 0), Week 104

Body weight, absolute change (kg)

change from baseline, improvement

Posted result

Group	Value (mean), Kilograms	95% CI
Semaglutide	-5.54	—
Placebo	-1.43	—

Secondary/protocol endpoint

Change From Baseline in Body Weight at Week 104

Time frame:Baeline (Week 0), Week 104

Body weight, absolute change (kg)

change from baseline, improvement

Glycemic / diabetes

2 endpoints

Secondary/registry result

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

Time frame:Baseline (Week 0), Week 104

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

Group	Value (mean), Percentage of HbA1c	95% CI
Semaglutide	-0.86	—
Placebo	-0.04	—

Secondary/protocol endpoint

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

Time frame:Baseline (Week 0), Week 104

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Renal / kidney

20 endpoints

Primary/registry result

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

Custom renal composite

time to event, event

componentseGFR, change, End-stage renal disease, Kidney-replacement therapy, Renal death, Cardiovascular death

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide	331	—
Placebo	410	—

Hazard Ratio (HR)0.7695% CI0.66 – 0.88p0.0001Regression, Cox

Primary/protocol endpoint

Time frame:From Week 0 up to Week 234

5-point renal composite

time to event, event

componentseGFR, change, End-stage renal disease, Kidney-replacement therapy, Renal death, Cardiovascular death

Secondary/registry result

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

Time frame:From Week 0 up to Week 234

eGFR slope (total)

change from baseline, improvement

LOINC 98979-8

Posted result

Group	Value (mean), (mL/min/1.73 m^2)/year	95% CI
Semaglutide	-2.19	—
Placebo	-3.36	—

Secondary/registry result

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

eGFR, change

threshold achievement, event

LOINC 98979-8

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide	165	—
Placebo	213	—

Secondary/registry result

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

End-stage renal disease

threshold achievement, event

LOINC 98979-8 SNOMED 46177005

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide	92	—
Placebo	110	—

Secondary/registry result

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

Kidney-replacement therapy

time to event, event

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide	87	—
Placebo	100	—

Secondary/registry result

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

Time frame:From Week 0 up to Week 234

Renal death

time to event, event

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide	5	—
Placebo	5	—

Secondary/registry result

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

Time frame:Week 12, Week 234

eGFR slope (chronic)

change from baseline, improvement

LOINC 98979-8

Posted result

Group	Value (mean), mL/min/1.73 m^2	95% CI
Semaglutide	-2.36	—
Placebo	-3.30	—

Secondary/registry result

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

Time frame:Baseline (Week 0), Week 12

eGFR, change

change from baseline, improvement

LOINC 98979-8

Posted result

Group	Value (mean), mL/min/1.73m^2	95% CI
Semaglutide	-1.07	—
Placebo	-1.07	—

Secondary/registry result

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

Time frame:Baseline (Week 0), Week 104

eGFR, change

change from baseline, improvement

Posted result

Group	Value (mean), mL/min/1.73m^2	95% CI
Semaglutide	-2.1	—
Placebo	-5.4	—

Secondary/registry result

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

Time frame:Baseline (Week 0), Week 104

uACR, % change

ratio, improvement

LOINC 9318-7

Posted result

Group	Value (geometric_mean), Ratio	95% CI
Semaglutide	0.60	—
Placebo	0.89	—

Secondary/protocol endpoint

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

Time frame:From Week 0 up to Week 234

eGFR slope (total)

change from baseline, improvement

LOINC 98979-8

Secondary/protocol endpoint

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

Custom renal composite

time to event, event

LOINC 98979-8

Secondary/protocol endpoint

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

End-stage renal disease

time to event, event

SNOMED 46177005

Secondary/protocol endpoint

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

Kidney-replacement therapy

time to event, event

Secondary/protocol endpoint

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

Time frame:From Week 0 up to Week 234

Renal death

time to event, event

Secondary/protocol endpoint

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

Time frame:Week 12, Week 234

eGFR slope (chronic)

change from baseline, improvement

LOINC 98979-8

Secondary/protocol endpoint

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

Time frame:Baseline (Week 0), Week 12

eGFR, change

change from baseline, improvement

LOINC 98979-8

Secondary/protocol endpoint

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

Time frame:Baseline (Week 0), Week 104

eGFR, change

change from baseline, improvement

Secondary/protocol endpoint

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

Time frame:Baseline (Week 0), Week 104

uACR, change

ratio, improvement

LOINC 9318-7

Cardiometabolic biomarkers

4 endpoints

Secondary/registry result

Change From Baseline in Systolic Blood Pressure at Week 104

Time frame:Baseline (Week 0), Week 104

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Posted result

Group	Value (mean), Millimeters of mercury	95% CI
Semaglutide	-3.9	—
Placebo	-1.4	—

Secondary/registry result

Change From Baseline in Diastolic Blood Pressure at Week 104

Time frame:Baseline (Week 0), Week 104

Diastolic BP, change

change from baseline, improvement

LOINC 8462-4

Posted result

Group	Value (mean), millimeters of mercury	95% CI
Semaglutide	-0.4	—
Placebo	-0.8	—

Secondary/protocol endpoint

Change From Baseline in Systolic Blood Pressure at Week 104

Time frame:Baseline (Week 0), Week 104

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Secondary/protocol endpoint

Change From Baseline in Diastolic Blood Pressure at Week 104

Time frame:Baseline (Week 0), Week 104

Diastolic BP, change

change from baseline, improvement

LOINC 8462-4

Safety / tolerability / PK

2 endpoints

Secondary/registry result

Number of Severe Hypoglycaemic Episodes

Time frame:From Week 0 up to Week 234

Severe hypoglycemia

event count, event

Posted result

Group	Value (number), Episodes	95% CI
Semaglutide	37	—
Placebo	37	—

Secondary/protocol endpoint

Number of Severe Hypoglycaemic Episodes

Time frame:From Week 0 up to Week 234

Severe hypoglycemia

event count, event

Publications (15)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Effect of semaglutide on COVID-19 and other infections: an analysis from the FLOW randomized clinical trial.
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2026 Feb 23PMID41728915doi:10.1093/ndt/gfag036via clinicaltrials gov reference derived + pubmed nct search
Kidney and Survival Outcomes with Semaglutide by CKD Severity in the FLOW Trial.
Clinical journal of the American Society of Nephrology : CJASN2026 Feb 18PMID41706532doi:10.2215/CJN.0000000974via clinicaltrials gov reference derived + pubmed nct search
Prevalence and Associations of Systemic Inflammation in Heart Failure Across the Spectrum of Ejection Fraction.
JACC. Heart failure2026 Feb (month)PMID41099689doi:10.1016/j.jchf.2025.102712via pubmed nct search
REMODELing mechanistic trials for kidney disease: a multimodal, tissue-centered approach to understand the renal mechanism of action of semaglutide.
Kidney international2026 Jan (month)PMID41207620doi:10.1016/j.kint.2025.10.005via clinicaltrials gov reference derived + pubmed nct search
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.
Cardiovascular diabetology2025 Dec 20PMID41422027doi:10.1186/s12933-025-03002-1via clinicaltrials gov reference derived + pubmed nct search
Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes.
The Cochrane database of systematic reviews2025 Feb 18PMID39963952doi:10.1002/14651858.CD015849.pub2via clinicaltrials gov reference derived + pubmed nct search
The Impact of Glucagon-Like Peptide-1 Receptor Agonists on Kidney Outcomes: A Meta-Analysis of Randomized Placebo-Controlled Trials.
Clinical journal of the American Society of Nephrology : CJASN2025 Feb 1PMID39480988doi:10.2215/CJN.0000000584via clinicaltrials gov reference derived + pubmed nct search
Effects of Semaglutide on Heart Failure Outcomes in Diabetes and Chronic Kidney Disease in the FLOW Trial.
Journal of the American College of Cardiology2024 Oct 22PMID39217553doi:10.1016/j.jacc.2024.08.004via clinicaltrials gov reference derived + pubmed nct search
Effects of semaglutide with and without concomitant SGLT2 inhibitor use in participants with type 2 diabetes and chronic kidney disease in the FLOW trial.
Nature medicine2024 Oct (month)PMID38914124doi:10.1038/s41591-024-03133-0via clinicaltrials gov reference derived + pubmed nct search
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 (London, England)2024 Sep 7PMID39222642doi:10.1016/S0140-6736(24)01643-Xvia clinicaltrials gov reference derived + pubmed nct search
Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes.
The New England journal of medicine2024 Jul 11PMID38785209doi:10.1056/NEJMoa2403347via clinicaltrials gov reference derived + pubmed nct search
Response to "Experience with dulaglutide in an obese diabetic patient on incremental peritoneal dialysis". Response to related letter.
Nefrologia2024 May-Jun (year)PMID38862303doi:10.1016/j.nefroe.2023.10.010via clinicaltrials gov reference derived + pubmed nct search
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.
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2023 Aug 31PMID36651820doi:10.1093/ndt/gfad009via CT.gov background + pubmed nct search
Glucagon-like peptide-1 receptor agonists in diabetic kidney disease: A review of their kidney and heart protection.
American journal of preventive cardiology2023 Jun (month)PMID37313358doi:10.1016/j.ajpc.2023.100502via pubmed nct search
Mineralocorticoid Receptor Antagonists in the Treatment of Diabetic Kidney Disease: Their Application in the Era of SGLT2 Inhibitors and GLP-1 Receptor Agonists.
Current diabetes reports2022 May (month)PMID35441935doi:10.1007/s11892-022-01461-4via clinicaltrials gov reference derived + pubmed nct search

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.