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 JFE, Rossing P, Bakris G, Belmar N, Bosch-Traberg H, Busch R, Charytan DM, Hadjadj S, Gillard P, Górriz JL, Idorn T, Ji L and 6 more

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Mahaffey KW, Perkovic V, Rasmussen S, Schmieder RE, Pratley RE, Tuttle KR

Nature medicine24 Jun 2024Cited by 150 (Europe PMC)

PMID38914124PMCIDPMC11485243DOI10.1038/s41591-024-03133-0PepBankPUB-38914124

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Summary

People with type 2 diabetes and chronic kidney disease have a high risk for kidney failure and cardiovascular (CV) complications. Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors (SGLT2i) independently reduce CV and kidney events. The effect of combining both is unclear. FLOW trial participants with type 2 diabetes and chronic kidney disease were stratified by baseline SGLT2i use (N = 550) or no use (N = 2,983) and randomized to semaglutide/placebo. The primary outcome was a composite of kidney failure, ≥50% estimated glomerular filtration rate reduction, kidney death or CV death. The risk of the primary outcome was 24% lower in all participants treated with semaglutide versus placebo (95% confidence interval: 34%, 12%). The primary outcome occurred in 41/277 (semaglutide) versus 38/273 (placebo) participants on SGLT2i at baseline (hazard ratio 1.07; 95% confidence interval: 0.69, 1.67; P = 0.755) and in 290/1,490 versus 372/1,493 participants not taking SGLT2i at baseline (hazard ratio 0.73; 0.63, 0.85; P < 0.001; P interaction 0.109). Three confirmatory secondary outcomes were predefined. Treatment differences favoring semaglutide for total estimated glomerular filtration rate slope (ml min^-1/1.73 m²/year) were 0.75 (-0.01, 1.5) in the SGLT2i subgroup and 1.25 (0.91, 1.58) in the non-SGLT2i subgroup, P interaction 0.237. Semaglutide benefits on major CV events and all-cause death were similar regardless of SGLT2i use (P interaction 0.741 and 0.901, respectively). The benefits of semaglutide in reducing kidney outcomes were consistent in participants with/without baseline SGLT2i use; power was limited to detect smaller but clinically relevant effects. ClinicalTrials.gov identifier: NCT03819153 .

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

7 results from studies that gave the peptide. 7 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes and chronic kidney disease not taking an SGLT2 inhibitor at baseline, semaglutide lowered the primary composite outcome versus placebo.
In plain wordsIn adults with type 2 diabetes and kidney disease not taking an SGLT2 inhibitor, semaglutide lowered the risk of the primary outcome compared with placebo.
Peptide
Semaglutide
Outcome
DecreasePrimary composite in participants not on SGLT2 inhibitor
Study
n = 2,983
Comparator
Placebo
Analysis
Primary
Outcome group
Kidney function · Kidney and urinary
Studied dose
Dose not stated
Measurements
Hazard ratio
0.73 ratio
no SGLT2i at baseline
Source sentences
Summary
and in 290/1,490 versus 372/1,493 participants not taking SGLT2i at baseline (hazard ratio 0.73; 0.63, 0.85; P < 0.001
1 context sentence(design, population, supporting numbers)
Summary · context
FLOW trial participants with type 2 diabetes and chronic kidney disease were stratified by baseline SGLT2i use (N = 550) or no use (N = 2,983) and randomized to semaglutide/placebo.
Show in the study text Report a problemFND-3891412403
02HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes and chronic kidney disease who took an SGLT2 inhibitor at baseline, semaglutide did not significantly change the primary composite outcome versus placebo.
In plain wordsIn adults with type 2 diabetes and kidney disease already taking an SGLT2 inhibitor, semaglutide did not clearly change the primary outcome compared with placebo.
Peptide
Semaglutide
Outcome
No significant changePrimary composite in participants on SGLT2 inhibitor
Study
n = 550
Comparator
Placebo
Analysis
Primary
Outcome group
Kidney function · Kidney and urinary
Studied dose
Dose not stated
Measurements
Hazard ratio
1.07 ratio
SGLT2i at baseline
Source sentences
Summary
The primary outcome occurred in 41/277 (semaglutide) versus 38/273 (placebo) participants on SGLT2i at baseline (hazard ratio 1.07; 95% confidence interval: 0.69, 1.67; P = 0.755)
1 context sentence(design, population, supporting numbers)
Summary · context
FLOW trial participants with type 2 diabetes and chronic kidney disease were stratified by baseline SGLT2i use (N = 550) or no use (N = 2,983) and randomized to semaglutide/placebo.
Show in the study text Report a problemFND-3891412402
03HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes and chronic kidney disease, semaglutide lowered the risk of the primary composite outcome by 24% versus placebo.
In plain wordsIn adults with type 2 diabetes and kidney disease, semaglutide lowered the risk of kidney failure, kidney decline or heart death by 24% versus placebo.
Peptide
Semaglutide
Outcome
DecreasePrimary kidney and CV composite, all participants
Study
n: not reported in source
Comparator
Placebo
Analysis
Primary
Outcome group
Kidney function · Kidney and urinary
Studied dose
Dose not stated
Measurements
Risk reduction of primary outcome
24%
all participants
Source sentences
Summary
The risk of the primary outcome was 24% lower in all participants treated with semaglutide versus placebo (95% confidence interval: 34%, 12%).
1 context sentence(design, population, supporting numbers)
Summary · context
FLOW trial participants with type 2 diabetes and chronic kidney disease were stratified by baseline SGLT2i use (N = 550) or no use (N = 2,983) and randomized to semaglutide/placebo.
Show in the study text Report a problemFND-3891412401
04HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes and chronic kidney disease not on an SGLT2 inhibitor, semaglutide slowed the eGFR decline versus placebo.
In plain wordsIn adults with type 2 diabetes and kidney disease not on an SGLT2 inhibitor, semaglutide slowed the yearly decline in kidney function compared with placebo.
Peptide
Semaglutide
Outcome
IncreaseeGFR slope in participants not on SGLT2 inhibitor
Study
n = 2,983
Comparator
Placebo
Analysis
Secondary
Outcome group
Kidney function · Kidney and urinary
Studied dose
Dose not stated
Measurements
eGFR slope treatment difference
1.25 ml/min/1.73 m2/year
non-SGLT2i subgroup
Source sentences
Summary
and 1.25 (0.91, 1.58) in the non-SGLT2i subgroup
1 context sentence(design, population, supporting numbers)
Summary · context
FLOW trial participants with type 2 diabetes and chronic kidney disease were stratified by baseline SGLT2i use (N = 550) or no use (N = 2,983) and randomized to semaglutide/placebo.
Show in the study text Report a problemFND-3891412405
05HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes and chronic kidney disease on an SGLT2 inhibitor, the eGFR slope difference with semaglutide versus placebo had a confidence interval that included zero.
In plain wordsIn adults with type 2 diabetes and kidney disease on an SGLT2 inhibitor, semaglutide did not clearly change yearly kidney function decline versus placebo.
Peptide
Semaglutide
Outcome
No significant changeeGFR slope in participants on SGLT2 inhibitor
Study
n = 550
Comparator
Placebo
Analysis
Secondary
Outcome group
Kidney function · Kidney and urinary
Studied dose
Dose not stated
Measurements
eGFR slope treatment difference
0.75 ml/min/1.73 m2/year
SGLT2i subgroup
Source sentences
Summary
were 0.75 (-0.01, 1.5) in the SGLT2i subgroup
1 context sentence(design, population, supporting numbers)
Summary · context
FLOW trial participants with type 2 diabetes and chronic kidney disease were stratified by baseline SGLT2i use (N = 550) or no use (N = 2,983) and randomized to semaglutide/placebo.
Show in the study text Report a problemFND-3891412404
06HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes and chronic kidney disease, the semaglutide benefit on major CV events did not differ by SGLT2 inhibitor use.
In plain wordsIn adults with type 2 diabetes and kidney disease, the heart benefit of semaglutide over placebo was similar with or without an SGLT2 inhibitor.
Peptide
Semaglutide
Outcome
DecreaseMajor CV events by SGLT2 inhibitor use
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Semaglutide benefits on major CV events and all-cause death were similar regardless of SGLT2i use (P interaction 0.741 and 0.901, respectively).
1 context sentence(design, population, supporting numbers)
Summary · context
FLOW trial participants with type 2 diabetes and chronic kidney disease were stratified by baseline SGLT2i use (N = 550) or no use (N = 2,983) and randomized to semaglutide/placebo.
Show in the study text Report a problemFND-3891412406
07HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes and chronic kidney disease, the semaglutide benefit on all-cause death did not differ by SGLT2 inhibitor use.
In plain wordsIn adults with type 2 diabetes and kidney disease, semaglutide effect on death from any cause was similar with or without an SGLT2 inhibitor.
Peptide
Semaglutide
Outcome
DecreaseAll-cause death by SGLT2 inhibitor use
Study
n: not reported in source
Comparator
Placebo
Analysis
Secondary
Outcome group
Mortality · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Semaglutide benefits on major CV events and all-cause death were similar regardless of SGLT2i use (P interaction 0.741 and 0.901, respectively).
1 context sentence(design, population, supporting numbers)
Summary · context
FLOW trial participants with type 2 diabetes and chronic kidney disease were stratified by baseline SGLT2i use (N = 550) or no use (N = 2,983) and randomized to semaglutide/placebo.
Show in the study text Report a problemFND-3891412407

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3Results postedNCT03819153

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

Novo Nordisk A/Sn = 3,53317 Jun 2019 to 9 Jan 2024

Diabetes Mellitus, Type 2

Trial page ClinicalTrials.govUpdated 20 Mar 2025

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
11 Oct 2026, 00:04 UTC
Study results updated
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

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