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CompletedPhase 2Results posted

A Research Study Looking at How Well a Combination of the Medicines Semaglutide and NNC0480-0389 Works in People With Type 2 Diabetes

Investigation of the Safety and Efficacy of Semaglutide s.c. in Combination With NNC0480-0389 in Participants With Type 2 Diabetes - a Dose Finding Study

Lead sponsor

Novo Nordisk A/S

Assets

NNC0480-0389 / Semaglutide

Listed sites

129

Recruiting sites

Enrollment

500

actual

Study population

Obesity / overweight, Type 2 diabetes

Key I/E criteria

BMI ≥25HbA1c 7-10%

Primary endpoint

HbA1c, change

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 IDNCT05144984
Org study IDNN9389-4606
Secondary ID2020-004863-14
Secondary IDjRCT2031210474Japanese Registration Number
Secondary IDU1111-1259-2741World Health Organization (WHO)

Timeline

Milestones

Study start2021-11-29actual
Study first posted2021-12-06actual
Primary completion2023-02-13actual
Study completion2023-03-23actual
Last update posted2026-04-09actual
Results first posted2026-04-09actual

Assets

Investigational agents

Study populations

Who this study enrolls

Obesity / overweightType 2 diabetes

Eligibility

Who can enroll

Minimum age18 Years
Maximum age75 Years
SexAll
Healthy volunteersNot accepted

Inclusion criteria

Diagnosed with type 2 diabetes mellitus greater than or equal to 180 days before screening
Participants treated with diet and exercise as monotherapy or in combination with stable daily dose(s) greater than or equal to 90 days before screening of any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose
HbA1c 7.0-10.0% (53-86 mmol/mol) (both inclusive)
BMI greater than or equal to 25 and below 40 kg/m^2

Exclusion criteria

Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening. However, short term insulin treatment for a maximum of 14 days and prior insulin treatment for gestational diabetes are allowed
Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within 90 days before 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
Presence or history of any clinically relevant respiratory, metabolic, renal, hepatic cardiovascular, gastrointestinal, or endocrinological conditions (except conditions associated with T2D)

Endpoints (30)

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

Cardiometabolic biomarkers
18
Weight & body composition
6
Glycemic / diabetes
4
Safety / tolerability / PK
2

Weight & body composition

6 endpoints
Secondary/registry result

Change From Baseline in Body Weight (Kilogram [kg])

Time frame:Baseline (week 0), (week 34)

Body weight, absolute change (kg)

change from baseline, improvement

Posted result

GroupValue (mean), Kilogram (kg)95% CI
Semaglutide 2.4 mg + NNC0480-0389 2.4 mg-8.9
Semaglutide 2.4 mg + NNC0480-0389 7.2 mg-12
Semaglutide 2.4 mg + NNC0480-0389 12.0 mg-10
Semaglutide 2.4 mg + NNC0480-0389 21.6 mg-12
Semaglutide 2.4 mg + Placebo (NNC0480-0389)-9.8
NNC0480-0389 21.6 mg + Placebo (Semaglutide)-4.7
Placebo-2.6
Secondary/registry result

Percent Change From Baseline in Body Weight

Time frame:Baseline (week 0), (week 34)

Body weight, % change

percent change from baseline, improvement

Posted result

GroupValue (mean), Percent Change of body weight95% CI
Semaglutide 2.4 mg + NNC0480-0389 2.4 mg-9.3
Semaglutide 2.4 mg + NNC0480-0389 7.2 mg-13
Semaglutide 2.4 mg + NNC0480-0389 12.0 mg-11
Semaglutide 2.4 mg + NNC0480-0389 21.6 mg-13
Semaglutide 2.4 mg + Placebo (NNC0480-0389)-10
NNC0480-0389 21.6 mg + Placebo (Semaglutide)-4.3
Placebo-2.7
Secondary/registry result

Change From Baseline in Waist Circumference

Time frame:Baseline (week 0), (week 34)

Waist circumference, change

change from baseline, improvement

Posted result

GroupValue (mean), Centimeter (cm)95% CI
Semaglutide 2.4 mg + NNC0480-0389 2.4 mg-8
Semaglutide 2.4 mg + NNC0480-0389 7.2 mg-11
Semaglutide 2.4 mg + NNC0480-0389 12.0 mg-9
Semaglutide 2.4 mg + NNC0480-0389 21.6 mg-10
Semaglutide 2.4 mg + Placebo (NNC0480-0389)-8
NNC0480-0389 21.6 mg + Placebo (Semaglutide)-5
Placebo-3
Secondary/protocol endpoint

Change From Baseline in Body Weight (Kilogram [kg])

Time frame:Baseline (week 0), (week 34)

Body weight, absolute change (kg)

change from baseline, improvement

Secondary/protocol endpoint

Percent Change From Baseline in Body Weight

Time frame:Baseline (week 0), (week 34)

Body weight, % change

percent change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Waist Circumference

Time frame:Baseline (week 0), (week 34)

Waist circumference, change

change from baseline, improvement

Glycemic / diabetes

4 endpoints
Primary/registry result

Change From Baseline in Glycosylated Haemoglobin (HbA1c)

Time frame:Baseline (week 0), (week 34)

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

GroupValue (mean), Percentage point of HbA1c95% CI
Semaglutide 2.4 mg + NNC0480-0389 2.4 mg-2.3
Semaglutide 2.4 mg + NNC0480-0389 7.2 mg-2.2
Semaglutide 2.4 mg + NNC0480-0389 12.0 mg-2.2
Semaglutide 2.4 mg + NNC0480-0389 21.6 mg-2.3
Semaglutide 2.4 mg + Placebo (NNC0480-0389)-2.3
NNC0480-0389 21.6 mg + Placebo (Semaglutide)-1.1
Placebo-0.4
Estimated treatment difference-1.995% CI-2.3-1.4p<0.0001ANCOVA

Hypothetical estimand

Estimated treatment difference-2.095% CI-2.5-1.5p<0.0001ANCOVA

Hypothetical estimand

Estimated treatment difference-1.995% CI-2.4-1.5p<0.0001ANCOVA

Hypothetical estimand

Estimated treatment difference-1.995% CI-2.4-1.5p<0.0001ANCOVA

Hypothetical estimand

Primary/protocol endpoint

Change From Baseline in Glycosylated Haemoglobin (HbA1c)

Time frame:Baseline (week 0), (week 34)

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/registry result

Change From Baseline in Fasting Plasma Glucose (FPG)

Time frame:Baseline (week 0), (week 34)

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

GroupValue (mean), millimoles per litre (mmol/L)95% CI
Semaglutide 2.4 mg + NNC0480-0389 2.4 mg-3.9
Semaglutide 2.4 mg + NNC0480-0389 7.2 mg-3.4
Semaglutide 2.4 mg + NNC0480-0389 12.0 mg-3.8
Semaglutide 2.4 mg + NNC0480-0389 21.6 mg-3.8
Semaglutide 2.4 mg + Placebo (NNC0480-0389)-3.6
NNC0480-0389 21.6 mg + Placebo (Semaglutide)-1.4
Placebo-0.1
Secondary/protocol endpoint

Change From Baseline in Fasting Plasma Glucose (FPG)

Time frame:Baseline (week 0), (week 34)

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Cardiometabolic biomarkers

18 endpoints
Secondary/registry result

Change From Baseline in Systolic Blood Pressure (SBP)

Time frame:Baseline (week 0), (week 34)

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Posted result

GroupValue (mean), Millimeters of mercury (mmHg)95% CI
Semaglutide 2.4 mg + NNC0480-0389 2.4 mg-6
Semaglutide 2.4 mg + NNC0480-0389 7.2 mg-10
Semaglutide 2.4 mg + NNC0480-0389 12.0 mg-9
Semaglutide 2.4 mg + NNC0480-0389 21.6 mg-13
Semaglutide 2.4 mg + Placebo (NNC0480-0389)-5
NNC0480-0389 21.6 mg + Placebo (Semaglutide)-3
Placebo0
Secondary/registry result

Relative Change From Baseline in Total Cholesterol - Ratio to Baseline

Time frame:Baseline (week 0), (week 34)

Total cholesterol, change

ratio, improvement

LOINC 2093-3

Posted result

GroupValue (geometric_mean), Ratio of total cholesterol95% CI
Semaglutide 2.4 mg + NNC0480-0389 2.4 mg0.94
Semaglutide 2.4 mg + NNC0480-0389 7.2 mg0.89
Semaglutide 2.4 mg + NNC0480-0389 12.0 mg0.90
Semaglutide 2.4 mg + NNC0480-0389 21.6 mg0.90
Semaglutide 2.4 mg + Placebo (NNC0480-0389)0.93
NNC0480-0389 21.6 mg + Placebo (Semaglutide)1.00
Placebo0.96
Secondary/registry result

Relative Change From Baseline in High-Density Lipoprotein (HDL) Cholesterol - Ratio to Baseline

Time frame:Baseline (week 0), (week 34)

HDL-C, change

ratio, improvement

LOINC 2085-9

Posted result

GroupValue (geometric_mean), Ratio of HDL cholesterol95% CI
Semaglutide 2.4 mg + NNC0480-0389 2.4 mg1.05
Semaglutide 2.4 mg + NNC0480-0389 7.2 mg1.06
Semaglutide 2.4 mg + NNC0480-0389 12.0 mg1.07
Semaglutide 2.4 mg + NNC0480-0389 21.6 mg1.00
Semaglutide 2.4 mg + Placebo (NNC0480-0389)1.04
NNC0480-0389 21.6 mg + Placebo (Semaglutide)1.04
Placebo1.04
Secondary/registry result

Relative Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol - Ratio to Baseline

Time frame:Baseline (week 0), (week 34)

LDL-C, change

ratio, improvement

LOINC 13457-7

Posted result

GroupValue (geometric_mean), Ratio of LDL cholesterol95% CI
Semaglutide 2.4 mg + NNC0480-0389 2.4 mg0.95
Semaglutide 2.4 mg + NNC0480-0389 7.2 mg0.85
Semaglutide 2.4 mg + NNC0480-0389 12.0 mg0.91
Semaglutide 2.4 mg + NNC0480-0389 21.6 mg0.88
Semaglutide 2.4 mg + Placebo (NNC0480-0389)0.95
NNC0480-0389 21.6 mg + Placebo (Semaglutide)0.96
Placebo0.96
Secondary/registry result

Relative Change From Baseline in Very-Low Density Lipoprotein (VLDL) Cholesterol - Ratio to Baseline

Time frame:Baseline (week 0), (week 34)

VLDL, change

ratio, improvement

Posted result

GroupValue (geometric_mean), Ratio of VLDL cholesterol95% CI
Semaglutide 2.4 mg + NNC0480-0389 2.4 mg0.75
Semaglutide 2.4 mg + NNC0480-0389 7.2 mg0.76
Semaglutide 2.4 mg + NNC0480-0389 12.0 mg0.72
Semaglutide 2.4 mg + NNC0480-0389 21.6 mg0.78
Semaglutide 2.4 mg + Placebo (NNC0480-0389)0.72
NNC0480-0389 21.6 mg + Placebo (Semaglutide)0.95
Placebo0.86
Secondary/registry result

Relative Change From Baseline in Triglycerides - Ratio to Baseline

Time frame:Baseline (week 0), (week 34)

Triglycerides, change

ratio, improvement

LOINC 2571-8

Posted result

GroupValue (geometric_mean), Ratio of triglycerides95% CI
Semaglutide 2.4 mg + NNC0480-0389 2.4 mg0.75
Semaglutide 2.4 mg + NNC0480-0389 7.2 mg0.76
Semaglutide 2.4 mg + NNC0480-0389 12.0 mg0.72
Semaglutide 2.4 mg + NNC0480-0389 21.6 mg0.78
Semaglutide 2.4 mg + Placebo (NNC0480-0389)0.72
NNC0480-0389 21.6 mg + Placebo (Semaglutide)0.96
Placebo0.86
Secondary/registry result

Relative Change From Baseline in Free Fatty Acids - Ratio to Baseline

Time frame:Baseline (week 0), (week 34)

Free fatty acids, change

ratio, improvement

Posted result

GroupValue (geometric_mean), Ratio of free fatty acids95% CI
Semaglutide 2.4 mg + NNC0480-0389 2.4 mg0.85
Semaglutide 2.4 mg + NNC0480-0389 7.2 mg0.74
Semaglutide 2.4 mg + NNC0480-0389 12.0 mg0.77
Semaglutide 2.4 mg + NNC0480-0389 21.6 mg0.75
Semaglutide 2.4 mg + Placebo (NNC0480-0389)0.88
NNC0480-0389 21.6 mg + Placebo (Semaglutide)0.96
Placebo0.91
Secondary/registry result

Relative Change From Baseline in Apolipoprotein B (ApoB) - Ratio to Baseline

Time frame:Baseline (week 0), (week 34)

ApoB, change

ratio, improvement

Posted result

GroupValue (geometric_mean), Ratio of ApoB95% CI
Semaglutide 2.4 mg + NNC0480-0389 2.4 mg0.90
Semaglutide 2.4 mg + NNC0480-0389 7.2 mg0.84
Semaglutide 2.4 mg + NNC0480-0389 12.0 mg0.85
Semaglutide 2.4 mg + NNC0480-0389 21.6 mg0.85
Semaglutide 2.4 mg + Placebo (NNC0480-0389)0.91
NNC0480-0389 21.6 mg + Placebo (Semaglutide)1.00
Placebo0.94
Secondary/registry result

Relative Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) - Ratio to Baseline

Time frame:Baseline (week 0), (week 34)

hs-CRP, change

ratio, improvement

LOINC 30522-7

Posted result

GroupValue (geometric_mean), Ratio of hsCRP95% CI
Semaglutide 2.4 mg + NNC0480-0389 2.4 mg0.56
Semaglutide 2.4 mg + NNC0480-0389 7.2 mg0.54
Semaglutide 2.4 mg + NNC0480-0389 12.0 mg0.64
Semaglutide 2.4 mg + NNC0480-0389 21.6 mg0.66
Semaglutide 2.4 mg + Placebo (NNC0480-0389)0.61
NNC0480-0389 21.6 mg + Placebo (Semaglutide)0.82
Placebo0.93
Secondary/protocol endpoint

Change From Baseline in Systolic Blood Pressure (SBP)

Time frame:Baseline (week 0), (week 34)

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Secondary/protocol endpoint

Relative Change From Baseline in Total Cholesterol - Ratio to Baseline

Time frame:Baseline (week 0), (week 34)

Total cholesterol, change

ratio, improvement

LOINC 2093-3

Secondary/protocol endpoint

Relative Change From Baseline in High-Density Lipoprotein (HDL) Cholesterol - Ratio to Baseline

Time frame:Baseline (week 0), (week 34)

HDL-C, change

ratio, improvement

LOINC 2085-9

Secondary/protocol endpoint

Relative Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol - Ratio to Baseline

Time frame:Baseline (week 0), (week 34)

LDL-C, change

ratio, improvement

LOINC 13457-7

Secondary/protocol endpoint

Relative Change From Baseline in Very-Low Density Lipoprotein (VLDL) Cholesterol - Ratio to Baseline

Time frame:Baseline (week 0), (week 34)

VLDL, change

ratio, improvement

Secondary/protocol endpoint

Relative Change From Baseline in Triglycerides - Ratio to Baseline

Time frame:Baseline (week 0), (week 34)

Triglycerides, change

ratio, improvement

LOINC 2571-8

Secondary/protocol endpoint

Relative Change From Baseline in Free Fatty Acids - Ratio to Baseline

Time frame:Baseline (week 0), (week 34)

Free fatty acids, change

ratio, improvement

Secondary/protocol endpoint

Relative Change From Baseline in Apolipoprotein B (ApoB) - Ratio to Baseline

Time frame:Baseline (week 0), (week 34)

ApoB, change

ratio, improvement

Secondary/protocol endpoint

Relative Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) - Ratio to Baseline

Time frame:Baseline (week 0), (week 34)

hs-CRP, change

ratio, improvement

LOINC 30522-7

Safety / tolerability / PK

2 endpoints
Secondary/registry result

Number of Treatment-Emergent Adverse Events (TEAEs)

Time frame:Baseline (week 0) to (week 39)

Treatment-emergent AEs (any)

event count, event

Posted result

GroupValue (number), Events95% CI
Semaglutide 2.4 mg + NNC0480-0389 2.4 mg229
Semaglutide 2.4 mg + NNC0480-0389 7.2 mg304
Semaglutide 2.4 mg + NNC0480-0389 12.0 mg206
Semaglutide 2.4 mg + NNC0480-0389 21.6 mg308
Semaglutide 2.4 mg + Placebo (NNC0480-0389)271
NNC0480-0389 21.6 mg + Placebo (Semaglutide)240
Placebo95
Secondary/protocol endpoint

Number of Treatment-Emergent Adverse Events (TEAEs)

Time frame:Baseline (week 0) to (week 39)

Treatment-emergent AEs (any)

event count, event

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.