← Trials/Trial dossier/NCT02827708

PIONEER 5

CompletedPhase 3Results posted

Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes and Moderate Renal Impairment

Lead sponsor

Novo Nordisk A/S

Asset

Semaglutide

Oral · GLP-1 agonist

Listed sites

117

Recruiting sites

—

Enrollment

324

actual

Study population

Renal impairment, Type 2 diabetes

Key I/E criteria

•HbA1c 7-9.5%•eGFR 30-59

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 IDNCT02827708

Org study IDNN9924-4234

Secondary ID2015-005326-19

Secondary IDU1111-1176-9230WHO

Timeline

Milestones

Study first posted2016-07-11estimated

Study start2016-09-20actual

Primary completion2018-04-10actual

Study completion2018-05-15actual

Last update posted2020-02-17actual

Results first posted2020-02-17actual

Assets

Investigational agents

Semaglutide

Study populations

Who this study enrolls

Renal impairmentType 2 diabetes

Eligibility

Who can enroll

Minimum age18 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial

•Male or female, age above or equal to 18 years at the time of signing informed consent

•Diagnosed with type 2 diabetes mellitus for at least 90 days prior to day of screening

•HbA1c (glycosylated haemoglobin) of 7.0-9.5% (53-80 mmol/mol) (both inclusive)

•Moderate renal impairment defined as estimated glomerular filtration rate of 30-59 mL/min/1.73 m^2 as per Chronic Kidney Disease Epidemiology Collaboration formula

•Stable daily dose(s) within 90 days prior to the day of screening of any of the following treatment regimens:

•1-2 of the following oral anti-diabetic drugs:

•Metformin equal or above 1500 mg or maximum tolerated dose documented in the subject medical record),

•Sulfonylurea (equal or above half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record)

•Basal insulin alone (20% change in total daily dose of insulin glargine, insulin detemir, insulin degludec or NPH insulin) or

•Metformin (equal or above 1500 mg or maximum tolerated dose documented in the subject medical record) in combination with basal insulin (20% change in total daily dose of insulin glargine, insulin detemir, insulin degludec or NPH insulin)

Exclusion criteria

•Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measure as required by local regulation or practice). For certain specific countries: Additional specific requirements apply

•Any disorder, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol

•Family or personal history of Multiple Endocrine Neoplasia Type 2 or Medullary Thyroid Carcinoma

•History of pancreatitis (acute or chronic)

•History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery)

•Any of the following: myocardial infarction, stroke or hospitalisation for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening and randomisation

•Subjects presently classified as being in New York Heart Association Class IV

•Planned coronary, carotid or peripheral artery revascularisation known on the day of screening

•Subjects with alanine aminotransferase above 2.5 x upper normal limit

•Rapidly progressing renal disease (e.g. such as acute glomerulonephritis) as judged by the investigator or known nephrotic albuminuria (above 2200 mg/24 hours or above 2200 mg/g)

•Use of systemic immunosuppressive treatment within 90 days prior to screening

•Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before the day of screening. An exception is short-term insulin treatment for acute illness for a total of below or equal to 14 days

•Known hypoglycaemic unawareness and/or recurrent severe hypoglycaemic episodes as judged by the investigator

•Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or dilated fundoscopy performed within 90 days prior to randomisation

•History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and carcinoma in situ)

Endpoints (80)

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

Safety / tolerability / PK

Glycemic / diabetes

Cardiometabolic biomarkers

Weight & body composition

Patient-reported / QoL

Renal / kidney

Other clinical outcomes

Weight & body composition

12 endpoints

Secondary/registry result

Change in Body Weight (kg)

Time frame:Week 0, week 26

Body weight, absolute change (kg)

change from baseline, improvement

Posted result

Group	Value (mean), kg	95% CI
Oral Semaglutide 14 mgIn-trial	-3.5	—
On-treatment without rescue medication	-3.9	—
PlaceboIn-trial	-0.9	—
On-treatment without rescue medication	-0.9	—

Treatment difference-2.595% CI-3.2 – -1.8p<0.0001Pattern Mixture model

Treatment difference-2.795% CI-3.5 – -1.9p<0.0001MMRM

Secondary/registry result

Change in Body Weight (%)

Time frame:Week 0, week 26

Body weight, % change

percent change from baseline, improvement

Posted result

Group	Value (mean), Percentage change	95% CI
Oral Semaglutide 14 mg	-3.75	—
Placebo	-0.92	—

Secondary/registry result

Change in BMI

Time frame:Week 0, week 26

BMI, change

change from baseline, improvement

Posted result

Group	Value (mean), kg/m^2	95% CI
Oral Semaglutide 14 mg	-1.2	—
Placebo	-0.3	—

Secondary/registry result

Change in Waist Circumference

Time frame:Week 0, week 26

Waist circumference, change

change from baseline, improvement

Posted result

Group	Value (mean), Centimetre (cm)	95% CI
Oral Semaglutide 14 mg	-2.8	—
Placebo	-0.7	—

Secondary/registry result

Participants Who Achieve Weight Loss ≥5% (Yes/no)

Time frame:Week 26

≥5% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mgYes	55	—
No	99	—
PlaceboYes	15	—
No	140	—

Secondary/registry result

Participants Who Achieve Weight Loss ≥10% (Yes/no)

Time frame:Week 26

≥10% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mgYes	13	—
No	141	—
PlaceboYes	0	—
No	155	—

Secondary/protocol endpoint

Change in Body Weight (kg)

Time frame:Week 0, week 26

Body weight, absolute change (kg)

change from baseline, improvement

Secondary/protocol endpoint

Change in Body Weight (%)

Time frame:Week 0, week 26

Body weight, % change

percent change from baseline, improvement

Secondary/protocol endpoint

Change in BMI

Time frame:Week 0, week 26

BMI, change

change from baseline, improvement

Secondary/protocol endpoint

Change in Waist Circumference

Time frame:Week 0, week 26

Waist circumference, change

change from baseline, improvement

Secondary/protocol endpoint

Participants Who Achieve Weight Loss ≥5% (Yes/no)

Time frame:Week 26

≥5% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

Participants Who Achieve Weight Loss ≥10% (Yes/no)

Time frame:Week 26

≥10% weight-loss responders

threshold achievement, improvement

Glycemic / diabetes

16 endpoints

Primary/registry result

Change in HbA1c

Time frame:Week 0, week 26

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

Group	Value (mean), Percentage of HbA1c	95% CI
Oral Semaglutide 14 mgIn-trial	-1.1	—
On-treatment without rescue medication	-1.2	—
PlaceboIn-trial	-0.2	—
On-treatment without rescue medication	-0.1	—

Treatment difference-0.895% CI-1.0 – -0.6p<0.0001Pattern Mixture model

Treatment difference-1.095% CI-1.2 – -0.8p<0.0001MMRM

Primary/protocol endpoint

Change in HbA1c

Time frame:Week 0, week 26

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/registry result

Change in FPG

Time frame:Week 0, week 26

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

Group	Value (mean), mmol/L	95% CI
Oral Semaglutide 14 mg	-1.58	—
Placebo	-0.34	—

Secondary/registry result

Participants Who Achieve HbA1c <7.0% (53 mmol/Mol), ADA Target (Yes/no)

Time frame:Week 26

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mgYes	89	—
No	65	—
PlaceboYes	35	—
No	120	—

Secondary/registry result

Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol), AACE Target (Yes/no)

Time frame:Week 26

HbA1c <6.5% achievement

threshold achievement, improvement

LOINC 4548-4

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mgYes	60	—
No	94	—
PlaceboYes	12	—
No	143	—

Secondary/registry result

Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)

Time frame:Week 26

HbA1c <7.0% achievement

threshold achievement, improvement

componentsHbA1c <7.0% achievement, Severe hypoglycemia, Body weight, absolute change (kg)

LOINC 4548-4

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mgYes	78	—
No	76	—
PlaceboYes	27	—
No	128	—

Secondary/registry result

Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no)

Time frame:Week 26

threshold achievement, improvement

componentsHbA1c, change, Body weight, % change

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mgYes	60	—
No	94	—
PlaceboYes	12	—
No	143	—

Secondary/registry result

Time to Additional Anti-diabetic Medication

Time frame:Weeks 0-26

threshold achievement, event

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mg	12	—
Placebo	21	—

Hazard Ratio (HR)0.6495% CI0.34 – 1.23p=0.1834Regression, Cox

Secondary/registry result

Time to Rescue Medication

Time frame:Weeks 0-26

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mg	7	—
Placebo	16	—

Hazard Ratio (HR)0.4395% CI0.17 – 1.04p=0.0610Regression, Cox

Secondary/protocol endpoint

Change in FPG

Time frame:Week 0, week 26

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Participants Who Achieve HbA1c <7.0% (53 mmol/Mol), ADA Target (Yes/no)

Time frame:Week 26

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Secondary/protocol endpoint

Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol), AACE Target (Yes/no)

Time frame:Week 26

HbA1c <6.5% achievement

threshold achievement, improvement

LOINC 4548-4

Secondary/protocol endpoint

Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)

Time frame:Week 26

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Secondary/protocol endpoint

Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no)

Time frame:Week 26

threshold achievement, improvement

componentsHbA1c, change, Body weight, % change

Secondary/protocol endpoint

Time to Additional Anti-diabetic Medication

Time frame:Weeks 0-26

time to event, event

Secondary/protocol endpoint

Time to Rescue Medication

Time frame:Weeks 0-26

time to event, event

Renal / kidney

2 endpoints

Secondary/registry result

Change in Urinary Albumin to Creatinine Ratio (Ratio to Baseline)

Time frame:Week 0, week 26

uACR, change

ratio, improvement

LOINC 9318-7

Posted result

Group	Value (geometric_mean), Ratio	95% CI
Oral Semaglutide 14 mg	0.86	—
Placebo	1.19	—

Secondary/protocol endpoint

Change in Urinary Albumin to Creatinine Ratio (Ratio to Baseline)

Time frame:Week 0, week 26

uACR, change

ratio, improvement

LOINC 9318-7

Cardiometabolic biomarkers

14 endpoints

Secondary/registry result

Change in Total Cholesterol (Ratio to Baseline)

Time frame:Week 0, week 26

Total cholesterol, change

ratio, improvement

LOINC 2093-3

Posted result

Group	Value (geometric_mean), Ratio of total cholesterol	95% CI
Oral Semaglutide 14 mg	0.97	—
Placebo	1.00	—

Secondary/registry result

Change in LDL Cholesterol (Ratio to Baseline)

Time frame:Week 0, week 26

LDL-C, change

ratio, improvement

LOINC 13457-7

Posted result

Group	Value (geometric_mean), Ratio of LDL cholesterol	95% CI
Oral Semaglutide 14 mg	0.97	—
Placebo	1.00	—

Secondary/registry result

Change in HDL Cholesterol (Ratio to Baseline)

Time frame:Week 0, week 26

HDL-C, change

ratio, improvement

LOINC 2085-9

Posted result

Group	Value (geometric_mean), Ratio of HDL cholesterol	95% CI
Oral Semaglutide 14 mg	1.02	—
Placebo	1.02	—

Secondary/registry result

Change in Triglycerides (Ratio to Baseline)

Time frame:Week 0, week 26

Triglycerides, change

ratio, improvement

LOINC 2571-8

Posted result

Group	Value (geometric_mean), Ratio of triglycerides	95% CI
Oral Semaglutide 14 mg	0.87	—
Placebo	0.95	—

Secondary/registry result

Change in CRP (Ratio to Baseline)

Time frame:Week 0, week 26

hs-CRP, change

ratio, improvement

LOINC 30522-7

Posted result

Group	Value (geometric_mean), Ratio of CRP	95% CI
Oral Semaglutide 14 mg	0.86	—
Placebo	1.00	—

Secondary/registry result

Change in Pulse Rate

Time frame:Week 0, week 26

Heart rate, change

change from baseline, improvement

Posted result

Group	Value (mean), Beats/minute	95% CI
Oral Semaglutide 14 mg	1	—
Placebo	-1	—

Secondary/registry result

Change in Blood Pressure (Systolic and Diastolic Blood Pressure)

Time frame:Week 0, week 26

Systolic BP, change

change from baseline, improvement

componentsSystolic BP, change, Diastolic BP, change

LOINC 8480-6

Posted result

Group	Value (mean), mmHg	95% CI
Oral Semaglutide 14 mgSystolic blood pressure	-8	—
Diastolic blood pressure	-3	—
PlaceboSystolic blood pressure	0	—
Diastolic blood pressure	0	—

Secondary/protocol endpoint

Change in Total Cholesterol (Ratio to Baseline)

Time frame:Week 0, week 26

Total cholesterol, change

ratio, improvement

LOINC 2093-3

Secondary/protocol endpoint

Change in LDL Cholesterol (Ratio to Baseline)

Time frame:Week 0, week 26

LDL-C, change

ratio, improvement

LOINC 13457-7

Secondary/protocol endpoint

Change in HDL Cholesterol (Ratio to Baseline)

Time frame:Week 0, week 26

HDL-C, change

ratio, improvement

LOINC 2085-9

Secondary/protocol endpoint

Change in Triglycerides (Ratio to Baseline)

Time frame:Week 0, week 26

Triglycerides, change

ratio, improvement

LOINC 2571-8

Secondary/protocol endpoint

Change in CRP (Ratio to Baseline)

Time frame:Week 0, week 26

hs-CRP, change

ratio, improvement

LOINC 30522-7

Secondary/protocol endpoint

Change in Pulse Rate

Time frame:Week 0, week 26

Heart rate, change

change from baseline, improvement

Secondary/protocol endpoint

Change in Blood Pressure (Systolic and Diastolic Blood Pressure)

Time frame:Week 0, week 26

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Patient-reported / QoL

4 endpoints

Secondary/registry result

Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS)

Time frame:Week 0, week 26

SF-36 total

change from baseline, improvement

Posted result

Group	Value (mean), Score	95% CI
Oral Semaglutide 14 mg1) Physical functioning	0.71	—
2) Role functioning	1.97	—
3) Bodily pain	3.18	—
4) General health	0.18	—
5) Vitality	0.05	—
6) Social functioning	1.87	—
7) Role emotional	0.62	—
8) Mental health	0.34	—
Physical component summary (PCS)	1.78	—
Mental component summary (MCS)	0.26	—
Placebo1) Physical functioning	-0.41	—
2) Role functioning	-0.36	—
3) Bodily pain	-0.33	—
4) General health	-0.13	—
5) Vitality	0.56	—
6) Social functioning	-0.06	—
7) Role emotional	-1.18	—
8) Mental health	-0.19	—
Physical component summary (PCS)	-0.15	—
Mental component summary (MCS)	-0.32	—

Secondary/registry result

Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed)

Time frame:Week 0, week 26

change from baseline, improvement

Posted result

Group	Value (mean), Score	95% CI
Oral Semaglutide 14 mg1) Satisfaction with treatment	0.41	—
2) Feeling of unacceptably high blood sugars	-1.26	—
3) Feeling of unacceptably low blood sugars	0.11	—
4) Convenience of treatment	0.43	—
5) Flexibility of treatment	0.37	—
6) Satisfaction with understanding of diabetes	0.31	—
7) Recommending treatment to others	0.71	—
8) Satisfaction to continue with present treatment	0.58	—
Total treatment satisfaction	2.82	—
Placebo1) Satisfaction with treatment	0.74	—
2) Feeling of unacceptably high blood sugars	-0.30	—
3) Feeling of unacceptably low blood sugars	-0.32	—
4) Convenience of treatment	0.42	—
5) Flexibility of treatment	0.52	—
6) Satisfaction with understanding of diabetes	0.60	—
7) Recommending treatment to others	0.37	—
8) Satisfaction to continue with present treatment	0.47	—
Total treatment satisfaction	3.13	—

Secondary/protocol endpoint

Time frame:Week 0, week 26

SF-36 total

change from baseline, improvement

Secondary/protocol endpoint

Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed)

Time frame:Week 0, week 26

change from baseline, improvement

Safety / tolerability / PK

30 endpoints

Secondary/registry result

Number of TEAEs

Time frame:Weeks 0-31

Treatment-emergent AEs (any)

event count, event

Posted result

Group	Value (number), Events	95% CI
Oral Semaglutide 14 mg	463	—
Placebo	331	—

Secondary/registry result

Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes

Time frame:Weeks 0-31

Documented hypoglycemia

event count, event

componentsSevere hypoglycemia, Documented hypoglycemia

Posted result

Group	Value (number), Episodes	95% CI
Oral Semaglutide 14 mg	17	—
Placebo	3	—

Secondary/registry result

Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no)

Time frame:Weeks 0-31

Documented hypoglycemia

threshold achievement, event

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mg	9	—
Placebo	3	—

Secondary/registry result

Change in Amylase (Ratio to Baseline)

Time frame:Week 0, week 26

ratio, descriptive

Posted result

Group	Value (geometric_mean), Ratio of amylase	95% CI
Oral Semaglutide 14 mg	1.09	—
Placebo	0.99	—

Secondary/registry result

Change in Lipase (Ratio to Baseline)

Time frame:Week 0, week 26

ratio, descriptive

Posted result

Group	Value (geometric_mean), Ratio of lipase	95% CI
Oral Semaglutide 14 mg	1.16	—
Placebo	0.94	—

Secondary/registry result

Change in ECG

Time frame:Week 0, week 26

categorical status, descriptive

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mgNormal (week 0) to normal (week 26)	38	—
Normal (week 0) to abnormal NCS (week 26)	13	—
Normal (week 0) to abnormal CS (week 26)	1	—
Abnormal (week 0) NCS to normal (week 26)	12	—
Abnormal (week 0) NCS to abnormal NCS (week 26)	84	—
Abnormal (week 0) NCS to abnormal CS (week 26)	1	—
Abnormal (week 0) CS to normal (week 26)	0	—
Abnormal (week 0) CS to abnormal NCS (week 26)	1	—
Abnormal (week 0) CS to abnormal CS (week 26)	4	—
PlaceboNormal (week 0) to normal (week 26)	39	—
Normal (week 0) to abnormal NCS (week 26)	9	—
Normal (week 0) to abnormal CS (week 26)	0	—
Abnormal (week 0) NCS to normal (week 26)	13	—
Abnormal (week 0) NCS to abnormal NCS (week 26)	88	—
Abnormal (week 0) NCS to abnormal CS (week 26)	2	—
Abnormal (week 0) CS to normal (week 26)	0	—
Abnormal (week 0) CS to abnormal NCS (week 26)	0	—
Abnormal (week 0) CS to abnormal CS (week 26)	2	—

Secondary/registry result

Change in Physical Examination

Time frame:Week -2, week 26

descriptive

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mg1) Cardiovascular system (wk -2): Normal	107	—
1) Cardiovascular system (wk -2): Abnormal NCS	50	—
1) Cardiovascular system (wk -2): Abnormal CS	6	—
1) Cardiovascular system (wk 26): Normal	101	—
1) Cardiovascular system (wk 26): Abnormal NCS	48	—
1) Cardiovascular system (wk 26): Abnormal CS	6	—
2) Nervous system (wk -2): Normal	114	—
2) Nervous system (wk -2): Abnormal NCS	41	—
2) Nervous system (wk -2): Abnormal CS	8	—
2) Nervous system (wk 26): Normal	109	—
2) Nervous system (wk 26): Abnormal NCS	40	—
2) Nervous system (wk 26): Abnormal CS	6	—
3) Gastrointestinal system (wk -2): Normal	149	—
3) Gastrointestinal system (wk -2): Abnormal NCS	14	—
3) Gastrointestinal system (wk -2): Abnormal CS	0	—
3) Gastrointestinal system (wk 26): Normal	146	—
3) Gastrointestinal system (wk 26): Abnormal NCS	9	—
3) Gastrointestinal system (wk 26): Abnormal CS	0	—
4) General appearance (wk -2): Normal	133	—
4) General appearance (wk -2): Abnormal NCS	27	—
4) General appearance (wk -2): Abnormal CS	3	—
4) General appearance (wk 26): Normal	139	—
4) General appearance (wk 26): Abnormal NCS	15	—
4) General appearance (wk 26): Abnormal CS	1	—
5) Head, throat, neck (wk -2): Normal	151	—
5) Head, throat, neck (wk -2): Abnormal NCS	10	—
5) Head, throat, neck (wk -2): Abnormal CS	2	—
5) Head, throat, neck (wk 26): Normal	142	—
5) Head, throat, neck (wk 26): Abnormal NCS	10	—
5) Head, throat, neck (wk 26): Abnormal CS	3	—
6) Lymph node palpation (wk -2): Normal	161	—
6) Lymph node palpation (wk -2): Abnormal NCS	1	—
6) Lymph node palpation (wk -2): Abnormal CS	0	—
6) Lymph node palpation (wk 26): Normal	155	—
6) Lymph node palpation (wk 26): Abnormal NCS	0	—
6) Lymph node palpation (wk 26): Abnormal CS	0	—
7) Musculoskeletal system (wk -2): Normal	131	—
7) Musculoskeletal system (wk -2): Abnormal NCS	27	—
7) Musculoskeletal system (wk -2): Abnormal CS	5	—
7) Musculoskeletal system (wk 26): Normal	131	—
7) Musculoskeletal system (wk 26): Abnormal NCS	22	—
7) Musculoskeletal system (wk 26): Abnormal CS	2	—
8) Respiratory system (wk -2): Normal	154	—
8) Respiratory system (wk -2): Abnormal NCS	9	—
8) Respiratory system (wk -2): Abnormal CS	0	—
8) Respiratory system (wk 26): Normal	151	—
8) Respiratory system (wk 26): Abnormal NCS	4	—
8) Respiratory system (wk 26): Abnormal CS	0	—
9) Skin (wk -2): Normal	129	—
9) Skin (wk -2): Abnormal NCS	33	—
9) Skin (wk -2): Abnormal CS	1	—
9) Skin (wk 26): Normal	128	—
9) Skin (wk 26): Abnormal NCS	23	—
9) Skin (wk 26): Abnormal CS	4	—
10) Thyroid gland (wk -2): Normal	150	—
10) Thyroid gland (wk -2): Abnormal NCS	12	—
10) Thyroid gland (wk -2): Abnormal CS	1	—
10) Thyroid gland (wk 26): Normal	142	—
10) Thyroid gland (wk 26): Abnormal NCS	12	—
10) Thyroid gland (wk 26): Abnormal CS	1	—
Placebo1) Cardiovascular system (wk -2): Normal	103	—
1) Cardiovascular system (wk -2): Abnormal NCS	55	—
1) Cardiovascular system (wk -2): Abnormal CS	3	—
1) Cardiovascular system (wk 26): Normal	104	—
1) Cardiovascular system (wk 26): Abnormal NCS	47	—
1) Cardiovascular system (wk 26): Abnormal CS	3	—
2) Nervous system (wk -2): Normal	116	—
2) Nervous system (wk -2): Abnormal NCS	45	—
2) Nervous system (wk -2): Abnormal CS	0	—
2) Nervous system (wk 26): Normal	115	—
2) Nervous system (wk 26): Abnormal NCS	39	—
2) Nervous system (wk 26): Abnormal CS	0	—
3) Gastrointestinal system (wk -2): Normal	152	—
3) Gastrointestinal system (wk -2): Abnormal NCS	9	—
3) Gastrointestinal system (wk -2): Abnormal CS	0	—
3) Gastrointestinal system (wk 26): Normal	145	—
3) Gastrointestinal system (wk 26): Abnormal NCS	7	—
3) Gastrointestinal system (wk 26): Abnormal CS	1	—
4) General appearance (wk -2): Normal	138	—
4) General appearance (wk -2): Abnormal NCS	20	—
4) General appearance (wk -2): Abnormal CS	3	—
4) General appearance (wk 26): Normal	137	—
4) General appearance (wk 26): Abnormal NCS	16	—
4) General appearance (wk 26): Abnormal CS	1	—
5) Head, throat, neck (wk -2): Normal	143	—
5) Head, throat, neck (wk -2): Abnormal NCS	15	—
5) Head, throat, neck (wk -2): Abnormal CS	3	—
5) Head, throat, neck (wk 26): Normal	139	—
5) Head, throat, neck (wk 26): Abnormal NCS	11	—
5) Head, throat, neck (wk 26): Abnormal CS	3	—
6) Lymph node palpation (wk -2): Normal	161	—
6) Lymph node palpation (wk -2): Abnormal NCS	0	—
6) Lymph node palpation (wk -2): Abnormal CS	0	—
6) Lymph node palpation (wk 26): Normal	154	—
6) Lymph node palpation (wk 26): Abnormal NCS	0	—
6) Lymph node palpation (wk 26): Abnormal CS	0	—
7) Musculoskeletal system (wk -2): Normal	135	—
7) Musculoskeletal system (wk -2): Abnormal NCS	24	—
7) Musculoskeletal system (wk -2): Abnormal CS	2	—
7) Musculoskeletal system (wk 26): Normal	130	—
7) Musculoskeletal system (wk 26): Abnormal NCS	21	—
7) Musculoskeletal system (wk 26): Abnormal CS	2	—
8) Respiratory system (wk -2): Normal	150	—
8) Respiratory system (wk -2): Abnormal NCS	8	—
8) Respiratory system (wk -2): Abnormal CS	3	—
8) Respiratory system (wk 26): Normal	147	—
8) Respiratory system (wk 26): Abnormal NCS	5	—
8) Respiratory system (wk 26): Abnormal CS	2	—
9) Skin (wk -2): Normal	129	—
9) Skin (wk -2): Abnormal NCS	32	—
9) Skin (wk -2): Abnormal CS	0	—
9) Skin (wk 26): Normal	136	—
9) Skin (wk 26): Abnormal NCS	18	—
9) Skin (wk 26): Abnormal CS	0	—
10) Thyroid gland (wk -2): Normal	146	—
10) Thyroid gland (wk -2): Abnormal NCS	15	—
10) Thyroid gland (wk -2): Abnormal CS	0	—
10) Thyroid gland (wk 26): Normal	140	—
10) Thyroid gland (wk 26): Abnormal NCS	14	—
10) Thyroid gland (wk 26): Abnormal CS	0	—

Secondary/registry result

Occurrence of Anti-semaglutide Binding Antibodies (Yes/no)

Time frame:Weeks 0-31

Immunogenicity (ADA)

categorical status, event

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mg	1	—

Secondary/registry result

Occurrence of Anti-semaglutide Neutralising Antibodies (Yes/no)

Time frame:Weeks 0-31

Immunogenicity (ADA)

categorical status, event

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mg	0	—

Secondary/registry result

Occurrence of Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1 (Yes/no)

Time frame:Weeks 0-31

Immunogenicity (ADA)

threshold achievement, event

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mg	1	—

Secondary/registry result

Occurrence of Anti-semaglutide Neutralising Antibodies Cross Reacting With Native GLP-1 (Yes/no)

Time frame:Weeks 0-31

Immunogenicity (ADA)

threshold achievement, event

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mg	0	—

Secondary/registry result

Anti-semaglutide Binding Antibody Levels

Time frame:Weeks 0-31

Immunogenicity (ADA)

descriptive

Posted result

Group	Value (mean), %B/T	95% CI
Oral Semaglutide 14 mgWeek 4	3.1	—
Week 31	2.2	—

Secondary/registry result

Semaglutide Plasma Concentrations for Population PK Analyses

Time frame:Weeks 0-26

Plasma concentration (steady state)

concentration, descriptive

Posted result

Group	Value (geometric_mean), Nanomoles per litre (nmol/L)	95% CI
Oral Semaglutide 14 mgWeek 4	1.8	—
Week 8	5.2	—
Week 14	9.4	—
Week 26	6.9	—

Secondary/registry result

SNAC Plasma Concentrations

Time frame:Weeks 0-26

Plasma concentration (steady state)

concentration, descriptive

Posted result

Group	Value (geometric_mean), Nanograms per milliliter (ng/mL)	95% CI
Oral Semaglutide 14 mgWeek 4: 25 minutes post-dose	578	—
Week 4: 40 minutes post-dose	364	—
Week 14: 25 minutes post-dose	418	—
Week 14: 40 minutes post-dose	330	—
Week 26: 25 minutes post-dose	435	—
Week 26: 40 minutes post-dose	288	—

Secondary/registry result

Change in Urinalysis

Time frame:Week -2, week 26

descriptive

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mgLeucocytes (wk 0): Negative	121	—
Leucocytes (wk 0): Trace	14	—
Leucocytes (wk 0): Small	8	—
Leucocytes (wk 0): Moderate	10	—
Leucocytes (wk 0): Large	5	—
Leucocytes (wk 26): Negative	91	—
Leucocytes (wk 26): Trace	9	—
Leucocytes (wk 26): Small	13	—
Leucocytes (wk 26): Moderate	10	—
Leucocytes (wk 26): Large	6	—
Erythrocytes (wk 0): Negative	147	—
Erythrocytes (wk 0): Trace	4	—
Erythrocytes (wk 0): Small	4	—
Erythrocytes (wk 0): Moderate	1	—
Erythrocytes (wk 0): Large	2	—
Erythrocytes (wk 26): Negative	115	—
Erythrocytes (wk 26): Trace	6	—
Erythrocytes (wk 26): Small	6	—
Erythrocytes (wk 26): Moderate	2	—
Erythrocytes (wk 26): Large	0	—
Nitrit (wk 0): Negative	149	—
Nitrit (wk 0): Positive	9	—
Nitrit (wk 26): Negative	118	—
Nitrit (wk 26): Positive	11	—
PlaceboLeucocytes (wk 0): Negative	122	—
Leucocytes (wk 0): Trace	7	—
Leucocytes (wk 0): Small	12	—
Leucocytes (wk 0): Moderate	9	—
Leucocytes (wk 0): Large	5	—
Leucocytes (wk 26): Negative	103	—
Leucocytes (wk 26): Trace	11	—
Leucocytes (wk 26): Small	10	—
Leucocytes (wk 26): Moderate	10	—
Leucocytes (wk 26): Large	4	—
Erythrocytes (wk 0): Negative	137	—
Erythrocytes (wk 0): Trace	10	—
Erythrocytes (wk 0): Small	4	—
Erythrocytes (wk 0): Moderate	1	—
Erythrocytes (wk 0): Large	3	—
Erythrocytes (wk 26): Negative	122	—
Erythrocytes (wk 26): Trace	7	—
Erythrocytes (wk 26): Small	3	—
Erythrocytes (wk 26): Moderate	4	—
Erythrocytes (wk 26): Large	2	—
Nitrit (wk 0): Negative	146	—
Nitrit (wk 0): Positive	9	—
Nitrit (wk 26): Negative	126	—
Nitrit (wk 26): Positive	12	—

Secondary/protocol endpoint

Number of TEAEs

Time frame:Weeks 0-31

Treatment-emergent AEs (any)

event count, event

Secondary/protocol endpoint

Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes

Time frame:Weeks 0-31

Documented hypoglycemia

event count, event

componentsSevere hypoglycemia, Documented hypoglycemia

Secondary/protocol endpoint

Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no)

Time frame:Weeks 0-31

Severe hypoglycemia

threshold achievement, event

componentsSevere hypoglycemia, Documented hypoglycemia

Secondary/protocol endpoint

Change in Amylase (Ratio to Baseline)

Time frame:Week 0, week 26

ratio, descriptive

Secondary/protocol endpoint

Change in Lipase (Ratio to Baseline)

Time frame:Week 0, week 26

ratio, descriptive

Secondary/protocol endpoint

Change in ECG

Time frame:Week 0, week 26

categorical status, descriptive

Secondary/protocol endpoint

Change in Physical Examination

Time frame:Week -2, week 26

descriptive

Secondary/protocol endpoint

Occurrence of Anti-semaglutide Binding Antibodies (Yes/no)

Time frame:Weeks 0-31

Immunogenicity (ADA)

categorical status, event

Secondary/protocol endpoint

Occurrence of Anti-semaglutide Neutralising Antibodies (Yes/no)

Time frame:Weeks 0-31

Immunogenicity (ADA)

categorical status, event

Secondary/protocol endpoint

Occurrence of Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1 (Yes/no)

Time frame:Weeks 0-31

Immunogenicity (ADA)

categorical status, event

Secondary/protocol endpoint

Occurrence of Anti-semaglutide Neutralising Antibodies Cross Reacting With Native GLP-1 (Yes/no)

Time frame:Weeks 0-31

Immunogenicity (ADA)

categorical status, event

Secondary/protocol endpoint

Anti-semaglutide Binding Antibody Levels

Time frame:Weeks 0-31

Immunogenicity (ADA)

descriptive

Secondary/protocol endpoint

Semaglutide Plasma Concentrations for Population PK Analyses

Time frame:Weeks 0-26

Plasma concentration (steady state)

concentration, descriptive

Secondary/protocol endpoint

SNAC Plasma Concentrations

Time frame:Weeks 0-26

Plasma concentration (steady state)

concentration, descriptive

Secondary/protocol endpoint

Change in Urinalysis

Time frame:Week -2, week 26

descriptive

Other clinical outcomes

2 endpoints

Secondary/registry result

Change in Eye Examination

Time frame:Week -2, week 26

categorical status, descriptive

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mgLeft eye (week -2): Normal	57	—
Left eye (week -2): Abnormal NCS	98	—
Left eye (week -2): Abnormal CS	8	—
Left eye (week 26): Normal	54	—
Left eye (week 26): Abnormal NCS	92	—
Left eye (week 26): Abnormal CS	5	—
Right eye (week -2): Normal	59	—
Right eye (week -2): Abnormal NCS	97	—
Right eye (week -2): Abnormal CS	7	—
Right eye (week 26): Normal	52	—
Right eye (week 26): Abnormal NCS	97	—
Right eye (week 26): Abnormal CS	2	—
PlaceboLeft eye (week -2): Normal	66	—
Left eye (week -2): Abnormal NCS	93	—
Left eye (week -2): Abnormal CS	0	—
Left eye (week 26): Normal	55	—
Left eye (week 26): Abnormal NCS	95	—
Left eye (week 26): Abnormal CS	0	—
Right eye (week -2): Normal	66	—
Right eye (week -2): Abnormal NCS	93	—
Right eye (week -2): Abnormal CS	0	—
Right eye (week 26): Normal	55	—
Right eye (week 26): Abnormal NCS	95	—
Right eye (week 26): Abnormal CS	0	—

Secondary/protocol endpoint

Change in Eye Examination

Time frame:Week -2, week 26

categorical status, descriptive

Publications (7)

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

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
Impact of semaglutide on high-sensitivity C-reactive protein: exploratory patient-level analyses of SUSTAIN and PIONEER randomized clinical trials.
Cardiovascular diabetology2022 Sep 2PMID36056351doi:10.1186/s12933-022-01585-7via clinicaltrials gov reference derived + pubmed nct search
Oral Semaglutide Reduces HbA(1c) and Body Weight in Patients with Type 2 Diabetes Regardless of Background Glucose-Lowering Medication: PIONEER Subgroup Analyses.
Diabetes therapy : research, treatment and education of diabetes and related disorders2021 Apr (month)PMID33660198doi:10.1007/s13300-020-00994-9via clinicaltrials gov reference derived + pubmed nct search
Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials.
Cardiovascular diabetology2020 Sep 30PMID32998732doi:10.1186/s12933-020-01106-4via clinicaltrials gov reference derived + pubmed nct search
Efficacy, safety and cardiovascular outcomes of once-daily oral semaglutide in patients with type 2 diabetes: The PIONEER programme.
Diabetes, obesity & metabolism2020 Aug (month)PMID32267058doi:10.1111/dom.14054via clinicaltrials gov reference derived + pubmed nct search
Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk.
Diabetes, obesity & metabolism2020 Mar (month)PMID31903692doi:10.1111/dom.13955via clinicaltrials gov reference derived + pubmed nct search
Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): a placebo-controlled, randomised, phase 3a trial.
The lancet. Diabetes & endocrinology2019 Jul (month)PMID31189517doi:10.1016/S2213-8587(19)30192-5via CT.gov reference + 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.