← Trials/Trial dossier/NCT02863328

PIONEER 2

CompletedPhase 3Results posted

Efficacy and Safety of Oral Semaglutide Versus Empagliflozin in Subjects With Type 2 Diabetes Mellitus

Lead sponsor

Novo Nordisk A/S

Asset

Semaglutide

Oral · GLP-1 agonist

Listed sites

106

Recruiting sites

—

Enrollment

822

actual

Study population

Type 2 diabetes

Key I/E criterion

•HbA1c 7-10.5%

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 IDNCT02863328

Org study IDNN9924-4223

Secondary ID2015-005209-36

Secondary IDU1111-1176-6006World Health Organization (WHO)

Timeline

Milestones

Study start2016-08-10actual

Study first posted2016-08-11estimated

Primary completion2017-08-01actual

Study completion2018-03-08actual

Results first posted2019-12-24actual

Last update posted2022-07-20actual

Assets

Investigational agents

Semaglutide

Study populations

Who this study enrolls

Type 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 at least 90 days prior to day of screening

•HbA1c (glycosylated haemoglobin) of 7.0-10.5 % (53-91 mmol/mol) (both inclusive)

•Stable daily dose of metformin (at least 1500 mg or maximum tolerated dose as documented in the subject medical record) at least 90 days prior to the day of screening

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

•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 ALT (alanine aminotransferase) above 2.5 x upper normal limit

•Renal impairment defined as Estimated Glomerular Filtration Rate below 60 mL/min/1.73 m^2 as per Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI)

•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

•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)

•History of diabetic ketoacidosis

Endpoints (100)

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

Glycemic / diabetes

Safety / tolerability / PK

Cardiometabolic biomarkers

Weight & body composition

Patient-reported / QoL

Other (unclassified)

Other clinical outcomes

Weight & body composition

14 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), Kilogram (Kg)	95% CI
Oral Semaglutide 14 mgIn-trial	-3.9	—
On-treatment without rescue medication	-4.3	—
Empagliflozin 25 mgIn-trial	-3.8	—
On-treatment without rescue medication	-3.9	—

Treatment difference-0.195% CI-0.7 – 0.5p= 0.7593Pattern mixture model

Treatment difference-0.495% CI-1.0 – 0.1p= 0.1358MMRM

Secondary/registry result

Change in Body Weight (kg)

Time frame:Week 0, week 52

Body weight, absolute change (kg)

change from baseline, improvement

Posted result

Group	Value (mean), Kg	95% CI
Oral Semaglutide 14 mg	-4.0	—
Empagliflozin 25 mg	-3.7	—

Secondary/registry result

Change in Body Weight (%)

Time frame:Week 0, week 26, week 52

Body weight, % change

percent change from baseline, improvement

Posted result

Group	Value (mean), Percentage change	95% CI
Oral Semaglutide 14 mgWeek 26	-4.34	—
Week 52	-4.38	—
Empagliflozin 25 mgWeek 26	-4.14	—
Week 52	-4.09	—

Secondary/registry result

Change in Body Mass Index

Time frame:Week 0, week 26, week 52

BMI, change

change from baseline, improvement

Posted result

Group	Value (mean), Kilograms per square meter (kg/m^2)	95% CI
Oral Semaglutide 14 mgWeek 26	-1.4	—
Week 52	-1.5	—
Empagliflozin 25 mgWeek 26	-1.4	—
Week 52	-1.4	—

Secondary/registry result

Change in Waist Circumference

Time frame:Week 0, week 26, week 52

Waist circumference, change

change from baseline, improvement

Posted result

Group	Value (mean), Centimetre (cm)	95% CI
Oral Semaglutide 14 mgWeek 26	-3.9	—
Week 52	-3.7	—
Empagliflozin 25 mgWeek 26	-2.9	—
Week 52	-2.9	—

Secondary/registry result

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

Time frame:Week 26 and week 52

≥5% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mgWeek 26	162	—
Week 26	231	—
Week 52	156	—
Week 52	230	—
Empagliflozin 25 mgWeek 26	143	—
Week 26	253	—
Week 52	150	—
Week 52	233	—

Secondary/registry result

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

Time frame:Week 26 and week 52

≥10% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mgWeek 26	49	—
Week 26	344	—
Week 52	58	—
Week 52	328	—
Empagliflozin 25 mgWeek 26	27	—
Week 26	369	—
Week 52	30	—
Week 52	353	—

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 (kg)

Time frame:Week 0, week 52

Body weight, absolute change (kg)

change from baseline, improvement

Secondary/protocol endpoint

Change in Body Weight (%)

Time frame:Week 0, week 26, week 52

Body weight, % change

percent change from baseline, improvement

Secondary/protocol endpoint

Change in Body Mass Index

Time frame:Week 0, week 26, week 52

BMI, change

change from baseline, improvement

Secondary/protocol endpoint

Change in Waist Circumference

Time frame:Week 0, week 26, week 52

Waist circumference, change

change from baseline, improvement

Secondary/protocol endpoint

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

Time frame:Week 26 and week 52

≥5% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

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

Time frame:Week 26 and week 52

≥10% weight-loss responders

threshold achievement, improvement

Glycemic / diabetes

31 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-point of HbA1c	95% CI
Oral Semaglutide 14 mgIn-trial	-1.3	—
On-treatment without rescue medication	-1.5	—
Empagliflozin 25 mgIn-trial	-0.9	—
On-treatment without rescue medication	-0.9	—

Treatment difference-0.495% CI-0.6 – -0.3p< 0.0001Pattern mixture model

Treatment difference-0.595% CI-0.7 – -0.4p<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 HbA1c (%)

Time frame:Week 0, week 52

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

Group	Value (mean), Percentage of HbA1c	95% CI
Oral Semaglutide 14 mg	-1.3	—
Empagliflozin 25 mg	-0.9	—

Secondary/registry result

Change in Fasting Plasma Glucose

Time frame:Week 0, week 26, week 52

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

Group	Value (mean), Millimoles per liter (mmol/L)	95% CI
Oral Semaglutide 14 mgWeek 26	-2.01	—
Week 52	-2.04	—
Empagliflozin 25 mgWeek 26	-2.08	—
Week 52	-2.14	—

Secondary/registry result

Change in SMPG : Mean of the 7-point Profile

Time frame:Week 0, week 26 and week 52

Postprandial glucose

change from baseline, improvement

Posted result

Group	Value (mean), mmol/L	95% CI
Oral Semaglutide 14 mgWeek 26	-2.3	—
Week 52	-2.3	—
Empagliflozin 25 mgWeek 26	-1.9	—
Week 52	-2.1	—

Secondary/registry result

Change in SMPG : Mean Postprandial Increment Over All Meals

Time frame:Week 0, week 26 and week 52

Postprandial glucose

change from baseline, improvement

Posted result

Group	Value (mean), mmol/L	95% CI
Oral Semaglutide 14 mgWeek 26	-0.5	—
Week 52	-0.6	—
Empagliflozin 25 mgWeek 26	-0.4	—
Week 52	-0.4	—

Secondary/registry result

Change in Fasting C-peptide (Ratio to Baseline)

Time frame:Week 0, week 26 and week 52

C-peptide AUC

ratio, improvement

Posted result

Group	Value (geometric_mean), Ratio of C-peptide	95% CI
Oral Semaglutide 14 mgweek 26	1.10	—
week 52	1.09	—
Empagliflozin 25 mgweek 26	0.89	—
week 52	0.92	—

Secondary/registry result

Change in Fasting Insulin (Ratio to Baseline)

Time frame:Week 0, week 26 and week 52

ratio, improvement

Posted result

Group	Value (geometric_mean), Ratio of insulin	95% CI
Oral Semaglutide 14 mgWeek 26	1.06	—
Week 52	1.03	—
Empagliflozin 25 mgWeek 26	0.77	—
Week 52	0.77	—

Secondary/registry result/low confidence

Change in Fasting Pro-insulin (Ratio to Baseline)

Time frame:Week 0, week 26 and week 52

ratio, improvement

Posted result

Group	Value (geometric_mean), Ratio of pro-insulin	95% CI
Oral Semaglutide 14 mgWeek 26	0.72	—
Week 52	0.74	—
Empagliflozin 25 mgWeek 26	0.66	—
Week 52	0.69	—

Secondary/registry result

Change in Fasting Glucagon (Ratio to Baseline)

Time frame:Week 0, week 26 and week 52

ratio, improvement

Posted result

Group	Value (geometric_mean), Ratio of glucagon	95% CI
Oral Semaglutide 14 mgWeek 26	0.91	—
Week 52	0.89	—
Empagliflozin 25 mgWeek 26	1.01	—
Week 52	0.95	—

Secondary/registry result

Change in HOMA-IR (Ratio to Baseline)

Time frame:Week 0, week 26 and week 52

HOMA-IR (insulin sensitivity)

ratio, improvement

Posted result

Group	Value (geometric_mean), Ratio of HOMA-IR	95% CI
Oral Semaglutide 14 mgWeek 26	0.83	—
Week 52	0.81	—
Empagliflozin 25 mgWeek 26	0.61	—
Week 52	0.60	—

Secondary/registry result

Change in HOMA-B (Ratio to Baseline)

Time frame:Week 0, week 26 and week 52

ratio, improvement

Posted result

Group	Value (geometric_mean), Ratio of HOMA-B	95% CI
Oral Semaglutide 14 mgWeek 26	1.67	—
Week 52	1.66	—
Empagliflozin 25 mgWeek 26	1.16	—
Week 52	1.17	—

Secondary/registry result

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

Time frame:Week 26 and week 52

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mgWeek 26	262	—
Week 26	130	—
Week 52	254	—
Week 52	130	—
Empagliflozin 25 mgWeek 26	158	—
Week 26	237	—
Week 52	165	—
Week 52	217	—

Secondary/registry result

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

Time frame:Week 26 and week 52

HbA1c <6.5% achievement

threshold achievement, improvement

LOINC 4548-4

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mgWeek 26	186	—
Week 26	206	—
Week 52	182	—
Week 52	202	—
Empagliflozin 25 mgWeek 26	68	—
Week 26	327	—
Week 52	83	—
Week 52	299	—

Secondary/registry result/low confidence

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 and week 52

threshold achievement, improvement

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

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mgWeek 26	237	—
Week 26	155	—
Week 52	214	—
Week 52	170	—
Empagliflozin 25 mgWeek 26	141	—
Week 26	254	—
Week 52	149	—
Week 52	233	—

Secondary/registry result

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

Time frame:Week 26 and week 52

threshold achievement, improvement

componentsHbA1c, change, Body weight, % change

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mgweek 26	177	—
week 26	215	—
week 52	164	—
week 52	220	—
Empagliflozin 25 mgweek 26	111	—
week 26	284	—
week 52	101	—
week 52	281	—

Secondary/registry result

Time to Additional Anti-diabetic Medication

Time frame:Weeks 0-52

threshold achievement, event

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mgWeek 0-26	17	—
Week 0-52	52	—
Empagliflozin 25 mgWeek 0-26	13	—
Week 0-52	56	—

Hazard Ratio (HR)0.8595% CI0.60 – 1.20p0.3552Regression, Cox

Secondary/registry result

Time to Rescue Medication

Time frame:Weeks 0-52

time to event, event

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mgWeek 0-26	8	—
Week 0-52	31	—
Empagliflozin 25 mgWeek 0-26	5	—
Week 0-52	44	—

Hazard Ratio (HR)0.7595% CI0.47 – 1.19p0.2250Cox proportional hazards model

Secondary/protocol endpoint

Change in HbA1c (%)

Time frame:Week 0, week 52

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/protocol endpoint

Change in Fasting Plasma Glucose

Time frame:Week 0, week 26, week 52

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Change in SMPG : Mean of the 7-point Profile

Time frame:Week 0, week 26 and week 52

Postprandial glucose

change from baseline, improvement

Secondary/protocol endpoint

Change in SMPG : Mean Postprandial Increment Over All Meals

Time frame:Week 0, week 26 and week 52

Postprandial glucose

change from baseline, improvement

Secondary/protocol endpoint

Change in Fasting C-peptide (Ratio to Baseline)

Time frame:Week 0, week 26 and week 52

C-peptide AUC

ratio, improvement

Secondary/protocol endpoint

Change in Fasting Insulin (Ratio to Baseline)

Time frame:Week 0, week 26 and week 52

ratio, improvement

Secondary/protocol endpoint

Change in HOMA-IR (Ratio to Baseline)

Time frame:Week 0, week 26 and week 52

HOMA-IR (insulin sensitivity)

percent change from baseline, improvement

Secondary/protocol endpoint

Change in HOMA-B (Ratio to Baseline)

Time frame:Week 0, week 26 and week 52

ratio, improvement

Secondary/protocol endpoint

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

Time frame:Week 26 and week 52

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 and week 52

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 and week 52

HbA1c <7.0% achievement

threshold achievement, improvement

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

LOINC 4548-4

Secondary/protocol endpoint

Time to Additional Anti-diabetic Medication

Time frame:Weeks 0-52

event count, event

Secondary/protocol endpoint

Time to Rescue Medication

Time frame:Weeks 0-52

time to event, event

Cardiometabolic biomarkers

18 endpoints

Secondary/registry result

Change in C-reactive Protein (Ratio to Baseline)

Time frame:Week 0, week 26 and week 52

hs-CRP, change

ratio, improvement

LOINC 30522-7

Posted result

Group	Value (geometric_mean), Ratio of C-reactive protein	95% CI
Oral Semaglutide 14 mgWeek 26	0.69	—
Week 52	0.68	—
Empagliflozin 25 mgWeek 26	0.98	—
Week 52	0.90	—

Secondary/registry result

Change in Fasting Total Cholesterol (Ratio to Baseline)

Time frame:Week 0, week 26 and week 52

Total cholesterol, change

ratio, improvement

LOINC 2093-3

Posted result

Group	Value (geometric_mean), Ratio of total cholesterol	95% CI
Oral Semaglutide 14 mgWeek 26	0.96	—
Week 52	0.97	—
Empagliflozin 25 mgWeek 26	1.02	—
Week 52	1.01	—

Secondary/registry result

Change in Fasting LDL Cholesterol (Ratio to Baseline)

Time frame:Week 0, week 26 and week 52

LDL-C, change

ratio, improvement

LOINC 13457-7

Posted result

Group	Value (geometric_mean), Ratio of LDL cholesterol	95% CI
Oral Semaglutide 14 mgWeek 26	0.96	—
Week 52	0.97	—
Empagliflozin 25 mgWeek 26	1.03	—
Week 52	1.03	—

Secondary/registry result

Change in Fasting HDL Cholesterol (Ratio to Baseline)

Time frame:Week 0, week 26 and week 52

HDL-C, change

ratio, improvement

LOINC 2085-9

Posted result

Group	Value (geometric_mean), Ratio of HDL cholesterol	95% CI
Oral Semaglutide 14 mgWeek 26	1.01	—
Week 52	1.01	—
Empagliflozin 25 mgWeek 26	1.07	—
Week 52	1.06	—

Secondary/registry result

Change in Fasting VLDL Cholesterol (Ratio to Baseline)

Time frame:Week 0, week 26 and week 52

VLDL, change

ratio, improvement

Posted result

Group	Value (geometric_mean), Ratio of VLDL cholesterol	95% CI
Oral Semaglutide 14 mgWeek 26	0.89	—
Week 52	0.89	—
Empagliflozin 25 mgWeek 26	0.91	—
Week 52	0.90	—

Secondary/registry result

Change in Fasting Free Fatty Acids (Ratio to Baseline)

Time frame:Week 0, week 26 and week 52

Free fatty acids, change

ratio, improvement

Posted result

Group	Value (geometric_mean), Ratio of FFA	95% CI
Oral Semaglutide 14 mgWeek 26	0.95	—
Week 52	0.88	—
Empagliflozin 25 mgWeek 26	1.05	—
Week 52	0.97	—

Secondary/registry result

Change in Fasting Triglycerides (Ratio to Baseline)

Time frame:Week 0, week 26 and week 52

Triglycerides, change

ratio, improvement

LOINC 2571-8

Posted result

Group	Value (geometric_mean), Ratio of triglycerides	95% CI
Oral Semaglutide 14 mgWeek 26	0.88	—
Week 52	0.89	—
Empagliflozin 25 mgWeek 26	0.90	—
Week 52	0.90	—

Secondary/registry result

Change in Pulse Rate

Time frame:Week 0, week 26, week 52

Heart rate, change

change from baseline, improvement

Posted result

Group	Value (mean), Beats/minute	95% CI
Oral Semaglutide 14 mgWeek 26	1	—
Week 52	1	—
Empagliflozin 25 mgWeek 26	-2	—
Week 52	-2	—

Secondary/registry result

Change in Blood Pressure (Systolic and Diastolic Blood Pressure)

Time frame:Week 0, week 26, week 52

change from baseline, improvement

Posted result

Group	Value (mean), Millimeters of mercury (mmHg)	95% CI
Oral Semaglutide 14 mgSBP, week 26	-5	—
SBP, week 52	-5	—
DBP, week 26	-2	—
DBP, week 52	-3	—
Empagliflozin 25 mgSBP, week 26	-5	—
SBP, week 52	-4	—
DBP, week 26	-3	—
DBP, week 52	-3	—

Secondary/protocol endpoint

Change in C-reactive Protein (Ratio to Baseline)

Time frame:Week 0, week 26 and week 52

hs-CRP, change

ratio, improvement

LOINC 30522-7

Secondary/protocol endpoint

Change in Fasting Total Cholesterol (Ratio to Baseline)

Time frame:Week 0, week 26 and week 52

Total cholesterol, change

ratio, improvement

LOINC 2093-3

Secondary/protocol endpoint

Change in Fasting LDL Cholesterol (Ratio to Baseline)

Time frame:Week 0, week 26 and week 52

LDL-C, change

ratio, improvement

LOINC 13457-7

Secondary/protocol endpoint

Change in Fasting HDL Cholesterol (Ratio to Baseline)

Time frame:Week 0, week 26 and week 52

HDL-C, change

ratio, improvement

LOINC 2085-9

Secondary/protocol endpoint

Change in Fasting VLDL Cholesterol (Ratio to Baseline)

Time frame:Week 0, week 26 and week 52

VLDL, change

ratio, improvement

Secondary/protocol endpoint

Change in Fasting Free Fatty Acids (Ratio to Baseline)

Time frame:Week 0, week 26 and week 52

Free fatty acids, change

ratio, improvement

Secondary/protocol endpoint

Change in Fasting Triglycerides (Ratio to Baseline)

Time frame:Week 0, week 26 and week 52

Triglycerides, change

ratio, improvement

LOINC 2571-8

Secondary/protocol endpoint

Change in Pulse Rate

Time frame:Week 0, week 26, week 52

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, week 52

change from baseline, improvement

componentsSystolic BP, change, Diastolic BP, change

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, week 52

SF-36 total

change from baseline, improvement

Posted result

Group	Value (mean), Score on a scale	95% CI
Oral Semaglutide 14 mgWeek 26: Physical Functioning	0.87	—
Week 52: Physical Functioning	0.57	—
Week 26: Role functioning	0.07	—
Week 52: Role functioning	-0.61	—
Week 26: Bodily pain	-0.32	—
Week 52: Bodily pain	-0.33	—
Week 26: General health	2.26	—
Week 52: General health	2.47	—
Week 26: Vitality	0.66	—
Week 52: Vitality	0.83	—
Week 26: Social functioning	0.50	—
Week 52: Social functioning	-0.18	—
Week 26: Role emotional	0.67	—
Week 52: Role emotional	0.30	—
Week 26: Mental health	0.94	—
Week 52: Mental health	0.29	—
Week 26: PCS	0.53	—
Week 52: PCS	0.44	—
Week 26: MCS	0.83	—
Week 52: MCS	0.35	—
Empagliflozin 25 mgWeek 26: Physical Functioning	0.99	—
Week 52: Physical Functioning	0.84	—
Week 26: Role functioning	0.56	—
Week 52: Role functioning	0.52	—
Week 26: Bodily pain	1.04	—
Week 52: Bodily pain	1.20	—
Week 26: General health	1.36	—
Week 52: General health	1.86	—
Week 26: Vitality	0.49	—
Week 52: Vitality	1.15	—
Week 26: Social functioning	-0.54	—
Week 52: Social functioning	-0.54	—
Week 26: Role emotional	0.53	—
Week 52: Role emotional	0.42	—
Week 26: Mental health	-0.03	—
Week 52: Mental health	-0.03	—
Week 26: PCS	1.21	—
Week 52: PCS	1.36	—
Week 26: MCS	-0.23	—
Week 52: MCS	-0.09	—

Secondary/registry result

Change in CoEQ: Scores From the 4 Domains and the 19 Items

Time frame:Week 0, week 26, week 52

change from baseline, improvement

Posted result

Group	Value (mean), Score on a scale	95% CI
Oral Semaglutide 14 mgWeek 26: Craving control	0.46	—
Week 52: Craving control	0.44	—
Week 26: Positive Mood	0.08	—
Week 52: Positive Mood	0.15	—
Week 26: Craving for Savoury	-0.68	—
Week 52: Craving for Savoury	-0.66	—
Week 26: Craving for Sweet	-0.25	—
Week 52: Craving for Sweet	-0.21	—
Week 26: 1.Feeling of hunger	-0.80	—
Week 52: 1.Feeling of hunger	-0.60	—
Week 26: 2.Feeling of fullness	0.40	—
Week 52: 2.Feeling of fullness	0.35	—
Week 26: 3.Desire to eat sweet foods	-0.35	—
Week 52: 3.Desire to eat sweet foods	-0.36	—
Week 26: 4.Desire to eat savoury foods	-0.82	—
Week 52: 4.Desire to eat savoury foods	-0.82	—
Week 26: 5.Feeling of happiness	0.00	—
Week 52: 5.Feeling of happiness	0.13	—
Week 26: 6.Feeling of anxiousness	-0.21	—
Week 52: 6.Feeling of anxiousness	-0.19	—
Week 26: 7.Feeling of alertness	0.01	—
Week 52: 7.Feeling of alertness	0.07	—
Week 26: 8.Feeling of contentment	0.08	—
Week 52: 8.Feeling of contentment	0.23	—
Week 26: 9.Food cravings during 7 days	-0.43	—
Week 52: 9.Food cravings during 7 days	-0.42	—
Week 26: 10.Strength of food cravings	-0.27	—
Week 52: 10.Strength of food cravings	-0.32	—
Week 26: 11.Difficulty to resist food cravings	-0.47	—
Week 52: 11.Difficulty to resist food cravings	-0.33	—
Week 26: 12.Eating in response to food cravings	-0.19	—
Week 52: 12.Eating in response to food cravings	-0.17	—
Week 26: 13.Cravings for chocolate	-0.10	—
Week 52: 13.Cravings for chocolate	0.08	—
Week 26: 14.Cravings for other sweet foods	-0.39	—
Week 52: 14.Cravings for other sweet foods	-0.33	—
Week 26: 15.Cravings for fruit or fruit juice	-0.15	—
Week 52: 15.Cravings for fruit or fruit juice	-0.22	—
Week 26: 16.Cravings for dairy foods	-0.48	—
Week 52: 16.Cravings for dairy foods	-0.42	—
Week 26: 17.Cravings for starchy foods	-0.81	—
Week 52: 17.Cravings for starchy foods	-0.78	—
Week 26: 18.Cravings for savoury foods	-0.61	—
Week 52: 18.Cravings for savoury foods	-0.60	—
Week 26: 19.Difficulty to control eating general	-0.90	—
Week 52: 19.Difficulty to control eating general	-0.97	—
Empagliflozin 25 mgWeek 26: Craving control	0.21	—
Week 52: Craving control	0.18	—
Week 26: Positive Mood	0.19	—
Week 52: Positive Mood	0.17	—
Week 26: Craving for Savoury	-0.54	—
Week 52: Craving for Savoury	-0.44	—
Week 26: Craving for Sweet	-0.21	—
Week 52: Craving for Sweet	-0.17	—
Week 26: 1.Feeling of hunger	-0.09	—
Week 52: 1.Feeling of hunger	0.07	—
Week 26: 2.Feeling of fullness	0.29	—
Week 52: 2.Feeling of fullness	0.06	—
Week 26: 3.Desire to eat sweet foods	-0.22	—
Week 52: 3.Desire to eat sweet foods	-0.18	—
Week 26: 4.Desire to eat savoury foods	-0.56	—
Week 52: 4.Desire to eat savoury foods	-0.57	—
Week 26: 5.Feeling of happiness	0.21	—
Week 52: 5.Feeling of happiness	0.21	—
Week 26: 6.Feeling of anxiousness	-0.31	—
Week 52: 6.Feeling of anxiousness	-0.21	—
Week 26: 7.Feeling of alertness	0.02	—
Week 52: 7.Feeling of alertness	0.08	—
Week 26: 8.Feeling of contentment	0.22	—
Week 52: 8.Feeling of contentment	0.17	—
Week 26: 9.Food cravings during 7 days	-0.03	—
Week 52: 9.Food cravings during 7 days	-0.17	—
Week 26: 10.Strength of food cravings	-0.18	—
Week 52: 10.Strength of food cravings	-0.14	—
Week 26: 11.Difficulty to resist food cravings	-0.35	—
Week 52: 11.Difficulty to resist food cravings	-0.30	—
Week 26: 12.Eating in response to food cravings	-0.12	—
Week 52: 12.Eating in response to food cravings	-0.01	—
Week 26: 13.Cravings for chocolate	-0.26	—
Week 52: 13.Cravings for chocolate	-0.12	—
Week 26: 14.Cravings for other sweet foods	-0.36	—
Week 52: 14.Cravings for other sweet foods	-0.24	—
Week 26: 15.Cravings for fruit or fruit juice	0.01	—
Week 52: 15.Cravings for fruit or fruit juice	-0.15	—
Week 26: 16.Cravings for dairy foods	-0.43	—
Week 52: 16.Cravings for dairy foods	-0.16	—
Week 26: 17.Cravings for starchy foods	-0.59	—
Week 52: 17.Cravings for starchy foods	-0.51	—
Week 26: 18.Cravings for savoury foods	-0.56	—
Week 52: 18.Cravings for savoury foods	-0.50	—
Week 26: 19.Difficulty to control eating general	-0.36	—
Week 52: 19.Difficulty to control eating general	-0.27	—

Secondary/protocol endpoint

Time frame:Week 0, week 26, week 52

SF-36 total

change from baseline, improvement

Secondary/protocol endpoint

Change in CoEQ: Scores From the 4 Domains and the 19 Items

Time frame:Week 0, week 26, week 52

change from baseline, improvement

Safety / tolerability / PK

28 endpoints

Secondary/registry result

Number of Treatment-emergent Adverse Events (TEAE)

Time frame:Weeks 0-57

Treatment-emergent AEs (any)

event count, event

Posted result

Group	Value (number), Events	95% CI
Oral Semaglutide 14 mg	1022	—
Empagliflozin 25 mg	948	—

Secondary/registry result

Change in Amylase (Ratio to Baseline)

Time frame:Week 0, week 26, week 52

ratio, descriptive

Posted result

Group	Value (geometric_mean), Ratio of amylase	95% CI
Oral Semaglutide 14 mgWeek 26	1.15	—
Week 52	1.13	—
Empagliflozin 25 mgWeek 26	1.10	—
Week 52	1.11	—

Secondary/registry result

Change in Lipase (Ratio to Baseline)

Time frame:Week 0, week 26, week 52

ratio, descriptive

Posted result

Group	Value (geometric_mean), Ratio of lipase	95% CI
Oral Semaglutide 14 mgWeek 26	1.37	—
Week 52	1.27	—
Empagliflozin 25 mgWeek 26	1.10	—
Week 52	1.07	—

Secondary/registry result

Change in ECG

Time frame:Week 0, week 26, week 52

categorical status, descriptive

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mgNormal (week 0) to normal (week 26)	207	—
Normal (week 0) to abnormal NCS (week 26)	30	—
Normal (week 0) to abnormal CS (week 26)	1	—
Abnormal NCS (week 0) to normal (week 26)	50	—
Abnormal NCS (week 0) to abnormal NCS (week 26)	97	—
Abnormal NCS (week 0) to abnormal CS (week 26)	0	—
Abnormal CS (week 0) to normal (week 26)	1	—
Abnormal CS (week 0) CS to abnormal NCS (week 26)	2	—
Abnormal CS (week 0) to abnormal CS (week 26)	1	—
Normal (week 0) to normal (week 52)	196	—
Normal (week 0) to abnormal NCS (week 52)	39	—
Normal (week 0) to abnormal CS (week 52)	0	—
Abnormal (week 0) NCS to normal (week 52)	46	—
Abnormal (week 0) NCS to abnormal NCS (week 52)	98	—
Abnormal (week 0) NCS to abnormal CS (week 52)	1	—
Abnormal CS (week 0) to normal (week 52)	1	—
Abnormal CS (week 0) to abnormal NCS (week 52)	2	—
Abnormal CS (week 0) to abnormal CS (week 52)	1	—
Empagliflozin 25 mgNormal (week 0) to normal (week 26)	203	—
Normal (week 0) to abnormal NCS (week 26)	37	—
Normal (week 0) to abnormal CS (week 26)	2	—
Abnormal NCS (week 0) to normal (week 26)	41	—
Abnormal NCS (week 0) to abnormal NCS (week 26)	110	—
Abnormal NCS (week 0) to abnormal CS (week 26)	0	—
Abnormal CS (week 0) to normal (week 26)	0	—
Abnormal CS (week 0) CS to abnormal NCS (week 26)	0	—
Abnormal CS (week 0) to abnormal CS (week 26)	1	—
Normal (week 0) to normal (week 52)	194	—
Normal (week 0) to abnormal NCS (week 52)	39	—
Normal (week 0) to abnormal CS (week 52)	2	—
Abnormal (week 0) NCS to normal (week 52)	45	—
Abnormal (week 0) NCS to abnormal NCS (week 52)	97	—
Abnormal (week 0) NCS to abnormal CS (week 52)	2	—
Abnormal CS (week 0) to normal (week 52)	0	—
Abnormal CS (week 0) to abnormal NCS (week 52)	0	—
Abnormal CS (week 0) to abnormal CS (week 52)	1	—

Secondary/registry result

Change in Physical Examination

Time frame:Week -2, week 52

descriptive

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mgCardiovascular system (week -2)	381	—
Cardiovascular system (week -2)	24	—
Cardiovascular system (week -2)	5	—
Cardiovascular system (week 52)	360	—
Cardiovascular system (week 52)	21	—
Cardiovascular system (week 52)	4	—
Nervous system (week -2)	390	—
Nervous system (week -2)	20	—
Nervous system (week -2)	0	—
Nervous system (week 52)	371	—
Nervous system (week 52)	13	—
Nervous system (week 52)	1	—
Gastrointestinal system (week -2)	387	—
Gastrointestinal system (week -2)	23	—
Gastrointestinal system (week -2)	0	—
Gastrointestinal system (week 52)	366	—
Gastrointestinal system (week 52)	18	—
Gastrointestinal system (week 52)	1	—
General appearance (week -2)	354	—
General appearance (week -2)	47	—
General appearance (week -2)	9	—
General appearance (week 52)	345	—
General appearance (week 52)	36	—
General appearance (week 52)	4	—
Head, throat, neck (week -2)	389	—
Head, throat, neck (week -2)	18	—
Head, throat, neck (week -2)	3	—
Head, throat, neck (week 52)	376	—
Head, throat, neck (week 52)	8	—
Head, throat, neck (week 52)	1	—
Lymph node palpation (week -2)	409	—
Lymph node palpation (week -2)	1	—
Lymph node palpation (week -2)	0	—
Lymph node palpation (week 52)	385	—
Lymph node palpation (week 52)	0	—
Lymph node palpation (week 52)	0	—
Musculoskeletal system (week -2)	389	—
Musculoskeletal system (week -2)	18	—
Musculoskeletal system (week -2)	3	—
Musculoskeletal system (week 52)	370	—
Musculoskeletal system (week 52)	15	—
Musculoskeletal system (week 52)	0	—
Respiratory system (week -2)	400	—
Respiratory system (week -2)	9	—
Respiratory system (week -2)	1	—
Respiratory system (week 52)	375	—
Respiratory system (week 52)	8	—
Respiratory system (week 52)	2	—
Skin (week -2)	357	—
Skin (week -2)	50	—
Skin (week -2)	3	—
Skin (week 52)	346	—
Skin (week 52)	37	—
Skin (week 52)	2	—
Thyroid gland (week -2)	399	—
Thyroid gland (week -2)	11	—
Thyroid gland (week -2)	0	—
Thyroid gland (week 52)	376	—
Thyroid gland (week 52)	9	—
Thyroid gland (week 52)	0	—
Empagliflozin 25 mgCardiovascular system (week -2)	372	—
Cardiovascular system (week -2)	34	—
Cardiovascular system (week -2)	3	—
Cardiovascular system (week 52)	351	—
Cardiovascular system (week 52)	29	—
Cardiovascular system (week 52)	2	—
Nervous system (week -2)	376	—
Nervous system (week -2)	30	—
Nervous system (week -2)	3	—
Nervous system (week 52)	365	—
Nervous system (week 52)	17	—
Nervous system (week 52)	1	—
Gastrointestinal system (week -2)	384	—
Gastrointestinal system (week -2)	24	—
Gastrointestinal system (week -2)	1	—
Gastrointestinal system (week 52)	360	—
Gastrointestinal system (week 52)	22	—
Gastrointestinal system (week 52)	0	—
General appearance (week -2)	354	—
General appearance (week -2)	49	—
General appearance (week -2)	6	—
General appearance (week 52)	338	—
General appearance (week 52)	41	—
General appearance (week 52)	4	—
Head, throat, neck (week -2)	382	—
Head, throat, neck (week -2)	26	—
Head, throat, neck (week -2)	1	—
Head, throat, neck (week 52)	362	—
Head, throat, neck (week 52)	19	—
Head, throat, neck (week 52)	2	—
Lymph node palpation (week -2)	409	—
Lymph node palpation (week -2)	0	—
Lymph node palpation (week -2)	0	—
Lymph node palpation (week 52)	381	—
Lymph node palpation (week 52)	0	—
Lymph node palpation (week 52)	0	—
Musculoskeletal system (week -2)	384	—
Musculoskeletal system (week -2)	25	—
Musculoskeletal system (week -2)	0	—
Musculoskeletal system (week 52)	363	—
Musculoskeletal system (week 52)	20	—
Musculoskeletal system (week 52)	0	—
Respiratory system (week -2)	403	—
Respiratory system (week -2)	6	—
Respiratory system (week -2)	0	—
Respiratory system (week 52)	378	—
Respiratory system (week 52)	4	—
Respiratory system (week 52)	0	—
Skin (week -2)	354	—
Skin (week -2)	53	—
Skin (week -2)	2	—
Skin (week 52)	340	—
Skin (week 52)	42	—
Skin (week 52)	1	—
Thyroid gland (week -2)	389	—
Thyroid gland (week -2)	18	—
Thyroid gland (week -2)	2	—
Thyroid gland (week 52)	367	—
Thyroid gland (week 52)	16	—
Thyroid gland (week 52)	0	—

Secondary/registry result

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

Time frame:Weeks 0-57

Immunogenicity (ADA)

threshold achievement, event

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mg	2	—

Secondary/registry result

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

Time frame:Weeks 0-57

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 0-57

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 Neutralising Antibodies Cross Reacting With Native GLP-1 (Yes/no)

Time frame:Weeks 0-57

Immunogenicity (ADA)

categorical status, 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 0-57

Immunogenicity (ADA)

descriptive

Posted result

Group	Value (mean), %B/T	95% CI
Oral Semaglutide 14 mgWeek 4	2.75	—
Week 8	2.17	—

Secondary/registry result

Number of Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes

Time frame:Weeks 0-57

Documented hypoglycemia

event count, event

componentsSevere hypoglycemia, Documented hypoglycemia

Posted result

Group	Value (number), Episodes	95% CI
Oral Semaglutide 14 mg	10	—
Empagliflozin 25 mg	9	—

Secondary/registry result

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

Time frame:Weeks 0-57

Documented hypoglycemia

threshold achievement, event

componentsSevere hypoglycemia, Documented hypoglycemia

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mg	7	—
Empagliflozin 25 mg	8	—

Secondary/registry result

Semaglutide Plasma Concentrations for Population PK Analyses

Time frame:Weeks 0-52

Plasma concentration (steady state)

concentration, descriptive

Posted result

Group	Value (geometric_mean), Nanomoles per liter (nmol/L)	95% CI
Oral Semaglutide 14 mgWeek 4	3.5	—
Week 26	15.6	—
Week 52	14.4	—

Secondary/registry result

SNAC Plasma Concentrations

Time frame:Weeks 0-52

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	559	—
Week 4: 40 minutes post-dose	375	—
Week 26: 25 minutes post-dose	474	—
Week 26: 40 minutes post-dose	373	—
Week 52: 25 minutes post-dose	448	—
Week 52: 40 minutes post-dose	301	—

Secondary/protocol endpoint

Number of Treatment-emergent Adverse Events (TEAE)

Time frame:Weeks 0-57

Treatment-emergent AEs (any)

event count, event

Secondary/protocol endpoint

Change in Amylase (Ratio to Baseline)

Time frame:Week 0, week 26, week 52

ratio, descriptive

Secondary/protocol endpoint

Change in Lipase (Ratio to Baseline)

Time frame:Week 0, week 26, week 52

ratio, descriptive

Secondary/protocol endpoint

Change in ECG

Time frame:Week 0, week 26, week 52

categorical status, descriptive

Secondary/protocol endpoint

Change in Physical Examination

Time frame:Week -2, week 52

descriptive

Secondary/protocol endpoint

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

Time frame:Weeks 0-57

Immunogenicity (ADA)

categorical status, event

Secondary/protocol endpoint

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

Time frame:Weeks 0-57

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 0-57

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 0-57

Immunogenicity (ADA)

categorical status, event

Secondary/protocol endpoint

Anti-semaglutide Binding Antibody Levels

Time frame:Weeks 0-57

Immunogenicity (ADA)

descriptive

Secondary/protocol endpoint

Number of Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes

Time frame:Weeks 0-57

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 0-57

Documented hypoglycemia

threshold achievement, event

componentsSevere hypoglycemia, Documented hypoglycemia

Secondary/protocol endpoint

Semaglutide Plasma Concentrations for Population PK Analyses

Time frame:Weeks 0-52

Plasma concentration (steady state)

concentration, descriptive

Secondary/protocol endpoint

SNAC Plasma Concentrations

Time frame:Weeks 0-52

Plasma concentration (steady state)

concentration, descriptive

Other clinical outcomes

2 endpoints

Secondary/registry result

Change in Eye Examination

Time frame:Week -2, week 52

categorical status, descriptive

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 14 mgLeft eye (week -2)	295	—
Left eye (week -2)	107	—
Left eye (week -2)	7	—
Left eye (week 52)	264	—
Left eye (week 52)	103	—
Left eye (week 52)	8	—
Right eye (week -2)	294	—
Right eye (week -2)	109	—
Right eye (week -2)	6	—
Right eye (week 52)	267	—
Right eye (week 52)	96	—
Right eye (week 52)	11	—
Empagliflozin 25 mgLeft eye (week -2)	295	—
Left eye (week -2)	102	—
Left eye (week -2)	10	—
Left eye (week 52)	269	—
Left eye (week 52)	93	—
Left eye (week 52)	10	—
Right eye (week -2)	293	—
Right eye (week -2)	107	—
Right eye (week -2)	9	—
Right eye (week 52)	269	—
Right eye (week 52)	93	—
Right eye (week 52)	11	—

Secondary/protocol endpoint

Change in Eye Examination

Time frame:Week -2, week 52

categorical status, descriptive

Other (unclassified)

3 endpoints

Secondary/protocol endpoint/low confidence

Change in Fasting Pro-insulin (Ratio to Baseline)

Time frame:Week 0, week 26 and week 52

ratio, improvement

Secondary/protocol endpoint/low confidence

Change in Fasting Glucagon (Ratio to Baseline)

Time frame:Week 0, week 26 and week 52

ratio, improvement

Secondary/protocol endpoint/low confidence

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

Time frame:Week 26 and week 52

threshold achievement, improvement

componentsHbA1c, change, Body weight, % change

Publications (9)

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

Cost-Effectiveness of Semaglutide vs. Empagliflozin, Canagliflozin, and Sitagliptin for Treatment of Patients with Type 2 Diabetes in Denmark: A Decision-Analytic Modelling Study.
PharmacoEconomics - open2023 Jul (month)PMID37178435doi:10.1007/s41669-023-00416-zvia 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
Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme.
Diabetes, obesity & metabolism2022 Jul (month)PMID35373893doi:10.1111/dom.14710via CT.gov reference
Long-Term Cost Effectiveness of Oral Semaglutide Versus Empagliflozin and Sitagliptin for the Treatment of Type 2 Diabetes in the Swedish Setting.
PharmacoEconomics - open2022 May (month)PMID35064550doi:10.1007/s41669-021-00317-zvia CT.gov reference + pubmed nct search
Efficacy of Once-Weekly Semaglutide vs Empagliflozin Added to Metformin in Type 2 Diabetes: Patient-Level Meta-analysis.
The Journal of clinical endocrinology and metabolism2020 Dec 1PMID32827435doi:10.1210/clinem/dgaa577via 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 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
Oral Semaglutide Versus Empagliflozin in Patients With Type 2 Diabetes Uncontrolled on Metformin: The PIONEER 2 Trial.
Diabetes care2019 Dec (month)PMID31530666doi:10.2337/dc19-0883via 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.