SUSTAIN™ 4

CompletedPhase 3Results posted

Efficacy and Safety of Semaglutide Once Weekly Versus Insulin Glargine Once Daily as add-on to Metformin With or Without Sulphonylurea in Insulin-naïve Subjects With Type 2 Diabetes

Efficacy and Safety of Semaglutide Once Weekly Versus Insulin Glargine Once Daily as Add on to Metformin With or Without Sulphonylurea in Insulin-naïve Subjects With Type 2 Diabetes

Lead sponsor

Novo Nordisk A/S

Asset

Semaglutide

Subcutaneous · GLP-1 agonist

Listed sites

231

Recruiting sites

—

Enrollment

1,089

actual

Study population

Type 2 diabetes

Key I/E criterion

•HbA1c 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 IDNCT02128932

Org study IDNN9535-3625

Secondary ID2013-004392-12

Secondary IDNL47781.018.14National Registry in The Netherlands

Secondary IDU1111-1146-0211WHO

Timeline

Milestones

Study first posted2014-05-01estimated

Study start2014-08-04actual

Primary completion2015-09-03actual

Study completion2015-09-03actual

Results first posted2018-03-08actual

Last update posted2019-06-13actual

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

•Male or female, 18 years or older at the time of signing informed consent

•Insulin-naïve subjects diagnosed with type 2 diabetes and on stable diabetes treatment with metformin or metformin and SU (metformin 1500 mg or higher or maximum tolerated dose and SU half of maximum allowed dose according to national label or higher) for at least 90 days before screening. Stable is defined as unchanged medication and unchanged dose

•HbA1c 7.0 - 10.0% (53 - 86 mmol/mol) both inclusive

Exclusion criteria

•Female who is pregnant, breast-feeding or intends to become pregnant or of childbearing potential not using adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice) throughout the trial including the 5 week follow-up period

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

•Treatment with any glucose lowering agent(s) other than stated in the inclusion criteria in a period of 90 days before screening. An exception is short-term treatment (7 days or less in total) with insulin in connection with intercurrent illness

•History of chronic or idiopathic acute pancreatitis

•Screening calcitonin value greater than or equal to 50 ng/L

•Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome 2

•Severe renal impairment defined as estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m^2 per modification of diet in renal disease (MDRD) formula (4 variable version)

•Acute coronary or cerebrovascular event within 90 days before randomisation

•Heart failure, New York Heart Association Class IV

•Known proliferative retinopathy or maculopathy requiring acute treatment according to the opinion of the investigator

•Diagnosis of malignant neoplasm in the previous 5 years (except basal cell skin cancer or squamous cell skin cancer)

•Mental inability, unwillingness or language barrier precluding adequate understanding of or compliance with study procedures

Endpoints (16)

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

Cardiometabolic biomarkers

Patient-reported / QoL

Weight & body composition

2 endpoints

Secondary/registry result

Change in Body Weight From Baseline

Time frame:Week 0, week 30

Body weight, absolute change (kg)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Kg	95% CI
Semaglutide 0.5mg/Week	-3.47	—
Semaglutide 1.0 mg/Week	-5.17	—
Insulin Glargine	1.15	—

Secondary/protocol endpoint

Change in Body Weight From Baseline

Time frame:Week 0, week 30

Body weight, absolute change (kg)

change from baseline, improvement

Glycemic / diabetes

6 endpoints

Primary/registry result

Change in HbA1c From Baseline

Time frame:Week 0, week 30

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

Group	Value (least_squares_mean), percentage	95% CI
Semaglutide 0.5mg/Week	-1.21	—
Semaglutide 1.0 mg/Week	-1.64	—
Insulin Glargine	-0.83	—

Treatment difference-0.8195% CI-0.96 – -0.67p<0.0001Mixed Models Analysis

The post baseline responses were analysed using a mixed model for repeated measurements with treatment , country and stratum as fixed factors and baseline value as covariate, all nested within visit.

Treatment difference-0.3895% CI-0.52 – -0.24p<0.0001Mixed Models Analysis

The post baseline responses were analysed using a mixed model for repeated meausrements with treatment, country and stratum value as covariate, all nested within visit.

Primary/protocol endpoint

Change in HbA1c From Baseline

Time frame:Week 0, week 30

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/registry result

Change in Fasting Plasma Glucose From Baseline

Time frame:Week 0, week 30

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

Group	Value (least_squares_mean), mg/dL	95% CI
Semaglutide 0.5mg/Week	-36.74	—
Semaglutide 1.0 mg/Week	-49.21	—
Insulin Glargine	-38.18	—

Secondary/registry result

Subjects Who Achieve HbA1c ≤6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists (AACE)

Time frame:After 30 weeks treatment

HbA1c <6.5% achievement

threshold achievement, improvement

LOINC 4548-4

Posted result

Group	Value (number), Count of participants	95% CI
Semaglutide 0.5mg/WeekYes	135	—
No	227	—
Semaglutide 1.0 mg/WeekYes	195	—
No	165	—
Insulin GlargineYes	63	—
No	297	—

Secondary/protocol endpoint

Change in Fasting Plasma Glucose From Baseline

Time frame:Week 0, week 30

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Subjects Who Achieve HbA1c ≤6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists (AACE)

Time frame:After 30 weeks treatment

HbA1c <6.5% achievement

threshold achievement, improvement

LOINC 4548-4

Cardiometabolic biomarkers

4 endpoints

Secondary/registry result

Change in Diastolic Blood Pressure.

Time frame:Week 0, week 30

Diastolic BP, change

change from baseline, improvement

LOINC 8462-4

Posted result

Group	Value (least_squares_mean), mmHg	95% CI
Semaglutide 0.5mg/Week	-1.38	—
Semaglutide 1.0 mg/Week	-0.98	—
Insulin Glargine	-1.44	—

Secondary/registry result

Change in Systolic Blood Pressure.

Time frame:Week 0, week 30

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Posted result

Group	Value (least_squares_mean), mmHg	95% CI
Semaglutide 0.5mg/Week	-4.65	—
Semaglutide 1.0 mg/Week	-5.17	—
Insulin Glargine	-1.68	—

Secondary/protocol endpoint

Change in Diastolic Blood Pressure.

Time frame:Week 0, week 30

Diastolic BP, change

change from baseline, improvement

LOINC 8462-4

Secondary/protocol endpoint

Change in Systolic Blood Pressure.

Time frame:Week 0, week 30

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Patient-reported / QoL

4 endpoints

Secondary/registry result

Change in Patient Reported Outcome (PRO) Questionnaire, Questionnaire SF-36v2™

Time frame:Week 0, week 30

SF-36 total

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), T-scores	95% CI
Semaglutide 0.5mg/WeekBodily pain	0.95	—
General Health	1.95	—
Mental Component summary, MCS	1.23	—
Mental Health	1.69	—
Physical Component summary, PCS	1.18	—
Physical Functioning	1.64	—
Role-emotional	0.88	—
Role-physical	0.90	—
Social functioning	1.13	—
Vitality	1.71	—
Semaglutide 1.0 mg/WeekBodily pain	1.76	—
General Health	2.78	—
Mental Component summary, MCS	1.33	—
Mental Health	1.17	—
Physical Component summary, PCS	2.09	—
Physical Functioning	1.49	—
Role-emotional	1.73	—
Role-physical	1.97	—
Social functioning	1.04	—
Vitality	2.09	—
Insulin GlargineBodily pain	0.90	—
General Health	1.63	—
Mental Component summary, MCS	0.25	—
Mental Health	0.54	—
Physical Component summary, PCS	1.18	—
Physical Functioning	0.69	—
Role-emotional	0.06	—
Role-physical	0.78	—
Social functioning	0.36	—
Vitality	0.95	—

Secondary/registry result

Change in Patient Reported Outcome Questionnaires. (PROs), Diabetes Treatment Satisfaction Questionnaire (DTSQs)

Time frame:Week 0, week 30

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Score on a scale	95% CI
Semaglutide 0.5mg/Week	4.86	—
Semaglutide 1.0 mg/Week	5.37	—
Insulin Glargine	3.99	—

Secondary/protocol endpoint

Change in Patient Reported Outcome (PRO) Questionnaire, Questionnaire SF-36v2™

Time frame:Week 0, week 30

SF-36 total

change from baseline, improvement

Secondary/protocol endpoint

Change in Patient Reported Outcome Questionnaires. (PROs), Diabetes Treatment Satisfaction Questionnaire (DTSQs)

Time frame:Week 0, week 30

change from baseline, improvement

Publications (12)

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

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
Once-Weekly Semaglutide Reduces HbA(1c) and Body Weight in Patients with Type 2 Diabetes Regardless of Background Common OAD: a Subgroup Analysis from SUSTAIN 2-4 and 10.
Diabetes therapy : research, treatment and education of diabetes and related disorders2020 May (month)PMID32193837doi:10.1007/s13300-020-00796-zvia 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 Semaglutide for Type 2 Diabetes by Race and Ethnicity: A Post Hoc Analysis of the SUSTAIN Trials.
The Journal of clinical endocrinology and metabolism2020 Feb 1PMID31769496doi:10.1210/clinem/dgz072via clinicaltrials gov reference derived + pubmed nct search
Improved treatment satisfaction in patients with type 2 diabetes treated with once-weekly semaglutide in the SUSTAIN trials.
Diabetes, obesity & metabolism2019 Oct (month)PMID31215727doi:10.1111/dom.13816via clinicaltrials gov reference derived + pubmed nct search
Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: Insights from the SUSTAIN 1-7 trials.
Diabetes & metabolism2019 Oct (month)PMID30615985doi:10.1016/j.diabet.2018.12.001via CT.gov reference
GREATER COMBINED REDUCTIONS IN HbA(1C) ≥1.0% AND WEIGHT ≥5.0% WITH SEMAGLUTIDE VERSUS COMPARATORS IN TYPE 2 DIABETES.
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists2019 Jun (month)PMID30865526doi:10.4158/EP-2018-0444via CT.gov background
Achieving glycaemic control without weight gain, hypoglycaemia, or gastrointestinal adverse events in type 2 diabetes in the SUSTAIN clinical trial programme.
Diabetes, obesity & metabolism2018 Oct (month)PMID29862621doi:10.1111/dom.13396via CT.gov reference
Semaglutide induces weight loss in subjects with type 2 diabetes regardless of baseline BMI or gastrointestinal adverse events in the SUSTAIN 1 to 5 trials.
Diabetes, obesity & metabolism2018 Sep (month)PMID29766634doi:10.1111/dom.13353via CT.gov reference
Semaglutide as a therapeutic option for elderly patients with type 2 diabetes: Pooled analysis of the SUSTAIN 1-5 trials.
Diabetes, obesity & metabolism2018 Sep (month)PMID29687620doi:10.1111/dom.13331via CT.gov reference
Effects of semaglutide on beta cell function and glycaemic control in participants with type 2 diabetes: a randomised, double-blind, placebo-controlled trial.
Diabetologia2017 Aug (month)PMID28526920doi:10.1007/s00125-017-4289-0via CT.gov reference
Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial.
The lancet. Diabetes & endocrinology2017 May (month)PMID28344112doi:10.1016/S2213-8587(17)30085-2via 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.