REALYSE

CompletedPhase 4

A Research Study Comparing RYBELSUS® to Other Blood Sugar Lowering Tablets in People Living in America With Type 2 Diabetes (REALYSE)

REALYSE - Comparative Effectiveness of Once-daily Oral Semaglutide Versus Any Other Oral Glucose-lowering Medication in a Real-world Adult Population With Type 2 Diabetes on Metformin Monotherapy in US Based Health Care Systems - a Pragmatic Randomized Trial

Lead sponsor

Novo Nordisk A/S

Asset

Semaglutide

Oral · GLP-1 agonist

Listed sites

Recruiting sites

—

Enrollment

1,020

actual

Study population

Type 2 diabetes

Key I/E criterion

•HbA1c ≥7%

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 IDNCT05035082

Org study IDNN9924-4558

Secondary IDU1111-1253-2577World Health Organization (WHO)

Timeline

Milestones

Study start2021-09-01actual

Study first posted2021-09-05actual

Primary completion2025-06-18actual

Study completion2025-06-18actual

Last update posted2025-11-25actual

Assets

Investigational agents

Semaglutide

Study populations

Who this study enrolls

Type 2 diabetes

Eligibility

Who can enroll

Minimum age18 Years

SexAll

Healthy volunteersNot accepted

Eligibility criteria

Key inclusion criteria

•Treatment with metformin as monotherapy prior to eligibility assessment that has failed to result in adequate glycemic control at the discretion of the investigator or treatment provider. However, prior short-term treatment with an oral glucose lowering agent or insulin for up to 14 consecutive days in addition to metformin is allowed if discontinued prior to screening.

•Current member of a health plan which includes pharmacy benefits.

•HbA1c greater than or equal to 7% within last 90 days prior to the day of screening or to be taken before randomization.

•Further intensification with an additional glucose-lowering oral agent including oral semaglutide is indicated according to approved prescribing information to achieve glycemic target at the discretion of the treatment provider.

Key exclusion criteria:

•Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using contraception.

•Any disorder which in the investigator's or treatment provider's opinion might jeopardize patient's safety.

Endpoints (11)

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

Weight & body composition

Patient-reported / QoL

Weight & body composition

3 endpoints

Secondary/protocol endpoint

Patient achieving greater than or equal to 5% reduction in body weight (Yes/No)

Time frame:From randomization to year 1

≥5% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

Relative change in body weight (%)

Time frame:From randomization to year 1

Body weight, % change

percent change from baseline, improvement

Secondary/protocol endpoint

Change in body weight (lbs)

Time frame:From randomization to year 1

Body weight, absolute change (kg)

change from baseline, improvement

Glycemic / diabetes

7 endpoints

Primary/protocol endpoint

Change in Glycosylated hemoglobin A1c (HbA1c)

Time frame:From randomization to year 1

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/protocol endpoint

Patient achieving HbA1c below 7.0% (Yes /No)

Time frame:Year 1

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Secondary/protocol endpoint

Patient achieving HbA1c below or equal to 6.5% (Yes/No)

Time frame:Year 1

HbA1c <6.5% achievement

threshold achievement, improvement

LOINC 4548-4

Secondary/protocol endpoint

Patient achieving HbA1c below 7.0% or at least 1.0%-point reduction in HbA1c (Yes/No)

Time frame:From randomization to year 1

HbA1c <7.0% achievement

threshold achievement, improvement

componentsHbA1c <7.0% achievement, HbA1c, change

LOINC 4548-4

Secondary/protocol endpoint

Patient achieving individualized HbA1c target per Healthcare Effectiveness Data and Information Set (HEDIS) criteria (below 8.0% if age greater than or equal to 65 years or with defined comorbidities or otherwise below 7.0%) (Yes/No)

Time frame:Year 1

threshold achievement, improvement

LOINC 4548-4

Secondary/protocol endpoint

Patient achieving HbA1c less than or equal to treatment provider defined individualized target (Yes/No)

Time frame:Year 1

threshold achievement, improvement

LOINC 4548-4

Secondary/protocol endpoint

Time to treatment intensification (add-on) or change (switch)

Time frame:From randomization to year 1

time to event, event

Patient-reported / QoL

1 endpoint

Secondary/protocol endpoint

Diabetes Treatment Satisfaction Questionnaire, change version (DTSQc), Relative treatment satisfaction total score

Time frame:Year 1

PGI, change

change from baseline, improvement

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableno registry results posted yet

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.