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

NCT05035082 | Completed Phase 4 FDA Drug

• 2 other identifiers: NN9924-4558U1111-1253-2577
• Study Type: interventional
• Target: 1,020
• Locations: 1 country
• Sites: 25

Brief Summary

This study is comparing the medicine RYBELSUS® to other medicines in people with type 2 diabetes who need extra treatment. All medicines used in this study are tablets which lower blood sugar in people with type 2 diabetes. The purpose of the study is to see how well RYBELSUS® is at lowering blood sugar compared to other tablets when used in addition to metformin. Participants doctor will give participants either RYBELSUS® or any other blood sugar lowering tablets - which treatment participants get is decided by chance. The doctor treating participants diabetes will give participants a prescription for the medicine and tell how to take it. The study will last for about 1 year. Participants will have 2 planned visits with their doctor which are part of the usual routine diabetes management: the first visit is when participants are included in the study, the second visit is a 1-year follow-up visit. In addition, the study personnel will contact participants up to 3 times during this period and to follow-up on information from participant doctors visits. Participant will be asked to respond 3 times to 4 questionnaires via their personal smartphone or tablet or paper if participant do not have access to one during the study. All clinic visits are part of the usual routine diabetes management and are covered by participants health insurance plan. The study team will collect information from these visits recorded in the medical chart. Women cannot take part if pregnant, breast-feeding or plan to become pregnant during the study period.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• Change in Glycosylated hemoglobin A1c (HbA1c)

  percentage-points

  From randomization to year 1

Secondary Outcomes (10)

• Patient achieving HbA1c below 7.0% (Yes /No)

  Year 1

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

  Year 1

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

  From randomization to year 1

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

  From randomization to year 1

• 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)

  Year 1

Study Arms (2)

oral semaglutide

EXPERIMENTAL

All participants are given tablets used in addition to metformin.

Drug: semaglutide

other oral glucose lowering medication

ACTIVE COMPARATOR

All participants are given tablets used in addition to metformin.

Drug: oral glucose-lowering medications (commercially available)

Interventions

semaglutide DRUG

Oral administration The doctor will give a prescription for the medicine and tell how to take it.

oral semaglutide

oral glucose-lowering medications (commercially available) DRUG

Oral administration The doctor will give a prescription for the medicine and tell how to take it.

other oral glucose lowering medication

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novo Nordisk A/S: lead

Study Sites (25)

Stewart Medical Group

Alhambra, California, 91801, United States

Location

FDRC

Costa Mesa, California, 92627, United States

Location

Scripps Whittier Diabetes Inst

La Jolla, California, 92037, United States

Location

Raincross Medical Group

Riverside, California, 92506, United States

Location

Reyes Clinical Research, Inc

Miami, Florida, 33175, United States

Location

DC Research Works

Marietta, Georgia, 30060, United States

Location

Urban Family Practice Assoc

Marietta, Georgia, 30067, United States

Location

Macoupin Research Group

Gillespie, Illinois, 62033, United States

Location

UnityPoint Health-Diabetes Care Center

Peoria, Illinois, 61603, United States

Location

Endeavor Health

Skokie, Illinois, 60077, United States

Location

Kernodle Clin Dpt-Pvt Diagnost

Burlington, North Carolina, 27215, United States

Location

OnSite Clinical Solutions, LLC_Charlotte

Charlotte, North Carolina, 28277, United States

Location

WakeMed Garner Hlthplx

Garner, North Carolina, 27529, United States

Location

Clinical Research of Gastonia

Gastonia, North Carolina, 28054, United States

Location

Valley Weight Loss Clinic

Fargo, North Dakota, 58104, United States

Location

Diab & Endo Assoc of Stark Co

Canton, Ohio, 44718, United States

Location

Central Ohio Clinical Research LLC

Columbus, Ohio, 43213, United States

Location

Jefferson Endocrinology Assocs

Philadelphia, Pennsylvania, 19107-6810, United States

Location

Tristar Clin Investigations, PC

Philadelphia, Pennsylvania, 19114, United States

Location

Preferred Primary Care Physicians_Pittsburgh

Pittsburgh, Pennsylvania, 15236, United States

Location

AnMed Health IMA

Anderson, South Carolina, 29621, United States

Location

Baylor Scott & White Res Inst

Dallas, Texas, 75246, United States

Location

Hill Country Medical Associates

New Braunfels, Texas, 78130, United States

Location

DCT-Stone Oak

San Antonio, Texas, 78258, United States

Location

Chrysalis Clinical Research

St. George, Utah, 84790, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Clinical Transparency (dept. 1452)

  Novo Nordisk A/S

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2021
• First Posted: September 5, 2021
• Study Start: September 1, 2021
• Primary Completion: June 18, 2025
• Study Completion: June 18, 2025
• Last Updated: November 25, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

US (25)