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

Last updated: November 24, 2025
Sponsor: Novo Nordisk A/S
Overall Status: Completed

Phase

4

Condition

Diabetes And Hypertension

Diabetes Mellitus, Type 2

Diabetes Prevention

Treatment

semaglutide

oral glucose-lowering medications (commercially available)

Clinical Study ID

NCT05035082
NN9924-4558
U1111-1253-2577
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Key inclusion criteria

  • Treatment with metformin as monotherapy prior to eligibility assessment that hasfailed to result in adequate glycemic control at the discretion of the investigatoror treatment provider. However, prior short-term treatment with an oral glucoselowering agent or insulin for up to 14 consecutive days in addition to metformin isallowed 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 screeningor to be taken before randomization.

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

Exclusion

Key exclusion criteria:

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

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

Study Design

Total Participants: 1020
Treatment Group(s): 2
Primary Treatment: semaglutide
Phase: 4
Study Start date:
September 01, 2021
Estimated Completion Date:
June 18, 2025

Connect with a study center

  • Novo Nordisk Investigational Site

    Alhambra, California 91801
    United States

    Suspended

  • Stewart Medical Group

    Alhambra, California 91801
    United States

    Site Not Available

  • FDRC

    Costa Mesa, California 92627
    United States

    Site Not Available

  • Novo Nordisk Investigational Site

    Costa Mesa, California 92627
    United States

    Active - Recruiting

  • Novo Nordisk Investigational Site

    La Jolla, California 92037
    United States

    Active - Recruiting

  • Scripps Whittier Diabetes Inst

    La Jolla, California 92037
    United States

    Site Not Available

  • Novo Nordisk Investigational Site

    Riverside, California 92506
    United States

    Active - Recruiting

  • Raincross Medical Group

    Riverside, California 92506
    United States

    Site Not Available

  • Stewart Medical Group

    Alhambra 5323060, California 5332921 91801
    United States

    Site Not Available

  • FDRC

    Costa Mesa 5339840, California 5332921 92627
    United States

    Site Not Available

  • Scripps Whittier Diabetes Inst

    La Jolla 5363943, California 5332921 92037
    United States

    Site Not Available

  • Raincross Medical Group

    Riverside 5387877, California 5332921 92506
    United States

    Site Not Available

  • Novo Nordisk Investigational Site

    Miami, Florida 33175
    United States

    Active - Recruiting

  • Reyes Clinical Research, Inc

    Miami, Florida 33175
    United States

    Site Not Available

  • Reyes Clinical Research, Inc

    Miami 4164138, Florida 4155751 33175
    United States

    Site Not Available

  • DC Research Works

    Marietta, Georgia 30060
    United States

    Site Not Available

  • Novo Nordisk Investigational Site

    Marietta, Georgia 30067
    United States

    Active - Recruiting

  • Urban Family Practice Assoc

    Marietta, Georgia 30067
    United States

    Site Not Available

  • DC Research Works

    Marietta 4207783, Georgia 4197000 30060
    United States

    Site Not Available

  • Urban Family Practice Assoc

    Marietta 4207783, Georgia 4197000 30067
    United States

    Site Not Available

  • Novo Nordisk Investigational Site

    Carlinville, Illinois 62626
    United States

    Site Not Available

  • Macoupin Research Group

    Gillespie, Illinois 62033
    United States

    Site Not Available

  • Novo Nordisk Investigational Site

    Gillespie, Illinois 62033
    United States

    Active - Recruiting

  • Novo Nordisk Investigational Site

    Peoria, Illinois 61603
    United States

    Active - Recruiting

  • UnityPoint Health-Diabetes Care Center

    Peoria, Illinois 61603
    United States

    Site Not Available

  • Endeavor Health

    Skokie, Illinois 60077
    United States

    Site Not Available

  • NorthShore Univ Hlth Sys

    Skokie, Illinois 60077
    United States

    Site Not Available

  • Novo Nordisk Investigational Site

    Skokie, Illinois 60077
    United States

    Active - Recruiting

  • Macoupin Research Group

    Gillespie 4239423, Illinois 4896861 62033
    United States

    Site Not Available

  • UnityPoint Health-Diabetes Care Center

    Peoria 4905687, Illinois 4896861 61603
    United States

    Site Not Available

  • Endeavor Health

    Skokie 4911600, Illinois 4896861 60077
    United States

    Site Not Available

  • Kernodle Clin Dpt-Pvt Diagnost

    Burlington, North Carolina 27215
    United States

    Site Not Available

  • Novo Nordisk Investigational Site

    Burlington, North Carolina 27215
    United States

    Completed

  • Novo Nordisk Investigational Site

    Charlotte, North Carolina 28277
    United States

    Active - Recruiting

  • OnSite Clinical Solutions, LLC_Charlotte

    Charlotte, North Carolina 28277
    United States

    Site Not Available

  • Novo Nordisk Investigational Site

    Garner, North Carolina 27529
    United States

    Active - Recruiting

  • WakeMed Garner Hlthplx

    Garner, North Carolina 27529
    United States

    Site Not Available

  • Clinical Research of Gastonia

    Gastonia, North Carolina 28054
    United States

    Site Not Available

  • Novo Nordisk Investigational Site

    Gastonia, North Carolina 28054
    United States

    Active - Recruiting

  • Kernodle Clin Dpt-Pvt Diagnost

    Burlington 4458228, North Carolina 4482348 27215
    United States

    Site Not Available

  • OnSite Clinical Solutions, LLC_Charlotte

    Charlotte 4460243, North Carolina 4482348 28277
    United States

    Site Not Available

  • WakeMed Garner Hlthplx

    Garner 4467657, North Carolina 4482348 27529
    United States

    Site Not Available

  • Clinical Research of Gastonia

    Gastonia 4467732, North Carolina 4482348 28054
    United States

    Site Not Available

  • Novo Nordisk Investigational Site

    Fargo, North Dakota 58104
    United States

    Active - Recruiting

  • Valley Weight Loss Clinic

    Fargo, North Dakota 58104
    United States

    Site Not Available

  • Valley Weight Loss Clinic

    Fargo 5059163, North Dakota 5690763 58104
    United States

    Site Not Available

  • Diab & Endo Assoc of Stark Co

    Canton, Ohio 44718
    United States

    Site Not Available

  • Novo Nordisk Investigational Site

    Canton, Ohio 44718
    United States

    Active - Recruiting

  • Central Ohio Clinical Research LLC

    Columbus, Ohio 43213
    United States

    Site Not Available

  • Novo Nordisk Investigational Site

    Columbus, Ohio 43213
    United States

    Active - Recruiting

  • Diab & Endo Assoc of Stark Co

    Canton 5149222, Ohio 5165418 44718
    United States

    Site Not Available

  • Central Ohio Clinical Research LLC

    Columbus 4509177, Ohio 5165418 43213
    United States

    Site Not Available

  • Jefferson Endocrinology Assocs

    Philadelphia, Pennsylvania 19107-6810
    United States

    Site Not Available

  • Novo Nordisk Investigational Site

    Philadelphia, Pennsylvania 19107-6810
    United States

    Active - Recruiting

  • Tristar Clin Investigations, PC

    Philadelphia, Pennsylvania 19114
    United States

    Site Not Available

  • Novo Nordisk Investigational Site

    Pittsburgh, Pennsylvania 15236
    United States

    Active - Recruiting

  • Preferred Primary Care Physicians_Pittsburgh

    Pittsburgh, Pennsylvania 15236
    United States

    Site Not Available

  • Jefferson Endocrinology Assocs

    Philadelphia 4560349, Pennsylvania 6254927 19107-6810
    United States

    Site Not Available

  • Tristar Clin Investigations, PC

    Philadelphia 4560349, Pennsylvania 6254927 19114
    United States

    Site Not Available

  • Preferred Primary Care Physicians_Pittsburgh

    Pittsburgh 5206379, Pennsylvania 6254927 15236
    United States

    Site Not Available

  • AnMed Health IMA

    Anderson, South Carolina 29621
    United States

    Site Not Available

  • Novo Nordisk Investigational Site

    Anderson, South Carolina 29621
    United States

    Active - Recruiting

  • AnMed Health IMA

    Anderson 4569298, South Carolina 4597040 29621
    United States

    Site Not Available

  • Baylor Scott & White Res Inst

    Dallas, Texas 75246
    United States

    Site Not Available

  • Novo Nordisk Investigational Site

    Dallas, Texas 75246
    United States

    Active - Recruiting

  • Hill Country Medical Associates

    New Braunfels, Texas 78130
    United States

    Site Not Available

  • Novo Nordisk Investigational Site

    New Braunfels, Texas 78130
    United States

    Active - Recruiting

  • DCT-Stone Oak

    San Antonio, Texas 78258
    United States

    Site Not Available

  • Novo Nordisk Investigational Site

    San Antonio, Texas 78258
    United States

    Active - Recruiting

  • Baylor Scott & White Res Inst

    Dallas 4684888, Texas 4736286 75246
    United States

    Site Not Available

  • Hill Country Medical Associates

    New Braunfels 4714131, Texas 4736286 78130
    United States

    Site Not Available

  • DCT-Stone Oak

    San Antonio 4726206, Texas 4736286 78258
    United States

    Site Not Available

  • Chrysalis Clinical Research

    Saint George, Utah 84790
    United States

    Site Not Available

  • Novo Nordisk Investigational Site

    Saint George, Utah 84790
    United States

    Active - Recruiting

  • Chrysalis Clinical Research

    St. George 5546220, Utah 5549030 84790
    United States

    Site Not Available

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