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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: semaglutide; Drug: oral glucose-lowering medications (commercially available)

• Study Type: Interventional
• Enrollment (Actual): 1018
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Alhambra, California, United States, 91801
      • Stewart Medical Group
    • Costa Mesa, California, United States, 92627
      • FDRC
    • La Jolla, California, United States, 92037
      • Scripps Whittier Diabetes Inst
    • Riverside, California, United States, 92506
      • Raincross Medical Group
  • Florida
    • Miami, Florida, United States, 33175
      • Reyes Clinical Research, Inc
  • Georgia
    • Marietta, Georgia, United States, 30067
      • Urban Family Practice Assoc
    • Marietta, Georgia, United States, 30060
      • DC Research Works
  • Illinois
    • Gillespie, Illinois, United States, 62033
      • Macoupin Research Group
    • Peoria, Illinois, United States, 61603
      • UnityPoint Health-Diabetes Care Center
    • Skokie, Illinois, United States, 60077
      • Endeavor Health
  • North Carolina
    • Burlington, North Carolina, United States, 27215
      • Kernodle Clin Dpt-Pvt Diagnost
    • Charlotte, North Carolina, United States, 28277
      • OnSite Clinical Solutions, LLC_Charlotte
    • Garner, North Carolina, United States, 27529
      • WakeMed Garner Hlthplx
    • Gastonia, North Carolina, United States, 28054
      • Clinical Research of Gastonia
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Valley Weight Loss Clinic
  • Ohio
    • Canton, Ohio, United States, 44718
      • Diab & Endo Assoc of Stark Co
    • Columbus, Ohio, United States, 43213
      • Central Ohio Clinical Research LLC
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19114
      • Tristar Clin Investigations, PC
    • Philadelphia, Pennsylvania, United States, 19107-6810
      • Jefferson Endocrinology Assocs
    • Pittsburgh, Pennsylvania, United States, 15236
      • Preferred Primary Care Physicians_Pittsburgh
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health IMA
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor Scott & White Res Inst
    • New Braunfels, Texas, United States, 78130
      • Hill Country Medical Associates
    • San Antonio, Texas, United States, 78258
      • DCT-Stone Oak
  • Utah
    • St. George, Utah, United States, 84790
      • Chrysalis Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: oral semaglutide; All participants are given tablets used in addition to metformin.	Drug: semaglutide; Oral administration The doctor will give a prescription for the medicine and tell how to take it.
Active Comparator: other oral glucose lowering medication; All participants are given tablets used in addition to metformin.	Drug: oral glucose-lowering medications (commercially available); Oral administration The doctor will give a prescription for the medicine and tell how to take it.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Glycated Haemoglobin (HbA1c)	Change in HbA1c in percentage from week 0 to year 1 is presented	Week 0, year 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants Achieving HbA1c Less Than (<) 7.0 Percentage (%) (Yes /No)	Participants achieving HbA1c < 7.0% (Yes /No) at year 1 is presented. 'Yes' defines participants who achieved HbA1c < 7.0% and 'No' defines participants who did not achieve HbA1c < 7.0 %.	At year 1
Participants Achieving HbA1c Less Than or Equal to (≤) 6.5% (Yes/No)	Participants achieving HbA1c ≤ 6.5% (Yes/No) at year 1 is presented. 'Yes' defines participants who achieved HbA1c ≤ 6.5% and 'No' defines participants who did not achieve HbA1c ≤ 6.5%.	At year 1
Participants Achieving HbA1c <7.0% or at Least 1.0%-Point Reduction in HbA1c (Yes/No)	Participants achieving HbA1c < 7.0% or at least 1.0%-point reduction in HbA1c (Yes/No) from week 0 to year 1 is presented. 'Yes' defines participants who achieved HbA1c < 7.0% or reduction of at least 1.0%-point in HbA1c and 'No' defines participants who did not achieve HbA1c < 7.0% or reduction of at least 1.0%-point in HbA1c.	From Week 0 to year 1
Participants Achieving Greater Than or Equal to (≥) 5% Reduction in Body Weight (Yes/No)	Participants achieving ≥ 5% reduction in body weight (Yes/No) from week 0 to year 1 is presented. 'Yes' defines participants who achieved ≥ 5% reduction in body weight and 'No' defines participants who did not achieve ≥ 5% reduction in body weight.	From week 0 to year 1
Participant Achieving Individualized HbA1c Target Per Healthcare Effectiveness Data and Information Set (HEDIS) Criteria (Yes/No)	Participants achieving individualized HbA1c target per HEDIS criteria (< 8.0% if age ≥ 65 years or with defined comorbidities or otherwise < 7.0%) (Yes/No) at year 1 is presented. 'Yes' defines participants who achieved individualized HbA1c target per HEDIS criteria and 'No' defines participants who did not achieve individualized HbA1c target per HEDIS criteria.	At year 1
Participant Achieving HbA1c ≤ Treatment Provider Defined Individualized Target (Yes/No)	Participant achieving HbA1c ≤ treatment provider defined individualized target (Yes/No) at year 1 is presented. 'Yes' defines participant who achieved HbA1c ≤ treatment provider defined individualized target and 'No' defines participant who did not achieve HbA1c ≤ treatment provider defined individualized target.	At year 1
Relative Change in Body Weight (%)	Relative change in body weight from week 0 to year 1 is presented.	Week 0, year 1
Change in Body Weight (Lbs)	Change in body weight in pounds (lbs) from week 0 to year 1 is presented.	Week 0, year 1
Time to Treatment Intensification (add-on) or Change (Switch) in Terms of Events	Time to treatment intensification (add-on) or change (switch) in terms of events from week 0 to year 1 is presented.	From week 0 to year 1
Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc), Relative Treatment Satisfaction Total Score	DTSQc relative treatment satisfaction total score measured at year 1 is presented. DTSQc are used to evaluate patient satisfaction with treatment. The measure consists of 8 items, 6 of which assess treatment satisfaction. Scores from the 6 treatment satisfaction items are summed to a total treatment satisfaction score, which ranges from -18 (much less satisfied) to +18 (much more satisfied).	At year 1

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency (dept. 1452), Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Actual): June 18, 2025
• Study Completion (Actual): June 18, 2025

Study Registration Dates

• First Submitted: August 30, 2021
• First Submitted That Met QC Criteria: August 30, 2021
• First Posted (Actual): September 5, 2021

Study Record Updates

• Last Update Posted (Actual): August 10, 2026
• Last Update Submitted That Met QC Criteria: August 6, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; semaglutide
• Other Study ID Numbers: NN9924-4558; U1111-1253-2577 (Other Identifier: World Health Organization (WHO))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes