Early GLP-1 Receptor Agonist and SGLT2 Inhibitor Add-On Strategies in Adults With Obesity, Type 2 Diabetes, Cardiovascular-Kidney-Metabolic Syndrome Stage 2-3, and Metabolic Dysfunction-Associated Steatotic Liver Disease

April 29, 2026 updated by: Yu-Nan Huang, Chung Shan Medical University

Early GLP-1 Receptor Agonist and SGLT2 Inhibitor Add-On Strategies in Adults With Obesity, Type 2 Diabetes, Cardiovascular-Kidney-Metabolic Syndrome Stage 2-3, and Metabolic Dysfunction-Associated Steatotic Liver Disease: A Target Trial Emulation

This retrospective observational target-trial emulation uses electronic health record data from the TriNetX US Collaborative Network to compare early treatment intensification strategies in adults with obesity, type 2 diabetes, cardiovascular-kidney-metabolic syndrome stage 2-3, and metabolic dysfunction-associated steatotic liver disease who initiate a GLP-1 receptor agonist or an SGLT2 inhibitor. The study compares patients who, within 90 days of starting background therapy, add the alternate agent, add usual-care glucose-lowering therapy, or do not receive early add-on therapy. Usual-care add-on therapy includes DPP-4 inhibitors, sulfonylureas, or insulin. The primary outcome is all-cause mortality over 60 months, with major cardiovascular events, major kidney events, and major liver outcomes also evaluated. Propensity-score methods are used to reduce bias from nonrandom treatment selection.

Study Overview

Status

Not yet recruiting

Conditions

Study Type

Observational

Enrollment (Estimated)

118805

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Pen-Hua Su, PhD
  • Phone Number: 21707 886-4-24739595
  • Email: jen@csh.org.tw

Study Contact Backup

Study Locations

  • Taiwan
    • Taichung
      • Taichung, Taichung, Taiwan, 402
        • Chung Shan Medical University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Adults will be selected from the TriNetX US Collaborative Network, a distributed database of de-identified electronic health records contributed by participating healthcare organizations across multiple clinical systems and practice settings. The study population consists of adults with obesity, type 2 diabetes, cardiovascular-kidney-metabolic syndrome stage 2-3, and metabolic dysfunction-associated steatotic liver disease who received routine clinical care in this network and were identified through diagnosis records, body mass index data, laboratory data, and medication prescribing data. Comparator-specific cohorts were defined within this source population to evaluate early GLP-1 receptor agonist- and SGLT2 inhibitor-based treatment strategies.

Description

Inclusion Criteria:

  • Adults aged 18 years or older.
  • BMI ≥27 kg/m², or diagnosis codes consistent with obesity
  • Type 2 diabetes mellitus
  • Cardiovascular-kidney-metabolic syndrome stage 2-3
  • Metabolic dysfunction-associated steatotic liver disease
  • Initiation of GLP-1 receptor agonist therapy or SGLT2 inhibitor therapy during the study period

Exclusion Criteria:

  • Type 1 diabetes mellitus, or other specified diabetes types that are not type 2 diabetes
  • Human immunodeficiency virus infection
  • Other chronic, alcohol-related, or secondary liver diseases
  • Prior bariatric surgery
  • Prior solid-organ transplantation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
GLP-1 RA with SGLT2i Add-On
Adults with obesity, type 2 diabetes, cardiovascular-kidney-metabolic syndrome stage 2-3, and metabolic dysfunction-associated steatotic liver disease who initiated GLP-1 receptor agonist therapy and added an SGLT2 inhibitor within 90 days after treatment initiation.
GLP-1 RA monotherapy
Adults with obesity, type 2 diabetes, cardiovascular-kidney-metabolic syndrome stage 2-3, and metabolic dysfunction-associated steatotic liver disease who initiated GLP-1 receptor agonist therapy and did not receive early add-on therapy with an SGLT2 inhibitor within 90 days after treatment initiation.
GLP-1 RA with usual care
Adults with obesity, type 2 diabetes, cardiovascular-kidney-metabolic syndrome stage 2-3, and metabolic dysfunction-associated steatotic liver disease who initiated GLP-1 receptor agonist therapy and received early usual-care glucose-lowering add-on therapy with a DPP-4 inhibitor, sulfonylurea, or insulin within 90 days after treatment initiation, without early SGLT2 inhibitor add-on therapy.
SGLT2i with GLP-1 RA Add-On
Adults with obesity, type 2 diabetes, cardiovascular-kidney-metabolic syndrome stage 2-3, and metabolic dysfunction-associated steatotic liver disease who initiated SGLT2 inhibitor therapy and added a GLP-1 receptor agonist within 90 days after treatment initiation.
SGLT2i monotherapy
Adults with obesity, type 2 diabetes, cardiovascular-kidney-metabolic syndrome stage 2-3, and metabolic dysfunction-associated steatotic liver disease who initiated SGLT2 inhibitor therapy and did not receive early add-on therapy with a GLP-1 receptor agonist within 90 days after treatment initiation.
SGLT2i with usual care
Adults with obesity, type 2 diabetes, cardiovascular-kidney-metabolic syndrome stage 2-3, and metabolic dysfunction-associated steatotic liver disease who initiated SGLT2 inhibitor therapy and received early usual-care glucose-lowering add-on therapy with a DPP-4 inhibitor, sulfonylurea, or insulin within 90 days after treatment initiation, without early GLP-1 receptor agonist add-on therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
All-cause mortality
Time Frame: From 90 days after treatment initiation through up to 60 months of follow-up
From 90 days after treatment initiation through up to 60 months of follow-up

Secondary Outcome Measures

Outcome Measure
Time Frame
Major Adverse Cardiovascular Events
Time Frame: From 90 days after treatment initiation through up to 60 months of follow-up
From 90 days after treatment initiation through up to 60 months of follow-up
Major Adverse Kidney Events
Time Frame: From 90 days after treatment initiation through up to 60 months of follow-up
From 90 days after treatment initiation through up to 60 months of follow-up
Major Adverse Liver Outcomes
Time Frame: From 90 days after treatment initiation through up to 60 months of follow-up
From 90 days after treatment initiation through up to 60 months of follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chung Shan Medical University

Collaborators

National Science and Technology Council, Taiwan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 31, 2026

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

June 30, 2026

Study Registration Dates

First Submitted

April 26, 2026

First Submitted That Met QC Criteria

April 29, 2026

First Posted (Actual)

May 5, 2026

Study Record Updates

Last Update Posted (Actual)

May 5, 2026

Last Update Submitted That Met QC Criteria

April 29, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Other Study ID Numbers

  • CS1-26035

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data will not be shared. This retrospective observational study uses de-identified electronic health record data from the TriNetX US Collaborative Network. Access to individual-level data is restricted by data use agreements, institutional policies, and privacy protections. Researchers who meet eligibility requirements may obtain access to similar de-identified data through a TriNetX license or through participating institutions.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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