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

NCT07566299 | Not Yet Recruiting

• 1 other identifier: CS1-26035
• Study Type: observational
• Target: 118,805
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Obesity Type 2 Diabetes Mellitus; Cardiovascular-kidney-metabolic Syndrome; Metabolic Dysfunction-Associated Steatotic Liver Disease

Outcome Measures

Primary Outcomes (1)

• All-cause mortality

  From 90 days after treatment initiation through up to 60 months of follow-up

Secondary Outcomes (3)

• Major Adverse Cardiovascular Events

  From 90 days after treatment initiation through up to 60 months of follow-up

• Major Adverse Kidney Events

  From 90 days after treatment initiation through up to 60 months of follow-up

• Major Adverse Liver Outcomes

  From 90 days after treatment initiation through up to 60 months of follow-up

Study Arms (6)

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.

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Chung Shan Medical University: lead
• National Science and Technology Council, Taiwan: collaborator

Study Sites (1)

Chung Shan Medical University Hospital

Taichung, Taichung, 402, Taiwan

Location

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Central Study Contacts

Pen-Hua Su, PhD

CONTACT

886-4-24739595; jen@csh.org.tw

Yu-Nan Huang, PhD

CONTACT

886-4-24739595; yunanhuang83@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor/Research Fellow

Study Record Dates

• First Submitted: April 26, 2026
• First Posted: May 5, 2026
• Study Start (Estimated): May 31, 2026
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)