Obesity Type 2 Diabetes MellitusNCT07566299

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

An observational study of Obesity Type 2 Diabetes Mellitus and Cardiovascular-kidney-metabolic Syndrome, run by Chung Shan Medical University.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Obesity Type 2 Diabetes Mellitus, Cardiovascular-kidney-metabolic Syndrome, Metabolic Dysfunction-Associated Steatotic Liver Disease
How many people: 118,805 participants
Where: No sites listed yet
Study dates: 1 Jan 2017to 31 Mar 2026
Phase: Observational
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

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. Four mutually exclusive cohorts were defined by background therapy (GLP-1 receptor agonist or SGLT2 inhibitor) and 90-day add-on status, supporting four prespecified pairwise comparisons of early complementary add-on against monotherapy or against usual-care add-on (DPP-4 inhibitor, sulfonylurea, or insulin).

Who may be able to join

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
New initiation of GLP-1 receptor agonist therapy or SGLT2 inhibitor therapy during the study period as background therapy
No prescription of either GLP-1 receptor agonist or SGLT2 inhibitor within the 6-month washout window before background therapy initiation

Who cannot join

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
Hepatocellular carcinoma or liver transplant within 1 year before background therapy initiation
Major cardiovascular, kidney, or liver event within the 6-month window before background therapy initiation
Transplant-related complications

About this study

Official title: 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 as background therapy. Within each background-therapy cohort, patients who added the complementary class within 90 days of initiation were compared against patients who did not, with prespecified comparisons against both the overall non-complementary cohort and the analytical subset who initiated usual-care add-on therapy (DPP-4 inhibitors, sulfonylureas, or insulin) within the same window. The primary outcome is all-cause mortality over 60 months, with major adverse cardiovascular, kidney, and liver outcomes also evaluated. Propensity-score matching is used to reduce bias from nonrandom treatment selection.

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

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT07566299
Study group	Role	What they receive
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.
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.

What is being measured

The primary outcome is the main question the study is designed to answer.

All-cause Mortality (Comparison 1)
All-cause mortality from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 1, comparing adults with obesity, type 2 diabetes, CKM syndrome stage 2-3, and MASLD who initiated GLP-1 RA therapy with early SGLT2i add-on versus those who initiated GLP-1 RA therapy without early SGLT2i add-on (monotherapy).
Measured: From 90 days after treatment initiation through up to 60 months of follow-up
All-cause Mortality (Comparison 2)
All-cause mortality from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 2, comparing adults with obesity, type 2 diabetes, CKM syndrome stage 2-3, and MASLD who initiated GLP-1 RA therapy with early SGLT2i add-on versus those who initiated GLP-1 RA therapy with usual care (DPP-4 inhibitor, sulfonylurea, or insulin add-on).
Measured: From 90 days after treatment initiation through up to 60 months of follow-up
All-cause Mortality (Comparison 3)
All-cause mortality from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 3, comparing adults with obesity, type 2 diabetes, CKM syndrome stage 2-3, and MASLD who initiated SGLT2i therapy with early GLP-1 RA add-on versus those who initiated SGLT2i therapy without early GLP-1 RA add-on (monotherapy).
Measured: From 90 days after treatment initiation through up to 60 months of follow-up
All-cause Mortality (Comparison 4)
All-cause mortality from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 4, comparing adults with obesity, type 2 diabetes, CKM syndrome stage 2-3, and MASLD who initiated SGLT2i therapy with early GLP-1 RA add-on versus those who initiated SGLT2i therapy with usual care (DPP-4 inhibitor, sulfonylurea, or insulin add-on).
Measured: From 90 days after treatment initiation through up to 60 months of follow-up

Secondary outcomes (12)

Major Adverse Cardiovascular Events (Comparison 1)
Composite of acute myocardial infarction, cardiac arrest, intracerebral or intracranial hemorrhage, and cerebral infarction from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 1, comparing GLP-1 RA with early SGLT2i add-on versus GLP-1 RA monotherapy.
Measured: From 90 days after treatment initiation through up to 60 months of follow-up
Major Adverse Cardiovascular Events (Comparison 2)
Composite of acute myocardial infarction, cardiac arrest, intracerebral or intracranial hemorrhage, and cerebral infarction from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 2, comparing GLP-1 RA with early SGLT2i add-on versus GLP-1 RA with usual care.
Measured: From 90 days after treatment initiation through up to 60 months of follow-up
Major Adverse Cardiovascular Events (Comparison 3)
Composite of acute myocardial infarction, cardiac arrest, intracerebral or intracranial hemorrhage, and cerebral infarction from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 3, comparing SGLT2i with early GLP-1 RA add-on versus SGLT2i monotherapy.
Measured: From 90 days after treatment initiation through up to 60 months of follow-up
Major Adverse Cardiovascular Events (Comparison 4)
Composite of acute myocardial infarction, cardiac arrest, intracerebral or intracranial hemorrhage, and cerebral infarction from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 4, comparing SGLT2i with early GLP-1 RA add-on versus SGLT2i with usual care.
Measured: From 90 days after treatment initiation through up to 60 months of follow-up
Major Adverse Kidney Events (Comparison 1)
Composite of end-stage kidney disease, dialysis dependence or initiation, kidney failure, and dialysis-related procedures from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 1, comparing GLP-1 RA with early SGLT2i add-on versus GLP-1 RA monotherapy.
Measured: From 90 days after treatment initiation through up to 60 months of follow-up
Major Adverse Kidney Events (Comparison 2)
Composite of end-stage kidney disease, dialysis dependence or initiation, kidney failure, and dialysis-related procedures from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 2, comparing GLP-1 RA with early SGLT2i add-on versus GLP-1 RA with usual care.
Measured: From 90 days after treatment initiation through up to 60 months of follow-up
Major Adverse Kidney Events (Comparison 3)
Composite of end-stage kidney disease, dialysis dependence or initiation, kidney failure, and dialysis-related procedures from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 3, comparing SGLT2i with early GLP-1 RA add-on versus SGLT2i monotherapy.
Measured: From 90 days after treatment initiation through up to 60 months of follow-up
Major Adverse Kidney Events (Comparison 4)
Composite of end-stage kidney disease, dialysis dependence or initiation, kidney failure, and dialysis-related procedures from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 4, comparing SGLT2i with early GLP-1 RA add-on versus SGLT2i with usual care.
Measured: From 90 days after treatment initiation through up to 60 months of follow-up
Major Adverse Liver Outcomes (Comparison 1)
Composite of hepatic decompensation (ascites, hepatic encephalopathy, variceal bleeding, spontaneous bacterial peritonitis, hepatic failure, hepatorenal syndrome), hepatocellular carcinoma, and liver transplantation from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 1, comparing GLP-1 RA with early SGLT2i add-on versus GLP-1 RA monotherapy.
Measured: From 90 days after treatment initiation through up to 60 months of follow-up
Major Adverse Liver Outcomes (Comparison 2)
Composite of hepatic decompensation, hepatocellular carcinoma, and liver transplantation from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 2, comparing GLP-1 RA with early SGLT2i add-on versus GLP-1 RA with usual care.
Measured: From 90 days after treatment initiation through up to 60 months of follow-up
Major Adverse Liver Outcomes (Comparison 3)
Composite of hepatic decompensation, hepatocellular carcinoma, and liver transplantation from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 3, comparing SGLT2i with early GLP-1 RA add-on versus SGLT2i monotherapy.
Measured: From 90 days after treatment initiation through up to 60 months of follow-up
Major Adverse Liver Outcomes (Comparison 4)
Composite of hepatic decompensation, hepatocellular carcinoma, and liver transplantation from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 4, comparing SGLT2i with early GLP-1 RA add-on versus SGLT2i with usual care.
Measured: From 90 days after treatment initiation through up to 60 months of follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jan 201731 Mar 2026

First posted5 May 2026
Study start1 Jan 2017
Primary completion31 Mar 2026
Study completion31 Mar 2026

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (34)Papers the sponsor has linked to this study.
Other trials for Obesity Type 2 Diabetes MellitusStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Cohort
Time perspective: Retrospective
Enrolment: 118,805 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07566299
Sponsor's protocol ID: CS1-26035
Status last verified: May 2026
First submitted: 26 Apr 2026
Last updated: 25 Jun 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No: 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.

Publications

Austin PC, Lee DS, Fine JP. Introduction to the Analysis of Survival Data in the Presence of Competing Risks. Circulation. 2016 Feb 9;133(6):601-9. doi: 10.1161/CIRCULATIONAHA.115.017719.
PubMed 26858290
Dafni U. Landmark analysis at the 25-year landmark point. Circ Cardiovasc Qual Outcomes. 2011 May;4(3):363-71. doi: 10.1161/CIRCOUTCOMES.110.957951.
PubMed 21586725
Lipsitch M, Tchetgen Tchetgen E, Cohen T. Negative controls: a tool for detecting confounding and bias in observational studies. Epidemiology. 2010 May;21(3):383-8. doi: 10.1097/EDE.0b013e3181d61eeb.
PubMed 20335814
Austin PC. An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies. Multivariate Behav Res. 2011 May;46(3):399-424. doi: 10.1080/00273171.2011.568786. Epub 2011 Jun 8.
PubMed 21818162
Matthews AA, Danaei G, Islam N, Kurth T. Target trial emulation: applying principles of randomised trials to observational studies. BMJ. 2022 Aug 30;378:e071108. doi: 10.1136/bmj-2022-071108. No abstract available.
PubMed 36041749
Hernan MA, Wang W, Leaf DE. Target Trial Emulation: A Framework for Causal Inference From Observational Data. JAMA. 2022 Dec 27;328(24):2446-2447. doi: 10.1001/jama.2022.21383.
PubMed 36508210
Hernan MA, Robins JM. Using Big Data to Emulate a Target Trial When a Randomized Trial Is Not Available. Am J Epidemiol. 2016 Apr 15;183(8):758-64. doi: 10.1093/aje/kwv254. Epub 2016 Mar 18.
PubMed 26994063
Topaloglu U, Palchuk MB. Using a Federated Network of Real-World Data to Optimize Clinical Trials Operations. JCO Clin Cancer Inform. 2018 Dec;2:1-10. doi: 10.1200/CCI.17.00067.
PubMed 30652541
Palchuk MB, London JW, Perez-Rey D, Drebert ZJ, Winer-Jones JP, Thompson CN, Esposito J, Claerhout B. A global federated real-world data and analytics platform for research. JAMIA Open. 2023 May 13;6(2):ooad035. doi: 10.1093/jamiaopen/ooad035. eCollection 2023 Jul.
PubMed 37193038
Wright AK, Carr MJ, Kontopantelis E, Leelarathna L, Thabit H, Emsley R, Buchan I, Mamas MA, van Staa TP, Sattar N, Ashcroft DM, Rutter MK. Primary Prevention of Cardiovascular and Heart Failure Events With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Their Combination in Type 2 Diabetes. Diabetes Care. 2022 Apr 1;45(4):909-918. doi: 10.2337/dc21-1113.
PubMed 35100355
Neuen BL, Fletcher RA, Heath L, Perkovic A, Vaduganathan M, Badve SV, Tuttle KR, Pratley R, Gerstein HC, Perkovic V, Heerspink HJL. Cardiovascular, Kidney, and Safety Outcomes With GLP-1 Receptor Agonists Alone and in Combination With SGLT2 Inhibitors in Type 2 Diabetes: A Systematic Review and Meta-Analysis. Circulation. 2024 Nov 26;150(22):1781-1790. doi: 10.1161/CIRCULATIONAHA.124.071689. Epub 2024 Aug 30.
PubMed 39210781
Simms-Williams N, Treves N, Yin H, Lu S, Yu O, Pradhan R, Renoux C, Suissa S, Azoulay L. Effect of combination treatment with glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors on incidence of cardiovascular and serious renal events: population based cohort study. BMJ. 2024 Apr 25;385:e078242. doi: 10.1136/bmj-2023-078242.
PubMed 38663919
Mantovani A, Petracca G, Csermely A, Beatrice G, Targher G. Sodium-Glucose Cotransporter-2 Inhibitors for Treatment of Nonalcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trials. Metabolites. 2020 Dec 30;11(1):22. doi: 10.3390/metabo11010022.
PubMed 33396949
Loomba R, Hartman ML, Lawitz EJ, Vuppalanchi R, Boursier J, Bugianesi E, Yoneda M, Behling C, Cummings OW, Tang Y, Brouwers B, Robins DA, Nikooie A, Bunck MC, Haupt A, Sanyal AJ; SYNERGY-NASH Investigators. Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis. N Engl J Med. 2024 Jul 25;391(4):299-310. doi: 10.1056/NEJMoa2401943. Epub 2024 Jun 8.
PubMed 38856224
Sanyal AJ, Newsome PN, Kliers I, Ostergaard LH, Long MT, Kjaer MS, Cali AMG, Bugianesi E, Rinella ME, Roden M, Ratziu V; ESSENCE Study Group. Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis. N Engl J Med. 2025 Jun 5;392(21):2089-2099. doi: 10.1056/NEJMoa2413258. Epub 2025 Apr 30.
PubMed 40305708

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Use and Acceptability of an AI-Assisted Health Application for Individuals Living With a Chronic Condition
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Obesity and Diabetes Mellitus, Type 2, Albuminuria

All Obesity Type 2 Diabetes Mellitus trials

Study at a glance

From the registry record, last updated by the sponsor on 25 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT07566299
Acronym / sponsor ID: CS1-26035
Conditions: Obesity Type 2 Diabetes Mellitus, Cardiovascular-kidney-metabolic Syndrome, Metabolic Dysfunction-Associated Steatotic Liver Disease
Study type: Observational
Recruitment status: Completed
Enrolment: 118,805 participants (actual)
Lead sponsor: Chung Shan Medical UniversityUniversity, hospital or other
Collaborators: National Science and Technology Council, Taiwan
Study start: 1 Jan 2017 (actual)
Primary completion: 31 Mar 2026 (actual)
Study completion: 31 Mar 2026 (actual)
First posted: 5 May 2026 (actual)
Results: Posted 25 Jun 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Observational model: Cohort
Time perspective: Retrospective
Number of arms: 4

Arm	Type	Receives
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.
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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
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. Four mutually exclusive cohorts were defined by background therapy (GLP-1 receptor agonist or SGLT2 inhibitor) and 90-day add-on status, supporting four prespecified pairwise comparisons of early complementary add-on against monotherapy or against usual-care add-on (DPP-4 inhibitor, sulfonylurea, or insulin).

Key inclusion criteria (7 listed)

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

Key exclusion criteria (8 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Primary outcome

All-cause Mortality (Comparison 1)
Time frame: From 90 days after treatment initiation through up to 60 months of follow-up
All-cause mortality from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 1, comparing adults with obesity, type 2 diabetes, CKM syndrome stage 2-3, and MASLD who initiated GLP-1 RA therapy with early SGLT2i add-on versus those who initiated GLP-1 RA therapy without early SGLT2i add-on (monotherapy).
All-cause Mortality (Comparison 2)
Time frame: From 90 days after treatment initiation through up to 60 months of follow-up
All-cause mortality from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 2, comparing adults with obesity, type 2 diabetes, CKM syndrome stage 2-3, and MASLD who initiated GLP-1 RA therapy with early SGLT2i add-on versus those who initiated GLP-1 RA therapy with usual care (DPP-4 inhibitor, sulfonylurea, or insulin add-on).
All-cause Mortality (Comparison 3)
Time frame: From 90 days after treatment initiation through up to 60 months of follow-up
All-cause mortality from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 3, comparing adults with obesity, type 2 diabetes, CKM syndrome stage 2-3, and MASLD who initiated SGLT2i therapy with early GLP-1 RA add-on versus those who initiated SGLT2i therapy without early GLP-1 RA add-on (monotherapy).
All-cause Mortality (Comparison 4)
Time frame: From 90 days after treatment initiation through up to 60 months of follow-up
All-cause mortality from the 90-day landmark date through up to 60 months of follow-up in the propensity score-matched cohort for Comparison 4, comparing adults with obesity, type 2 diabetes, CKM syndrome stage 2-3, and MASLD who initiated SGLT2i therapy with early GLP-1 RA add-on versus those who initiated SGLT2i therapy with usual care (DPP-4 inhibitor, sulfonylurea, or insulin add-on).

12 secondary outcomes

Major Adverse Cardiovascular Events (Comparison 1)
Time frame: From 90 days after treatment initiation through up to 60 months of follow-up
Major Adverse Cardiovascular Events (Comparison 2)
Time frame: From 90 days after treatment initiation through up to 60 months of follow-up
Major Adverse Cardiovascular Events (Comparison 3)
Time frame: From 90 days after treatment initiation through up to 60 months of follow-up
Major Adverse Cardiovascular Events (Comparison 4)
Time frame: From 90 days after treatment initiation through up to 60 months of follow-up
Major Adverse Kidney Events (Comparison 1)
Time frame: From 90 days after treatment initiation through up to 60 months of follow-up
Major Adverse Kidney Events (Comparison 2)
Time frame: From 90 days after treatment initiation through up to 60 months of follow-up
Major Adverse Kidney Events (Comparison 3)
Time frame: From 90 days after treatment initiation through up to 60 months of follow-up
Major Adverse Kidney Events (Comparison 4)
Time frame: From 90 days after treatment initiation through up to 60 months of follow-up
Major Adverse Liver Outcomes (Comparison 1)
Time frame: From 90 days after treatment initiation through up to 60 months of follow-up
Major Adverse Liver Outcomes (Comparison 2)
Time frame: From 90 days after treatment initiation through up to 60 months of follow-up
Major Adverse Liver Outcomes (Comparison 3)
Time frame: From 90 days after treatment initiation through up to 60 months of follow-up
Major Adverse Liver Outcomes (Comparison 4)
Time frame: From 90 days after treatment initiation through up to 60 months of follow-up

Results and safety

Results posted to the registry on 25 Jun 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
GLP-1 RA With SGLT2i Add-On	14,542	14,542
GLP-1 RA Monotherapy	57,166	57,166
SGLT2i With GLP-1 RA Add-On	13,680	13,680
SGLT2i Monotherapy	33,417	33,417

Primary outcome: All-cause Mortality (Comparison 1)

Time frame: From 90 days after treatment initiation through up to 60 months of follow-up. Number. Unit: participants with event

Measure	GLP-1 RA With SGLT2i Add-On (Comparison 1) n = 14358	GLP-1 RA Monotherapy (Comparison 1) n = 14389
Value	278	396

Population analysed: Participants analyzed were members of the corresponding comparison-specific propensity score-matched cohort who were at risk at the start of the 60-month assessment window. Participants with the outcome before the assessment window were excluded. Therefore, the number analyzed may differ across outcomes.

Primary outcome: All-cause Mortality (Comparison 2)

Time frame: From 90 days after treatment initiation through up to 60 months of follow-up. Number. Unit: participants with event

Measure	GLP-1 RA With SGLT2i Add-On (Comparison 2) n = 12897	GLP-1 RA With Usual Care (Comparison 2) n = 12865
Value	248	425

Primary outcome: All-cause Mortality (Comparison 3)

Time frame: From 90 days after treatment initiation through up to 60 months of follow-up. Number. Unit: participants with event

Measure	SGLT2i With GLP-1 RA Add-On (Comparison 3) n = 13359	SGLT2i Monotherapy (Comparison 3) n = 13345
Value	290	418

Primary outcome: All-cause Mortality (Comparison 4)

Time frame: From 90 days after treatment initiation through up to 60 months of follow-up. Number. Unit: participants with event

Measure	SGLT2i With GLP-1 RA Add-On (Comparison 4) n = 11034	SGLT2i With Usual Care (Comparison 4) n = 10974
Value	270	402

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the 90-day landmark date through up to 60 months of follow-up. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
GLP-1 RA With SGLT2i Add-On (Comparison 1)	608 of 14,303 (4.3%)	0 of 0	278 of 14,358
GLP-1 RA Monotherapy (Comparison 1)	715 of 14,276 (5%)	0 of 0	396 of 14,389
GLP-1 RA With SGLT2i Add-On (Comparison 2)	574 of 12,848 (4.5%)	0 of 0	248 of 12,897
GLP-1 RA With Usual Care (Comparison 2)	754 of 12,798 (5.9%)	0 of 0	425 of 12,865
SGLT2i With GLP-1 RA Add-On (Comparison 3)	548 of 13,297 (4.1%)	0 of 0	290 of 13,359
SGLT2i Monotherapy (Comparison 3)	667 of 13,302 (5%)	0 of 0	418 of 13,345
SGLT2i With GLP-1 RA Add-On (Comparison 4)	484 of 10,977 (4.4%)	0 of 0	270 of 11,034
SGLT2i With Usual Care (Comparison 4)	613 of 10,949 (5.6%)	0 of 0	402 of 10,974

Limitations and caveats (from the sponsor): As a retrospective observational study using routinely collected electronic health record data, this analysis may be subject to residual confounding, exposure and outcome misclassification, and incomplete capture of clinical variables. The 90-day landmark design excludes early outcome events. MASLD and CKM stage 2-3 definitions depend on diagnosis coding and available laboratory data. Observed associations should not be interpreted as evidence of a treatment effect.

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Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 26858290Austin PC, Lee DS, Fine JP. Introduction to the Analysis of Survival Data in the Presence of Competing Risks. Circulation. 2016 Feb 9;133(6):601-9. doi: 10.1161/CIRCULATIONAHA.115.017719.
Background: PubMed 21586725Dafni U. Landmark analysis at the 25-year landmark point. Circ Cardiovasc Qual Outcomes. 2011 May;4(3):363-71. doi: 10.1161/CIRCOUTCOMES.110.957951.
Background: PubMed 20335814Lipsitch M, Tchetgen Tchetgen E, Cohen T. Negative controls: a tool for detecting confounding and bias in observational studies. Epidemiology. 2010 May;21(3):383-8. doi: 10.1097/EDE.0b013e3181d61eeb.
Background: PubMed 21818162Austin PC. An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies. Multivariate Behav Res. 2011 May;46(3):399-424. doi: 10.1080/00273171.2011.568786. Epub 2011 Jun 8.
Background: PubMed 36041749Matthews AA, Danaei G, Islam N, Kurth T. Target trial emulation: applying principles of randomised trials to observational studies. BMJ. 2022 Aug 30;378:e071108. doi: 10.1136/bmj-2022-071108. No abstract available.
Background: PubMed 36508210Hernan MA, Wang W, Leaf DE. Target Trial Emulation: A Framework for Causal Inference From Observational Data. JAMA. 2022 Dec 27;328(24):2446-2447. doi: 10.1001/jama.2022.21383.
Background: PubMed 26994063Hernan MA, Robins JM. Using Big Data to Emulate a Target Trial When a Randomized Trial Is Not Available. Am J Epidemiol. 2016 Apr 15;183(8):758-64. doi: 10.1093/aje/kwv254. Epub 2016 Mar 18.
Background: PubMed 30652541Topaloglu U, Palchuk MB. Using a Federated Network of Real-World Data to Optimize Clinical Trials Operations. JCO Clin Cancer Inform. 2018 Dec;2:1-10. doi: 10.1200/CCI.17.00067.
Background: PubMed 37193038Palchuk MB, London JW, Perez-Rey D, Drebert ZJ, Winer-Jones JP, Thompson CN, Esposito J, Claerhout B. A global federated real-world data and analytics platform for research. JAMIA Open. 2023 May 13;6(2):ooad035. doi: 10.1093/jamiaopen/ooad035. eCollection 2023 Jul.
Background: PubMed 35100355Wright AK, Carr MJ, Kontopantelis E, Leelarathna L, Thabit H, Emsley R, Buchan I, Mamas MA, van Staa TP, Sattar N, Ashcroft DM, Rutter MK. Primary Prevention of Cardiovascular and Heart Failure Events With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Their Combination in Type 2 Diabetes. Diabetes Care. 2022 Apr 1;45(4):909-918. doi: 10.2337/dc21-1113.
Background: PubMed 39210781Neuen BL, Fletcher RA, Heath L, Perkovic A, Vaduganathan M, Badve SV, Tuttle KR, Pratley R, Gerstein HC, Perkovic V, Heerspink HJL. Cardiovascular, Kidney, and Safety Outcomes With GLP-1 Receptor Agonists Alone and in Combination With SGLT2 Inhibitors in Type 2 Diabetes: A Systematic Review and Meta-Analysis. Circulation. 2024 Nov 26;150(22):1781-1790. doi: 10.1161/CIRCULATIONAHA.124.071689. Epub 2024 Aug 30.
Background: PubMed 38663919Simms-Williams N, Treves N, Yin H, Lu S, Yu O, Pradhan R, Renoux C, Suissa S, Azoulay L. Effect of combination treatment with glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors on incidence of cardiovascular and serious renal events: population based cohort study. BMJ. 2024 Apr 25;385:e078242. doi: 10.1136/bmj-2023-078242.
Individual participant dataSharing planned: No. 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

Questions about this trial

What is this clinical trial studying?

An observational study of Obesity Type 2 Diabetes Mellitus and Cardiovascular-kidney-metabolic Syndrome, run by Chung Shan Medical University.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

All-cause Mortality (Comparison 1) (time frame: From 90 days after treatment initiation through up to 60 months of follow-up). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07566299, which also lists 34 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2026.