Cardiovascular-kidney-metabolic SyndromeGLP1-SGLT2-CKMNCT07465926

Early Add-On Combination of GLP-1 Receptor Agonist and SGLT2 Inhibitor in People With Cardiovascular-Kidney-Metabolic Stage 2-3

An observational study of Cardiovascular-kidney-metabolic Syndrome and Cardiovascular Disease Risk Factor, 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 20 years and older
Conditions the study is for: Cardiovascular-kidney-metabolic Syndrome, Cardiovascular Disease Risk Factor, Kidney Disease
What is being tested?: GLP-1 receptor agonist and SGLT2 inhibitor
How many people: 451,036 participants
Where: No sites listed yet
Study dates: 1 Jan 2017to 31 Jan 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 20 years and older
All sexes
No healthy volunteers
Adult, Older adult

Study population: Adults (≥20 years) with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3 identified from routinely collected electronic health record data in the TriNetX US Collaborative Network. Participants initiated a GLP-1 receptor agonist or an SGLT2 inhibitor and were classified according to early add-on treatment strategies.

Who may be able to join

Adults aged 20 years or older.
Obesity, defined by body mass index (BMI) 27 kg/m2 or greater.
Type 2 diabetes mellitus, defined using electronic health record data, including diagnosis codes and/or hemoglobin A1c 6.5% or greater.
Met cardiovascular-kidney-metabolic (CKM) stage 2-3 criteria at baseline.
Initiated a GLP-1 receptor agonist or an SGLT2 inhibitor as background therapy.
Had treatment strategy classification based on early add-on initiation within 90 days after background therapy initiation, or no early add-on with index at the 90-day landmark.

Who cannot join

Prior use of GLP-1 receptor agonists, SGLT2 inhibitors, DPP-4 inhibitors, or sulfonylureas within 6 months before cohort entry.
Major cardiovascular disease or revascularization within 12 months before cohort entry.
Advanced kidney disease within 12 months before cohort entry, including end-stage kidney disease, dialysis, or estimated glomerular filtration rate less than 15 mL/min/1.73 m2.
Major cardiovascular or renal events within 6 months before index.
Any history of non-type 2 diabetes, HIV infection, bariatric surgery, or solid-organ transplantation.
Missing critical baseline covariates.

About this study

Official title: Associations of Early Add-On GLP-1 Receptor Agonist and SGLT2 Inhibitor Therapy With Mortality and Kidney Outcomes in Adults With Obesity and Type 2 Diabetes Across Cardiovascular-Kidney-Metabolic Stages 2-3: 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, and cardiovascular-kidney-metabolic stage 2-3 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 a DPP-4 inhibitor or sulfonylurea, or do not receive early add-on therapy. The primary outcome is all-cause mortality over 36 months, with secondary cardiorenal outcomes also evaluated. Propensity-score methods are used to reduce bias from nonrandom treatment selection.

Read the detailed description

This study is a retrospective observational target-trial emulation using electronic health record data from the TriNetX US Collaborative Network. It evaluates early treatment intensification strategies after initiation of a GLP-1 receptor agonist or an SGLT2 inhibitor in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3.

Patients are grouped according to treatment changes made within 90 days after treatment initiation, including addition of the alternate drug class, addition of a DPP-4 inhibitor or sulfonylurea, or no early add-on treatment. Follow-up is aligned across comparison groups after this initial treatment assessment period.

The study uses routinely collected clinical data to assess the comparative effectiveness of these strategies on mortality and cardiorenal outcomes in real-world practice. Propensity-score-based methods are used to reduce confounding associated with nonrandom treatment selection.

Conditions: Cardiovascular-kidney-metabolic Syndrome, Cardiovascular Disease Risk Factor, Kidney Disease, Type 2 Diabetes, Obesity & Overweight
Being tested: GLP-1 receptor agonist, SGLT2 inhibitor
Keywords: GLP-1 RA, SGLT2i, Target trial emulation, TriNetX, Cardiovascular-Kidney-Metabolic Syndrome, Obesity, T2D
Medical subject headings: Kidney Diseases, Diabetes Mellitus, Type 2, Obesity, Overweight

What participants receive

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

GLP-1 receptor agonistDrug
Use of a glucagon-like peptide-1 receptor agonist as background therapy or add-on therapy in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3.
SGLT2 inhibitorDrug
Use of a sodium-glucose cotransporter-2 inhibitor as background therapy or add-on therapy in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3.

Study groups in NCT07465926
Study group	Role	What they receive
GLP-1 RA Base Therapy		Adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3 who initiated a GLP-1 receptor agonist as base therapy after a 6-month washout from GLP-1 RA, SGLT2i, DPP-4i, and sulfonylureas. Within this cohort, participants were classified by the first add-on treatment within 90 days into three mutually exclusive strategies: SGLT2i add-on, DPP-4i or sulfonylurea add-on, or no early add-on. Receives: Drug: GLP-1 receptor agonist; Drug: SGLT2 inhibitor
SGLT2i Base Therapy		Adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3 who initiated an SGLT2 inhibitor as base therapy after a 6-month washout from GLP-1 RA, SGLT2i, DPP-4i, and sulfonylureas. Within this cohort, participants were classified by the first add-on treatment within 90 days into three mutually exclusive strategies: GLP-1 RA add-on, DPP-4i or sulfonylurea add-on, or no early add-on. Receives: Drug: GLP-1 receptor agonist; Drug: SGLT2 inhibitor

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 within 36 months in the propensity score-matched cohort for Comparison 1, comparing GLP-1 RA with SGLT2i add-on versus GLP-1 RA with DPP-4 inhibitor or sulfonylurea add-on in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3.
Measured: From index through 36 months
All-cause Mortality (Comparison 2)
All-cause mortality within 36 months in the propensity score-matched cohort for Comparison 2, comparing GLP-1 RA with SGLT2i add-on versus GLP-1 RA without early add-on treatment in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3.
Measured: From index through 36 months
All-cause Mortality (Comparison 3)
All-cause mortality within 36 months in the propensity score-matched cohort for Comparison 3, comparing SGLT2i with GLP-1 RA add-on versus SGLT2i with DPP-4 inhibitor or sulfonylurea add-on in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3.
Measured: From index through 36 months
All-cause Mortality (Comparison 4)
All-cause mortality within 36 months in the propensity score-matched cohort for Comparison 4, comparing SGLT2i with GLP-1 RA add-on versus SGLT2i without early add-on treatment in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3.
Measured: From index through 36 months

Secondary outcomes (8)

Major Adverse Cardiovascular Events (MACE) (Comparison 1)
Major adverse cardiovascular events within 36 months in the propensity score-matched cohort for Comparison 1, comparing GLP-1 RA with SGLT2i add-on versus GLP-1 RA with DPP-4 inhibitor or sulfonylurea add-on in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3.
Measured: From index through 36 months
Major Adverse Cardiovascular Events (MACE) (Comparison 2)
Major adverse cardiovascular events within 36 months in the propensity score-matched cohort for Comparison 2, comparing GLP-1 RA with SGLT2i add-on versus GLP-1 RA without early add-on treatment in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3.
Measured: From index through 36 months
Major Adverse Cardiovascular Events (MACE) (Comparison 3)
Major adverse cardiovascular events within 36 months in the propensity score-matched cohort for Comparison 3, comparing SGLT2i with GLP-1 RA add-on versus SGLT2i with DPP-4 inhibitor or sulfonylurea add-on in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3.
Measured: From index through 36 months
Major Adverse Cardiovascular Events (MACE) (Comparison 4)
Major adverse cardiovascular events within 36 months in the propensity score-matched cohort for Comparison 4, comparing SGLT2i with GLP-1 RA add-on versus SGLT2i without early add-on treatment in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3.
Measured: From index through 36 months
Major Adverse Kidney Events (MAKE) (Comparison 1)
Major adverse kidney events within 36 months in the propensity score-matched cohort for Comparison 1, comparing GLP-1 RA with SGLT2i add-on versus GLP-1 RA with DPP-4 inhibitor or sulfonylurea add-on in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3.
Measured: From index through 36 months
Major Adverse Kidney Events (MAKE) (Comparison 2)
Major adverse kidney events within 36 months in the propensity score-matched cohort for Comparison 2, comparing GLP-1 RA with SGLT2i add-on versus GLP-1 RA without early add-on treatment in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3.
Measured: From index through 36 months
Major Adverse Kidney Events (MAKE) (Comparison 3)
Major adverse kidney events within 36 months in the propensity score-matched cohort for Comparison 3, comparing SGLT2i with GLP-1 RA add-on versus SGLT2i with DPP-4 inhibitor or sulfonylurea add-on in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3.
Measured: From index through 36 months
Major Adverse Kidney Events (MAKE) (Comparison 4)
Major adverse kidney events within 36 months in the propensity score-matched cohort for Comparison 4, comparing SGLT2i with GLP-1 RA add-on versus SGLT2i without early add-on treatment in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3.
Measured: From index through 36 months

Timeline

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

1 Jan 201731 Jan 2026

First posted12 Mar 2026
Study start1 Jan 2017
Primary completion31 Jan 2026
Study completion31 Jan 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 (50)Papers the sponsor has linked to this study.
Other trials for Cardiovascular-kidney-metabolic SyndromeStudies 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: 451,036 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07465926
Sponsor's protocol ID: CS1-25149
Other IDs: NSTC 113-2314-B-040-026-MY2, NSTC 114-2622-B-040-001, CSH-2025-C-012, CSH-2025-C-023
Acronym: GLP1-SGLT2-CKM
Status last verified: May 2026
First submitted: 8 Mar 2026
Last updated: 22 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 electronic health record data from the TriNetX US Collaborative Network. Access to individual-level data is restricted by data use agreements, institutional policies, and participant privacy protections.

Publications

American Diabetes Association Professional Practice Committee. 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes-2025. Diabetes Care. 2025 Jan 1;48(1 Suppl 1):S207-S238. doi: 10.2337/dc25-S010.
PubMed 39651970
Baker-Smith CM, Gauen AM, Petito LC, Khan SS, Allen NB. Prevalence of Cardiovascular-Kidney-Metabolic Stages in US Adolescents and Relationship to Social Determinants of Health. J Am Heart Assoc. 2025 May 20;14(10):e040269. doi: 10.1161/JAHA.124.040269. Epub 2025 May 15.
PubMed 40371589
American Diabetes Association Professional Practice Committee. 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes-2025. Diabetes Care. 2025 Jan 1;48(1 Suppl 1):S239-S251. doi: 10.2337/dc25-S011.
PubMed 39651975
Aggarwal R, Ostrominski JW, Vaduganathan M. Prevalence of Cardiovascular-Kidney-Metabolic Syndrome Stages in US Adults, 2011-2020. JAMA. 2024 Jun 4;331(21):1858-1860. doi: 10.1001/jama.2024.6892.
PubMed 38717747
Tsai MK, Kao JT, Wong CS, Liao CT, Lo WC, Chien KL, Wen CP, Wu MS, Wu MY. Cardiovascular-kidney-metabolic syndrome and all-cause and cardiovascular mortality: A retrospective cohort study. PLoS Med. 2025 Jun 26;22(6):e1004629. doi: 10.1371/journal.pmed.1004629. eCollection 2025 Jun.
PubMed 40570007
Hirohama D, Fadista J, Ha E, Liu H, Abedini A, Levinsohn J, Vassalotti A, Zeng L, Li C, Mohandes S, Vitale S, Shungin D, Nguyen T, Niewczas MA, Olsson N, McAllister FE, Karihaloo A, Susztak K. The proteogenomic landscape of the human kidney and implications for cardio-kidney-metabolic health. Nat Med. 2025 Nov;31(11):3917-3929. doi: 10.1038/s41591-025-03872-8. Epub 2025 Aug 12.
PubMed 40796935
Hernan MA, Sauer BC, Hernandez-Diaz S, Platt R, Shrier I. Specifying a target trial prevents immortal time bias and other self-inflicted injuries in observational analyses. J Clin Epidemiol. 2016 Nov;79:70-75. doi: 10.1016/j.jclinepi.2016.04.014. Epub 2016 May 27.
PubMed 27237061
Wong CK, Drucker DJ. Antiinflammatory actions of glucagon-like peptide-1-based therapies beyond metabolic benefits. J Clin Invest. 2025 Nov 3;135(21):e194751. doi: 10.1172/JCI194751. eCollection 2025 Nov 3.
PubMed 41178710
The EMPA-KIDNEY Collaborative Group; Herrington WG, Staplin N, Wanner C, Green JB, Hauske SJ, Emberson JR, Preiss D, Judge P, Mayne KJ, Ng SYA, Sammons E, Zhu D, Hill M, Stevens W, Wallendszus K, Brenner S, Cheung AK, Liu ZH, Li J, Hooi LS, Liu W, Kadowaki T, Nangaku M, Levin A, Cherney D, Maggioni AP, Pontremoli R, Deo R, Goto S, Rossello X, Tuttle KR, Steubl D, Petrini M, Massey D, Eilbracht J, Brueckmann M, Landray MJ, Baigent C, Haynes R. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2023 Jan 12;388(2):117-127. doi: 10.1056/NEJMoa2204233. Epub 2022 Nov 4.
PubMed 36331190
Verma S, Bhatta M, Davies M, Deanfield JE, Garvey WT, Jensen C, Kandler K, Kushner RF, Rubino DM, Kosiborod MN. Effects of once-weekly semaglutide 2.4 mg on C-reactive protein in adults with overweight or obesity (STEP 1, 2, and 3): Exploratory analyses of three randomised, double-blind, placebo-controlled, phase 3 trials. EClinicalMedicine. 2022 Nov 29;55:101737. doi: 10.1016/j.eclinm.2022.101737. eCollection 2023 Jan.
PubMed 36467859
Massy ZA, Drueke TB. Combination of Cardiovascular, Kidney, and Metabolic Diseases in a Syndrome Named Cardiovascular-Kidney-Metabolic, With New Risk Prediction Equations. Kidney Int Rep. 2024 Jun 6;9(9):2608-2618. doi: 10.1016/j.ekir.2024.05.033. eCollection 2024 Sep.
PubMed 39291205
Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, Nissen SE, Pocock S, Poulter NR, Ravn LS, Steinberg WM, Stockner M, Zinman B, Bergenstal RM, Buse JB; LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2016 Jul 28;375(4):311-22. doi: 10.1056/NEJMoa1603827. Epub 2016 Jun 13.
PubMed 27295427
Verma S, Sharma A, Zinman B, Ofstad AP, Fitchett D, Brueckmann M, Wanner C, Zwiener I, George JT, Inzucchi SE, Butler J, Mazer CD. Empagliflozin reduces the risk of mortality and hospitalization for heart failure across Thrombolysis In Myocardial Infarction Risk Score for Heart Failure in Diabetes categories: Post hoc analysis of the EMPA-REG OUTCOME trial. Diabetes Obes Metab. 2020 Jul;22(7):1141-1150. doi: 10.1111/dom.14015. Epub 2020 Mar 29.
PubMed 32227432
Zheng Z, Zong Y, Ma Y, Tian Y, Pang Y, Zhang C, Gao J. Glucagon-like peptide-1 receptor: mechanisms and advances in therapy. Signal Transduct Target Ther. 2024 Sep 18;9(1):234. doi: 10.1038/s41392-024-01931-z.
PubMed 39289339
Upadhyay A. SGLT2 Inhibitors and Kidney Protection: Mechanisms Beyond Tubuloglomerular Feedback. Kidney360. 2024 May 1;5(5):771-782. doi: 10.34067/KID.0000000000000425. Epub 2024 Mar 25.
PubMed 38523127

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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Study at a glance

From the registry record, last updated by the sponsor on 22 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Associations of Early Add-On GLP-1 Receptor Agonist and SGLT2 Inhibitor Therapy With Mortality and Kidney Outcomes in Adults With Obesity and Type 2 Diabetes Across Cardiovascular-Kidney-Metabolic Stages 2-3: A Target-Trial Emulation
ClinicalTrials.gov ID: NCT07465926
Acronym / sponsor ID: GLP1-SGLT2-CKM / CS1-25149
Conditions: Cardiovascular-kidney-metabolic Syndrome, Cardiovascular Disease Risk Factor, Kidney Disease, Type 2 Diabetes, Obesity & Overweight
Keywords: GLP-1 RA, SGLT2i, Target trial emulation, TriNetX, Cardiovascular-Kidney-Metabolic Syndrome, Obesity, T2D
Study type: Observational
Recruitment status: Completed
Enrolment: 451,036 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 Jan 2026 (actual)
Study completion: 31 Jan 2026 (actual)
First posted: 12 Mar 2026 (actual)
Results: Posted 22 Jun 2026

Clinical summary

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

Detailed description

Study design

Observational model: Cohort
Time perspective: Retrospective
Number of arms: 2

Arm	Type	Receives
GLP-1 RA Base Therapy	–	Drug: GLP-1 receptor agonist, Drug: SGLT2 inhibitorAdults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3 who initiated a GLP-1 receptor agonist as base therapy after a 6-month washout from GLP-1 RA, SGLT2i, DPP-4i, and sulfonylureas. Within this cohort, participants were classified by the first add-on treatment within 90 days into three mutually exclusive strategies: SGLT2i add-on, DPP-4i or sulfonylurea add-on, or no early add-on.
SGLT2i Base Therapy	–	Drug: GLP-1 receptor agonist, Drug: SGLT2 inhibitorAdults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3 who initiated an SGLT2 inhibitor as base therapy after a 6-month washout from GLP-1 RA, SGLT2i, DPP-4i, and sulfonylureas. Within this cohort, participants were classified by the first add-on treatment within 90 days into three mutually exclusive strategies: GLP-1 RA add-on, DPP-4i or sulfonylurea add-on, or no early add-on.

Who may qualify

Ages: 20 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
Study population: Adults (≥20 years) with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3 identified from routinely collected electronic health record data in the TriNetX US Collaborative Network. Participants initiated a GLP-1 receptor agonist or an SGLT2 inhibitor and were classified according to early add-on treatment strategies.

Key inclusion criteria (6 listed)

Adults aged 20 years or older.
Obesity, defined by body mass index (BMI) 27 kg/m2 or greater.
Type 2 diabetes mellitus, defined using electronic health record data, including diagnosis codes and/or hemoglobin A1c 6.5% or greater.
Met cardiovascular-kidney-metabolic (CKM) stage 2-3 criteria at baseline.
Initiated a GLP-1 receptor agonist or an SGLT2 inhibitor as background therapy.

Key exclusion criteria (6 listed)

Prior use of GLP-1 receptor agonists, SGLT2 inhibitors, DPP-4 inhibitors, or sulfonylureas within 6 months before cohort entry.
Major cardiovascular disease or revascularization within 12 months before cohort entry.
Advanced kidney disease within 12 months before cohort entry, including end-stage kidney disease, dialysis, or estimated glomerular filtration rate less than 15 mL/min/1.73 m2.
Major cardiovascular or renal events within 6 months before index.
Any history of non-type 2 diabetes, HIV infection, bariatric surgery, or 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.

Interventions

Intervention	Type	Arms
GLP-1 receptor agonistUse of a glucagon-like peptide-1 receptor agonist as background therapy or add-on therapy in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3.	Drug	GLP-1 RA Base Therapy, SGLT2i Base Therapy
SGLT2 inhibitorUse of a sodium-glucose cotransporter-2 inhibitor as background therapy or add-on therapy in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3.	Drug	GLP-1 RA Base Therapy, SGLT2i Base Therapy

Primary outcome

All-cause Mortality (Comparison 1)
Time frame: From index through 36 months
All-cause mortality within 36 months in the propensity score-matched cohort for Comparison 1, comparing GLP-1 RA with SGLT2i add-on versus GLP-1 RA with DPP-4 inhibitor or sulfonylurea add-on in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3.
All-cause Mortality (Comparison 2)
Time frame: From index through 36 months
All-cause mortality within 36 months in the propensity score-matched cohort for Comparison 2, comparing GLP-1 RA with SGLT2i add-on versus GLP-1 RA without early add-on treatment in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3.
All-cause Mortality (Comparison 3)
Time frame: From index through 36 months
All-cause mortality within 36 months in the propensity score-matched cohort for Comparison 3, comparing SGLT2i with GLP-1 RA add-on versus SGLT2i with DPP-4 inhibitor or sulfonylurea add-on in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3.
All-cause Mortality (Comparison 4)
Time frame: From index through 36 months
All-cause mortality within 36 months in the propensity score-matched cohort for Comparison 4, comparing SGLT2i with GLP-1 RA add-on versus SGLT2i without early add-on treatment in adults with obesity, type 2 diabetes, and cardiovascular-kidney-metabolic stage 2-3.

8 secondary outcomes

Major Adverse Cardiovascular Events (MACE) (Comparison 1)
Time frame: From index through 36 months
Major Adverse Cardiovascular Events (MACE) (Comparison 2)
Time frame: From index through 36 months
Major Adverse Cardiovascular Events (MACE) (Comparison 3)
Time frame: From index through 36 months
Major Adverse Cardiovascular Events (MACE) (Comparison 4)
Time frame: From index through 36 months
Major Adverse Kidney Events (MAKE) (Comparison 1)
Time frame: From index through 36 months
Major Adverse Kidney Events (MAKE) (Comparison 2)
Time frame: From index through 36 months
Major Adverse Kidney Events (MAKE) (Comparison 3)
Time frame: From index through 36 months
Major Adverse Kidney Events (MAKE) (Comparison 4)
Time frame: From index through 36 months

Results and safety

Results posted to the registry on 22 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 Base Therapy	278,273	278,273
SGLT2i Base Therapy	172,763	172,763

Primary outcome: All-cause Mortality (Comparison 1)

Time frame: From index through 36 months. Number. Unit: participants with event

Measure	GLP-1 RA With SGLT2i Add-On (Comparison 1) n = 16864	GLP-1 RA With DPP-4i/SU Add-On (Comparison 1) n = 16827
Value	291	444

Population analysed: Participants analyzed for each outcome were members of the propensity score-matched cohort who had sufficient follow-up and available source data to assess that specific outcome during the 36-month observation period. Therefore, the number analyzed may be smaller than the corresponding matched cohort size shown in Participant Flow, and may also differ across outcome measures because each outcome was assessed in an outcome-specific analysis population.

Primary outcome: All-cause Mortality (Comparison 2)

Time frame: From index through 36 months. Number. Unit: participants with event

Measure	GLP-1 RA With SGLT2i Add-On (Comparison 2) n = 39552	GLP-1 RA Only (No Early Add-On) (Comparison 2) n = 39518
Value	674	877

Primary outcome: All-cause Mortality (Comparison 3)

Time frame: From index through 36 months. Number. Unit: participants with event

Measure	SGLT2i With GLP-1 RA Add-On (Comparison 3) n = 18850	SGLT2i With DPP-4i/SU Add-On (Comparison 3) n = 18941
Value	352	562

Primary outcome: All-cause Mortality (Comparison 4)

Time frame: From index through 36 months. Number. Unit: participants with event

Measure	SGLT2i With GLP-1 RA Add-On (Comparison 4) n = 34963	SGLT2i Only (No Early Add-On) (Comparison 4) n = 34987
Value	593	770

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: From index date through 36 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)	754 of 16,796 (4.5%)	0 of 0	291 of 16,864
GLP-1 RA With DPP-4i/SU Add-On (Comparison 1)	983 of 16,734 (5.9%)	0 of 0	444 of 16,827
GLP-1 RA With SGLT2i Add-On (Comparison 2)	1,862 of 39,392 (4.7%)	0 of 0	674 of 39,552
GLP-1 RA Only (No Early Add-On) (Comparison 2)	2,073 of 39,243 (5.3%)	0 of 0	877 of 39,518
SGLT2i With GLP-1 RA Add-On (Comparison 3)	854 of 18,771 (4.5%)	0 of 0	352 of 18,850
SGLT2i With DPP-4i/SU Add-On (Comparison 3)	1,223 of 18,868 (6.5%)	0 of 0	562 of 18,941
SGLT2i With GLP-1 RA Add-On (Comparison 4)	1,495 of 34,819 (4.3%)	0 of 0	593 of 34,963
SGLT2i Only (No Early Add-On) (Comparison 4)	1,727 of 34,827 (5%)	0 of 0	770 of 34,987

Limitations and caveats (from the sponsor): This retrospective observational target-trial emulation is subject to residual confounding, misclassification, and missing or incomplete electronic health record data. Treatment strategies were not randomly assigned, and matching was performed separately for each pairwise comparison.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 39651970American Diabetes Association Professional Practice Committee. 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes-2025. Diabetes Care. 2025 Jan 1;48(1 Suppl 1):S207-S238. doi: 10.2337/dc25-S010.
Background: PubMed 40371589Baker-Smith CM, Gauen AM, Petito LC, Khan SS, Allen NB. Prevalence of Cardiovascular-Kidney-Metabolic Stages in US Adolescents and Relationship to Social Determinants of Health. J Am Heart Assoc. 2025 May 20;14(10):e040269. doi: 10.1161/JAHA.124.040269. Epub 2025 May 15.
Background: PubMed 39651975American Diabetes Association Professional Practice Committee. 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes-2025. Diabetes Care. 2025 Jan 1;48(1 Suppl 1):S239-S251. doi: 10.2337/dc25-S011.
Background: PubMed 38717747Aggarwal R, Ostrominski JW, Vaduganathan M. Prevalence of Cardiovascular-Kidney-Metabolic Syndrome Stages in US Adults, 2011-2020. JAMA. 2024 Jun 4;331(21):1858-1860. doi: 10.1001/jama.2024.6892.
Background: PubMed 40570007Tsai MK, Kao JT, Wong CS, Liao CT, Lo WC, Chien KL, Wen CP, Wu MS, Wu MY. Cardiovascular-kidney-metabolic syndrome and all-cause and cardiovascular mortality: A retrospective cohort study. PLoS Med. 2025 Jun 26;22(6):e1004629. doi: 10.1371/journal.pmed.1004629. eCollection 2025 Jun.
Background: PubMed 40796935Hirohama D, Fadista J, Ha E, Liu H, Abedini A, Levinsohn J, Vassalotti A, Zeng L, Li C, Mohandes S, Vitale S, Shungin D, Nguyen T, Niewczas MA, Olsson N, McAllister FE, Karihaloo A, Susztak K. The proteogenomic landscape of the human kidney and implications for cardio-kidney-metabolic health. Nat Med. 2025 Nov;31(11):3917-3929. doi: 10.1038/s41591-025-03872-8. Epub 2025 Aug 12.
Background: PubMed 27237061Hernan MA, Sauer BC, Hernandez-Diaz S, Platt R, Shrier I. Specifying a target trial prevents immortal time bias and other self-inflicted injuries in observational analyses. J Clin Epidemiol. 2016 Nov;79:70-75. doi: 10.1016/j.jclinepi.2016.04.014. Epub 2016 May 27.
Background: PubMed 41178710Wong CK, Drucker DJ. Antiinflammatory actions of glucagon-like peptide-1-based therapies beyond metabolic benefits. J Clin Invest. 2025 Nov 3;135(21):e194751. doi: 10.1172/JCI194751. eCollection 2025 Nov 3.
Background: PubMed 36331190The EMPA-KIDNEY Collaborative Group; Herrington WG, Staplin N, Wanner C, Green JB, Hauske SJ, Emberson JR, Preiss D, Judge P, Mayne KJ, Ng SYA, Sammons E, Zhu D, Hill M, Stevens W, Wallendszus K, Brenner S, Cheung AK, Liu ZH, Li J, Hooi LS, Liu W, Kadowaki T, Nangaku M, Levin A, Cherney D, Maggioni AP, Pontremoli R, Deo R, Goto S, Rossello X, Tuttle KR, Steubl D, Petrini M, Massey D, Eilbracht J, Brueckmann M, Landray MJ, Baigent C, Haynes R. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2023 Jan 12;388(2):117-127. doi: 10.1056/NEJMoa2204233. Epub 2022 Nov 4.
Background: PubMed 36467859Verma S, Bhatta M, Davies M, Deanfield JE, Garvey WT, Jensen C, Kandler K, Kushner RF, Rubino DM, Kosiborod MN. Effects of once-weekly semaglutide 2.4 mg on C-reactive protein in adults with overweight or obesity (STEP 1, 2, and 3): Exploratory analyses of three randomised, double-blind, placebo-controlled, phase 3 trials. EClinicalMedicine. 2022 Nov 29;55:101737. doi: 10.1016/j.eclinm.2022.101737. eCollection 2023 Jan.
Background: PubMed 39291205Massy ZA, Drueke TB. Combination of Cardiovascular, Kidney, and Metabolic Diseases in a Syndrome Named Cardiovascular-Kidney-Metabolic, With New Risk Prediction Equations. Kidney Int Rep. 2024 Jun 6;9(9):2608-2618. doi: 10.1016/j.ekir.2024.05.033. eCollection 2024 Sep.
Background: PubMed 27295427Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, Nissen SE, Pocock S, Poulter NR, Ravn LS, Steinberg WM, Stockner M, Zinman B, Bergenstal RM, Buse JB; LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2016 Jul 28;375(4):311-22. doi: 10.1056/NEJMoa1603827. Epub 2016 Jun 13.
Individual participant dataSharing planned: No. Individual participant data will not be shared. This retrospective observational study uses electronic health record data from the TriNetX US Collaborative Network. Access to individual-level data is restricted by data use agreements, institutional policies, and participant privacy protections.

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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 Cardiovascular-kidney-metabolic Syndrome and Cardiovascular Disease Risk Factor, 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 6 inclusion and 6 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 22 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 22 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 index through 36 months). 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 NCT07465926, which also lists 50 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 22 Jun 2026.