Skip to main content
OpenTrials
Completed

NCT Number: NCT07465926

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Cardiovascular-kidney-metabolic Syndrome Body Weight Cardiovascular Disease Risk Factor Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Glucose Metabolism Disorders Kidney Disease Kidney Diseases Male Urogenital Diseases Metabolic Diseases Nutrition Disorders Nutritional and Metabolic Diseases Obesity Obesity & Overweight Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms Type 2 Diabetes Urogenital Diseases Urologic Diseases

Age range

20 year and older

Sex eligibility

All sexes

Study type

Observational

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.

Treatment and study plan

GLP-1 receptor agonist

Drug

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 inhibitor

Drug

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.

Primary outcomes

  1. 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.

  2. 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.

  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.

  4. 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.

Secondary outcomes

  1. Major Adverse Cardiovascular Events (MACE) (Comparison 1)

    Time frame: From index through 36 months

    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.

  2. Major Adverse Cardiovascular Events (MACE) (Comparison 2)

    Time frame: From index through 36 months

    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.

  3. Major Adverse Cardiovascular Events (MACE) (Comparison 3)

    Time frame: From index through 36 months

    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.

  4. Major Adverse Cardiovascular Events (MACE) (Comparison 4)

    Time frame: From index through 36 months

    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.

  5. Major Adverse Kidney Events (MAKE) (Comparison 1)

    Time frame: From index through 36 months

    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.

  6. Major Adverse Kidney Events (MAKE) (Comparison 2)

    Time frame: From index through 36 months

    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.

  7. Major Adverse Kidney Events (MAKE) (Comparison 3)

    Time frame: From index through 36 months

    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.

  8. Major Adverse Kidney Events (MAKE) (Comparison 4)

    Time frame: From index through 36 months

    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.

Sponsors and collaborators

Lead sponsor

Chung Shan Medical University

Other

Collaborators

  • National Science and Technology Council, Taiwan

Registry information

Official study 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

Acronym: GLP1-SGLT2-CKM

Important dates

Study start
2017
Primary completion
2026
Study completion
2026
First posted
Mar 12, 2026
Registry last updated
Jun 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.