Comparative Effectiveness of Tirzepatide Versus Semaglutide in Individuals With Heart Failure With Preserved Ejection Fraction

NCT06914141 | Completed FDA Drug

• 1 other identifier: 2018P002966-DUP-TIRZSEMA
• Study Type: observational
• Target: 28,118
• Locations: 1 country
• Sites: 1

Brief Summary

Investigators are building an empirical evidence base for real-world data through large-scale emulation of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.

Conditions

Diabetes Mellitus, Type 2; HFpEF - Heart Failure With Preserved Ejection Fraction

Outcome Measures

Primary Outcomes (1)

• Composite of all-cause mortality or heart failure hospitalization

  To evaluate the comparative effect of tirzepatide vs semaglutide on all-cause mortality or heart failure hospitalization in patients with heart failure with preserved ejection fraction.

  Through study completion (1 day after cohort entry date until the first of outcome or censoring)

Secondary Outcomes (8)

• Composite of all-cause mortality or all-cause mortality or a worsening heart failure event (exacerbated symptoms of heart failure resulting in hospitalization, intravenous diuretic therapy in an urgent care setting).

  Through study completion (1 day after cohort entry date until the first of outcome or censoring)

• Worsening heart failure event (exacerbated symptoms of heart failure resulting in hospitalization or intravenous diuretic therapy in an urgent care setting).

  Through study completion (1 day after cohort entry date until the first of outcome or censoring)

• Intravenous diuretic therapy in an urgent care setting

  Through study completion (1 day after cohort entry date until the first of outcome or censoring)

• Hospitalization for heart failure

  Through study completion (1 day after cohort entry date until the first of outcome or censoring)

• All-cause mortality

  Through study completion (1 day after cohort entry date until the first of outcome or censoring)

Other Outcomes (2)

• Hernia

  Through study completion (1 day after cohort entry date until the first of outcome or censoring)

• Lumbar radiculopathy

  Through study completion (1 day after cohort entry date until the first of outcome or censoring)

Study Arms (2)

Tirzepatide

New use of tirzepatide dispensing claim is used as the exposure.

Drug: Tirzepatide

Semaglutide

New use of semaglutide dispensing claim is used as the reference.

Drug: Semaglutide

Interventions

Semaglutide DRUG

New use of semaglutide dispensing claim is used as the reference.

Semaglutide

Tirzepatide DRUG

New use of tirzepatide dispensing claim is used as the exposure.

Tirzepatide

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

The study population includes individuals aged 40 years or older with heart failure with preserved ejection fraction.

You may qualify if:

• Heart failure
• BMI \> 27.0 kg/m2
• History of type 2 diabetes mellitus
• LVEF ≥ 45%
• ≥ 18 years old, male or female sex

You may not qualify if:

• Prior treatment with any GLP-1-RA
• History of type 1 diabetes mellitus
• End-stage renal disease or chronic or intermittent haemodialysis or peritoneal dialysis
• History of bariatric surgery
• History of nursing home admission
• Pregnant female or breastfeeding
• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy
• Treatment with continuous subcutaneous insulin infusion
• Multiple endocrine neoplasia type 2 or medullary thyroid carcinoma
• Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy (other than basal- or squamous-cell skin cancer, in situ carcinoma of the cervix, or in situ prostate cancer) for less than 5 years

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02120, United States

Location

Related Publications (1)

• Kruger N, Schneeweiss S, Fuse K, Matseyko S, Sreedhara SK, Hahn G, Schunkert H, Wang SV. Semaglutide and Tirzepatide in Patients With Heart Failure With Preserved Ejection Fraction. JAMA. 2025 Oct 14;334(14):1255-1266. doi: 10.1001/jama.2025.14092.

  PMID: 40886075 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Tirzepatide; semaglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Study Officials

• Shirley Wang, PhD, ScM

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

• Nils Krüger, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: March 31, 2025
• First Posted: April 6, 2025
• Study Start: January 14, 2025
• Primary Completion: June 1, 2025
• Study Completion: June 1, 2025
• Last Updated: January 30, 2026

Record last verified: 2025-05

Locations

US (1)