GLP-1/GIP Receptor Agonists in Obesity-Related HFpEF: The GLIDE-HF Registry

NCT07787936 | Not Yet Recruiting

• 2 other identifiers: GLIDE-HF-MCZ-2026-01Ethics
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

GLIDE-HF is a prospective, single-center, non-interventional observational cohort registry conducted within routine outpatient heart failure care at a cardiology clinic in Poland. It enrolls patients with obesity-related heart failure with preserved ejection fraction (HFpEF), defined by chronic heart failure symptoms or exertional dyspnea, body mass index at least 30 kg/m2, left ventricular ejection fraction at least 50%, and objective evidence of HFpEF using contemporary diagnostic scores (H2FPEF and HFA-PEFF), without a dominant alternative cause of dyspnea. The registry's guiding principle is that all eligible obesity-related HFpEF patients are enrolled regardless of their treatment. Therapy with a glucagon-like peptide-1 (GLP-1) receptor agonist or a dual GLP-1/GIP receptor agonist (for example semaglutide, tirzepatide, liraglutide, dulaglutide, or others) is an observed exposure, not an assigned intervention. All decisions about initiating, selecting, dosing, or modifying such therapy are made solely by the treating physician according to clinical, regulatory, and reimbursement indications, as part of standard care and independently of the registry. The protocol does not propose, allocate, or modify any pharmacological treatment, does not randomize, and does not create a protocol-defined control group. Patients not receiving such therapy serve as a naturally occurring observational comparator. The scientific value of GLIDE-HF lies in deep mechanistic phenotyping rarely available in large-scale registries. The core assessment tool is serial exercise (stress) echocardiography, which allows direct evaluation of diastolic reserve during exercise, an abnormality that may be absent at rest and revealed only under load. This is complemented by lung ultrasound for pulmonary congestion (B-lines), left atrial and right ventricular strain analysis, a full iron and hepcidin panel, right ventricular-pulmonary artery coupling assessment, cardiac and congestion biomarkers (NT-proBNP, CA-125), quality of life (Kansas City Cardiomyopathy Questionnaire), and functional capacity (6-minute walk test). The identical assessment panel is applied to all enrolled patients regardless of treatment status, ensuring comparability between treated and untreated patients. Observation is embedded in the routine outpatient visit schedule, with assessment points at baseline and at 12, 24, and 52 weeks, and the possibility of continued follow-up. The registry characterizes trajectories of exercise diastolic reserve and accompanying mechanistic and clinical parameters over time in treated patients (primary axis), and explores comparisons between treated and untreated patients (secondary axis), with a methodological aim of assessing the feasibility of reliable serial exercise echocardiography and lung ultrasound in an unselected, real-world obesity-related HFpEF population, in whom obesity substantially complicates imaging. The registry is descriptive and hypothesis-generating. Because of its observational design, all analyses relating to treatment effect are descriptive only and cannot be interpreted as evidence of a causal drug effect, given the absence of randomization, possible regression to the mean, and confounding by indication. Target enrollment is at least 150 patients, recruited continuously from January 2027. GLIDE-HF is a non-commercial study conducted under bioethics committee opinion and applicable data protection law.

Conditions

Heart Failure With Preserved Ejection Fraction; Obesity; Diastolic Heart Failure; Pulmonary Hypertension; Iron Deficiency

Keywords

HFpEF; Obesity; GLP-1 receptor agonist; Semaglutide; Tirzepatide; stress echocardiography; Lung ultrasound

Outcome Measures

Primary Outcomes (1)

• Trajectory of exercise E/e' over time in GLP-1/GIP-exposed patients

  Change over time in the highest interpretable exercise (stress) echocardiographic average E/e' ratio, a non-invasive estimate of left ventricular filling pressure during exercise, in the GLP-1/GIP receptor agonist-exposed cohort. The highest interpretable value is selected per the protocol hierarchy (peak \> 40 W \> 20 W). Reported as mean change from baseline with 95% confidence intervals from a linear mixed model accounting for actual time since baseline; descriptive and hypothesis-generating, not a confirmatory test of treatment effect. Unit: ratio (dimensionless).

  Baseline, 12, 24, and 52 weeks

Secondary Outcomes (12)

• Trajectory of peak tricuspid regurgitation velocity

  Baseline, 12, 24, and 52 weeks

• Trajectory of LVOT VTI reserve

  Baseline, 12, 24, and 52 weeks

• Trajectory of post-exercise lung ultrasound B-line count

  Baseline, 12, 24, and 52 weeks

• Trajectory of KCCQ Clinical Summary Score

  Baseline, 12, 24, and 52 weeks

• Trajectory of NT-proBNP

  Baseline, 12, 24, and 52 weeks

Other Outcomes (1)

• Feasibility of serial exercise echocardiography and lung ultrasound

  Baseline, 12, 24, and 52 weeks

Study Arms (2)

Exposed: GLP-1/GIP receptor agonist

Patients with obesity-related HFpEF receiving a GLP-1 or dual GLP-1/GIP receptor agonist (e.g., semaglutide, tirzepatide, liraglutide, dulaglutide, or others) prescribed by the treating physician as routine care per the Summary of Product Characteristics. Therapy is an observed exposure, not assigned by protocol. Includes patients newly initiating therapy at or after enrollment (baseline at treatment start; core trajectory cohort) and patients whose therapy began before enrollment (baseline at enrollment; analyzed separately). Molecule, indication, dose, escalation, and any discontinuation are documented but not determined by the registry.

Drug: GLP-1 / GIP receptor agonist

Unexposed: observational comparator

Patients with obesity-related HFpEF not receiving a GLP-1/GIP receptor agonist, forming a naturally occurring observational comparator rather than a protocol-assigned control arm. Reason for non-treatment is categorized: economic or access reasons only (preferred primary comparator, most clinically similar to treated patients), clinical contraindication or intolerance, or patient preference. Exposure status may change over time; the direction and date of any change are recorded to enable time-varying exposure analyses.

Interventions

GLP-1 / GIP receptor agonist DRUG

Observed exposure, not assigned by the registry. GLP-1 or dual GLP-1/GIP receptor agonist (semaglutide, tirzepatide, liraglutide, dulaglutide, or others) prescribed by the treating physician as routine clinical care per the Summary of Product Characteristics and reimbursement rules. The registry documents molecule, dose, escalation, start date, modifications, discontinuations, tolerability, and adverse events, but does not propose, allocate, or modify treatment.

Exposed: GLP-1/GIP receptor agonist

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

Unselected patients with obesity-related HFpEF managed in a heart failure and cardiology outpatient clinic, enrolled regardless of whether they receive GLP-1/GIP receptor agonist therapy. Obesity-related HFpEF is defined by chronic heart failure symptoms or exertional dyspnea, BMI at least 30 kg/m2, LVEF at least 50%, and objective evidence of HFpEF (no low-probability result on either the H2FPEF or HFA-PEFF score), without a dominant alternative cause of dyspnea.

You may qualify if:

• Age 18 years or older Body mass index (BMI) 30 kg/m2 or greater Symptomatic exertional dyspnea, fatigue, or reduced exercise tolerance Left ventricular ejection fraction 50% or greater Probable or established HFpEF per the diagnostic score algorithm (no low-probability result on either the H2FPEF or HFA-PEFF score) Able to perform semi-supine bicycle exercise echocardiography Written informed consent for registry participation and data processing

You may not qualify if:

• Significant valvular heart disease Cardiomyopathy other than the typical HFpEF phenotype (suspected amyloidosis, restrictive or hypertrophic cardiomyopathy as the primary problem) Recent acute decompensated heart failure or recent hospitalization for heart failure Unstable coronary artery disease Severe pulmonary disease as the primary cause of dyspnea Severe anemia or another systemic cause of exercise limitation Inability to safely perform an exercise test Very poor echocardiographic window precluding any analysis Active malignancy or gynecological condition that may substantially affect CA-125 (diagnosed endometriosis, pelvic inflammatory disease, suspected ovarian tumor, significant non-cardiac ascites) Absence of consent for registry participation and data processing

Sponsors & Collaborators

• Miedziowe Centrum Zdrowia SA: lead

Study Sites (1)

Klinika Kardiologii, Miedziowe Centrum Zdrowia SA

Lubin, Lower Silesian Voivodeship, 59-300, Poland

Location

MeSH Terms

Conditions

Obesity; Heart Failure, Diastolic; Hypertension, Pulmonary; Iron Deficiencies

Interventions

Glucagon-Like Peptide 1

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Heart Failure; Heart Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Iron Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Central Study Contacts

Szymon Urban, MD, PhD

CONTACT

+48696489058; surban@mcz.pl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 52 Weeks
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2026
• First Posted: August 26, 2026
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): January 1, 2031
• Study Completion (Estimated): January 1, 2033
• Last Updated: August 26, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1)