Heart Failure With Reduced Ejection FractionPhase 2/3FIT-HFNCT06423599
Effect of Weight Loss on Physical and Cardiac Performance in People With Obesity and Heart Failure
A Phase 2/3 study testing Semaglutide Injectable Product and Calorie-restricted diet in people with Heart Failure With Reduced Ejection Fraction and Obesity, run by Jens D Hove, MD,PHD at 1 site in Denmark.
Trial summary
The benefit of weight loss in patients with obesity and heart failure with reduced ejection fraction (HFrEF) is controversial. Semaglutide has shown cardiovascular (CV) risk-reduction and impact on CV risk factors including overweight, dysglycaemia and hypertension in subjects with type 2 diabetes (T2D). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure With Reduced Ejection Fraction, Obesity, Weight Loss
- What is being tested?
- Semaglutide Injectable Product and Calorie-restricted diet
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteDenmark
- Study dates
- 30 Apr 2024to 30 Dec 2027
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
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
Who may be able to join
- Male or female, age ≥ 18 years at the time of signing informed consent
- Body mass index (BMI) ≥ 30 kg/m2
- Heart failure with New York Heart Association (NYHA)-class 1-3 and reduced ejection fraction (EF≤40%) established by either:
- echocardiography AND/OR
- cardiac magnetic resonance
- On stable optimal medical heart failure therapy for at least 4 weeks
Who cannot join
- Cardiovascular-related:
- Any of the following: myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within the past 6 months prior to the day of screening
- Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
- Transient heart failure related to reversible mechanisms like tachycardia, sepsis, etc.
- Glycaemia-related:
- Type 1 diabetes
Show all 15Show fewer
- Treatment with any Glucagon-Like Peptide-1 (GLP-1) agonists within 90 days prior to the day of screening
- Type 2 diabetes requiring other pharmacotherapy than metformin and Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors
- General safety:
- Pregnancy or planned pregnancy
- History or presence of chronic pancreatitis
- Presence of acute pancreatitis within the past 180 days prior to the day of screening
- Kidney disease with eGFR < 35ml/min
- Presence or history of malignant neoplasms within the past 5 years prior to the day of screening (Basal and squamous cell skin cancer and any carcinoma in-situ are allowed)
- Known or suspected hypersensitivity to trial product(s) or related products
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark1 site, 1 recruiting
- Recruiting
Amager and Hvidovre Hospital University of Copenhagen
Copenhagen, DK-2650
Jens D Hove, MD, PhD, +4538623218, jens.dahlgaard.hove@regionh.dk
Mohammed El-Sheikh, MD, +4552309685, mohammed.el-sheikh.02@regionh.dk
About this study
The benefit of weight loss in patients with obesity and heart failure with reduced ejection fraction (HFrEF) is controversial. Semaglutide has shown cardiovascular (CV) risk-reduction and impact on CV risk factors including overweight, dysglycaemia and hypertension in subjects with type 2 diabetes (T2D). The STEP-HFpEF (Semaglutide Treatment Effect in People With Obesity and HFpEF) recently demonstrated, at 1-year, to not only reduce weight considerably, but also significantly improve health-related quality of life, functional status scores and 6-min walk distance in patients with heart failure with preserved ejection fraction (HFpEF). Also, the recently concluded SELECT trial was the first CV outcome trial with semaglutide in patients with overweight or obesity and established CV disease, including heart failure (but no T2D). Semaglutide demonstrated a 20% reduction in MACE, defined as the composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke.
These landmark findings have important implications for clinicians -as they mean that weight loss and/or semaglutide as anti-obesity pharmacotherapy could be a treatment strategy for secondary prevention of CV disease in patients with overweight or obesity.
Read more
It is, however, unknown whether weight loss with either calorie-restricted diet or semaglutide has beneficial effects in obese subjects with heart failure and reduced ejection fraction. Also it is unclear whether semaglutide has cardiovascular benefits irrespective of starting weight and amount of weight loss.
Purpose: The study aims to investigate whether weight loss treatment with semaglutide is superior to weight loss with calorie-restricted diet in improving peak oxygen uptake in patients with obesity and heart failure with reduced ejection fraction.
Read the detailed description
Background: The prevalence of overweight and obesity has reached pandemic proportions. Obesity is known to increase the risk for Type 2 diabetes and hypertension, as well as the risk for overt cardiovascular (CV) disease, including myocardial infarction, heart failure, and stroke. The rising prevalence of obesity may counteract the recent advances in primary and secondary prevention of CV disease. Overweight and obesity are common in patients with CV disease; however, cardiologists face several challenges in managing body weight in this population. Many may not consider obesity as a therapeutic target probably because there were no previous highly effective and safe pharmacologic interventions to consider. In addition, they may not have the expertise or resources to implement lifestyle interventions and may have limited familiarity with obesity pharmacotherapy. Moreover, the long-term CV effects of obesity pharmacotherapy remain uncertain due to limited CV outcome data with weight loss as the primary intervention. Although current CV guidelines recognize the importance of weight loss, they primarily focus on lifestyle modifications, with fewer details on strategies to utilize obesity pharmacotherapy and surgery. However, the recent 2022 American Diabetes Association/European Association for the Study of Diabetes consensus on the management of Type 2 diabetes has moved up weight management to the front of the treatment algorithm, by prioritizing the use of pharmacologic interventions such as glucagon-like peptide-1 receptor agonists and dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists, which have potent weight-lowering effects, in addition to glucose-lowering effects.
Hypothesis: The investigators hypothesise that weight loss treatment with semaglutide is superior to weight loss with state-of-the-art calorie-restricted diet in improving the peak oxygen uptake (ml/min/kg) after 52 weeks as a marker of physical performance (and with prognostic implications) in patients with obesity and heart failure with reduced ejection fraction.
Design: This is a investigator-initiated, parallel-group, 2-arm assessor-blinded, open-label, randomised, controlled trial (RCT) comparing the effect of weight loss using low-calorie replacement diet to weight loss using semaglutide in obese patients with heart failure with reduced ejection fraction. Subjects will be randomised in a 1:1 ratio to receive either low-calorie replacement diet or semaglutide.The subjects wil be followed for 52 weeks during the intervention period. The patients will be examined at 16 weeks (where the weight loss is anticipated to be approximately equal in the two groups) and after 52 weeks.
Primary, secondary and exploratory objectives are listed below. The exploratory objectives are mostly embedded mechanistic studies of an exploratory nature and therefore hypothesis-generating in the RCT.
Intervention: Subjects will be treated with semaglutide once weekly or a weight loss intervention consisting of a calorie-restricted diet and dietary advice on top of standard of care, which covers management of heart failure medication, CV risk factors and healthy lifestyle counselling.
- Being tested
- Semaglutide Injectable Product, Calorie-restricted diet
- Medical subject headings
- Obesity, Weight Loss
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Semaglutide Injectable ProductDrug
Weight loss using Semaglutide
Calorie-restricted dietDietary supplement
Weight loss by calorie-restricted diet program followed by a weight loss maintenance follow-up program
| Study group | Role | What they receive |
|---|---|---|
| Semaglutide intervention group | Experimental | Dose-escalation of semaglutide will take place during the first 16 weeks after randomisation (week 0). Patients will start at the 0.25 mg once-weekly dose and follow dose-escalation schedule (0.25, 0.5, 1.0, 1.7 and 2.4 mg). For all subjects we aim at reaching the recommended target dose of 2.4 mg semaglutide once weekly for the rest of the period of total 52 weeks. Receives: Drug: Semaglutide Injectable Product |
| Calorie-restricted diet intervention group | Active comparator | In short, the weight loss program in the calorie-restricted diet group consists of 3 phases after randomisation (week 0). An initial weight loss phase of 8 weeks with 800 calories/day, a food re-introduction phase for 8 weeks and a weight loss maintenance phase for the rest of the period of total 52 weeks. Receives: Dietary Supplement: Calorie-restricted diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak oxygen uptake
To examine the effect of weight loss on mean change in peak oxygen uptake at 52 weeks between semaglutide and calorie-restricted group compared to baseline (Measured in ml O2/(kg x min))
Measured: The patients will be examined after 0, 16 and 52 weeks
Secondary outcomes (4)
The Clinical Summary Score of the Kansas City Cardiomyopathy Questionnaire (KCCQ-CSS)
To compare the effect of weight loss on the mean change
Measured: The patients will be examined after 0, 16 and 52 weeks.
6-min walk distance (6MWD)
To compare the effect of weight loss on the mean change
Measured: The patients will be examined after 0, 16 and 52 weeks
End-systolic volume of the left ventricle assessed by Cardiac MRI
To compare the effect of weight loss on the mean change
Measured: The patients will be examined after 0, 16 and 52 weeks
N-terminal pro-B-type natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) change
To compare the effect of weight loss on the mean change
Measured: The patients will be examined after 0, 16 and 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2024
- Study start30 Apr 2024
- Primary completion30 Dec 2027 (estimated)
- Study completion30 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure With Reduced Ejection FractionStudies 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
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a investigator-initiated, parallel-group, 2-arm assessor-blinded, open-label, randomised, clinical trial
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jens D Hove, MD,PHD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jens D Hove, MD,PHD, Hvidovre University Hospital
- Investigators
- Jens D Hove, Principal investigator, Amager-Hvidovre Universitetshospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06423599
- Sponsor's protocol ID
- U1111-1298-6418
- Other IDs
- 2023-503753-35-01, 2023
- Acronym
- FIT-HF
- Status last verified
- Jun 2026
- First submitted
- 16 May 2024
- Last updated
- 23 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Weight Loss on Physical and Cardiac Performance in People With Obesity and Heart Failure
- ClinicalTrials.gov ID
- NCT06423599
- Acronym / sponsor ID
- FIT-HF / U1111-1298-6418
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Jens D Hove, MD,PHDUniversity, hospital or other
- Study start
- 30 Apr 2024 (actual)
- Primary completion
- 30 Dec 2027 (estimated)
- Study completion
- 30 Dec 2027 (estimated)
- First posted
- 21 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The benefit of weight loss in patients with obesity and heart failure with reduced ejection fraction (HFrEF) is controversial. Semaglutide has shown cardiovascular (CV) risk-reduction and impact on CV risk factors including overweight, dysglycaemia and hypertension in subjects with type 2 diabetes (T2D). The STEP-HFpEF (Semaglutide Treatment Effect in People With Obesity and HFpEF) recently demonstrated, at 1-year, to not only reduce weight considerably, but also significantly improve health-related quality of life, functional status scores and 6-min walk distance in patients with heart failure with preserved ejection fraction (HFpEF). Also, the recently concluded SELECT trial was the first CV outcome trial with semaglutide in patients with overweight or obesity and established CV disease, including heart failure (but no T2D). Semaglutide demonstrated a 20% reduction in MACE, defined as the composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke.
These landmark findings have important implications for clinicians -as they mean that weight loss and/or semaglutide as anti-obesity pharmacotherapy could be a treatment strategy for secondary prevention of CV disease in patients with overweight or obesity.
It is, however, unknown whether weight loss with either calorie-restricted diet or semaglutide has beneficial effects in obese subjects with heart failure and reduced ejection fraction. Also it is unclear whether semaglutide has cardiovascular benefits irrespective of starting weight and amount of weight loss.
Purpose: The study aims to investigate whether weight loss treatment with semaglutide is superior to weight loss with calorie-restricted diet in improving peak oxygen uptake in patients with obesity and heart failure with reduced ejection fraction.
Detailed description
Background: The prevalence of overweight and obesity has reached pandemic proportions. Obesity is known to increase the risk for Type 2 diabetes and hypertension, as well as the risk for overt cardiovascular (CV) disease, including myocardial infarction, heart failure, and stroke. The rising prevalence of obesity may counteract the recent advances in primary and secondary prevention of CV disease. Overweight and obesity are common in patients with CV disease; however, cardiologists face several challenges in managing body weight in this population. Many may not consider obesity as a therapeutic target probably because there were no previous highly effective and safe pharmacologic interventions to consider. In addition, they may not have the expertise or resources to implement lifestyle interventions and may have limited familiarity with obesity pharmacotherapy. Moreover, the long-term CV effects of obesity pharmacotherapy remain uncertain due to limited CV outcome data with weight loss as the primary intervention. Although current CV guidelines recognize the importance of weight loss, they primarily focus on lifestyle modifications, with fewer details on strategies to utilize obesity pharmacotherapy and surgery. However, the recent 2022 American Diabetes Association/European Association for the Study of Diabetes consensus on the management of Type 2 diabetes has moved up weight management to the front of the treatment algorithm, by prioritizing the use of pharmacologic interventions such as glucagon-like peptide-1 receptor agonists and dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists, which have potent weight-lowering effects, in addition to glucose-lowering effects.
Hypothesis: The investigators hypothesise that weight loss treatment with semaglutide is superior to weight loss with state-of-the-art calorie-restricted diet in improving the peak oxygen uptake (ml/min/kg) after 52 weeks as a marker of physical performance (and with prognostic implications) in patients with obesity and heart failure with reduced ejection fraction.
Design: This is a investigator-initiated, parallel-group, 2-arm assessor-blinded, open-label, randomised, controlled trial (RCT) comparing the effect of weight loss using low-calorie replacement diet to weight loss using semaglutide in obese patients with heart failure with reduced ejection fraction. Subjects will be randomised in a 1:1 ratio to receive either low-calorie replacement diet or semaglutide.The subjects wil be followed for 52 weeks during the intervention period. The patients will be examined at 16 weeks (where the weight loss is anticipated to be approximately equal in the two groups) and after 52 weeks.
Primary, secondary and exploratory objectives are listed below. The exploratory objectives are mostly embedded mechanistic studies of an exploratory nature and therefore hypothesis-generating in the RCT.
Intervention: Subjects will be treated with semaglutide once weekly or a weight loss intervention consisting of a calorie-restricted diet and dietary advice on top of standard of care, which covers management of heart failure medication, CV risk factors and healthy lifestyle counselling.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- This is a investigator-initiated, parallel-group, 2-arm assessor-blinded, open-label, randomised, clinical trial
| Arm | Type | Receives |
|---|---|---|
| Semaglutide intervention group | Experimental | Drug: Semaglutide Injectable ProductDose-escalation of semaglutide will take place during the first 16 weeks after randomisation (week 0). Patients will start at the 0.25 mg once-weekly dose and follow dose-escalation schedule (0.25, 0.5, 1.0, 1.7 and 2.4 mg). For all subjects we aim at reaching the recommended target dose of 2.4 mg semaglutide once weekly for the rest of the period of total 52 weeks. |
| Calorie-restricted diet intervention group | Active comparator | Dietary Supplement: Calorie-restricted dietIn short, the weight loss program in the calorie-restricted diet group consists of 3 phases after randomisation (week 0). An initial weight loss phase of 8 weeks with 800 calories/day, a food re-introduction phase for 8 weeks and a weight loss maintenance phase for the rest of the period of total 52 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female, age ≥ 18 years at the time of signing informed consent
- Body mass index (BMI) ≥ 30 kg/m2
- Heart failure with New York Heart Association (NYHA)-class 1-3 and reduced ejection fraction (EF≤40%) established by either:
- On stable optimal medical heart failure therapy for at least 4 weeks
Key exclusion criteria (15 listed)
- Cardiovascular-related:
- Glycaemia-related:
- General safety:
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 |
|---|---|---|
| Semaglutide Injectable ProductWeight loss using Semaglutide | Drug | Semaglutide intervention group |
| Calorie-restricted dietWeight loss by calorie-restricted diet program followed by a weight loss maintenance follow-up program | Dietary supplement | Calorie-restricted diet intervention group |
Primary outcome
Peak oxygen uptake
Time frame: The patients will be examined after 0, 16 and 52 weeks
To examine the effect of weight loss on mean change in peak oxygen uptake at 52 weeks between semaglutide and calorie-restricted group compared to baseline (Measured in ml O2/(kg x min))
4 secondary outcomes
The Clinical Summary Score of the Kansas City Cardiomyopathy Questionnaire (KCCQ-CSS)
Time frame: The patients will be examined after 0, 16 and 52 weeks.
6-min walk distance (6MWD)
Time frame: The patients will be examined after 0, 16 and 52 weeks
End-systolic volume of the left ventricle assessed by Cardiac MRI
Time frame: The patients will be examined after 0, 16 and 52 weeks
N-terminal pro-B-type natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) change
Time frame: The patients will be examined after 0, 16 and 52 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2026.
- Individual participant dataSharing planned: No
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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.
Jens D Hove principal investigator
Amager-Hvidovre Universitetshospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Semaglutide Injectable Product and Calorie-restricted diet in people with Heart Failure With Reduced Ejection Fraction and Obesity, run by Jens D Hove, MD,PHD at 1 site in Denmark.
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 15 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: looking for participants now, as of the sponsor's last update on 23 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jens D Hove, MD, PhD (+4538623218, jens.dahlgaard.hove@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak oxygen uptake (time frame: The patients will be examined after 0, 16 and 52 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Jun 2026; AzTrials last refreshed its copy on 26 Oct 2026.