Evidence reference only. Not medical advice, not a dosing guide, and not a recommendation to use any drug.
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heart-failure

12 findings across 3 drug records. Domain pages are descriptive indexes, not advice.

Most represented records

Liraglutide (5)

Semaglutide (5)

Tirzepatide (2)

Evidence spread

High evidence 4 Moderate evidence 7 Low evidence 1 Very low evidence 0

Liraglutide MARKETED
heart-failure No change
Moderate evidence

FIGHT: in patients recently hospitalised for acute HFrEF, liraglutide did NOT improve post-hospitalisation clinical stability (null), with numerically more deaths and...

Margulies KB et al. (FIGHT), JAMA, 2016;316:500-508 Source
Full findingFIGHT: in patients recently hospitalised for acute HFrEF, liraglutide did NOT improve post-hospitalisation clinical stability (null), with numerically more deaths and rehospitalisations.
PopulationN=300, established HFrEF (median LVEF 25%), recently hospitalised, 59% T2D; 180 days; phase 2 RCT vs placebo.
Fundingacademic-NHLBI (study drug supplied by Novo Nordisk)
Scope limitsCAUTION pole: null primary; numerically worse death/rehospitalisation on liraglutide (non-significant). PMID/DOI verified.
Comparatorsplacebo
Liraglutide MARKETED
heart-failure Mixed
High evidence

LIVE: in stable chronic HFrEF on optimal therapy, liraglutide did NOT change LV systolic function but raised heart rate and was associated with more serious cardiac...

Jorsal A et al. (LIVE), Eur J Heart Fail, 2017;19:69-77 Source
Full findingLIVE: in stable chronic HFrEF on optimal therapy, liraglutide did NOT change LV systolic function but raised heart rate and was associated with more serious cardiac adverse events (safety caution).
PopulationN=241, LVEF <=45% (mean ~34%), clinically stable, with/without diabetes; 24 weeks; investigator-initiated RCT vs placebo.
Fundinginvestigator-initiated (academic; not manufacturer-run)
Scope limitssmall sample (N~241)
Comparatorsplacebo
Liraglutide MARKETED
heart-failure Decrease
Moderate evidence

In a LIVE substudy (231 HFrEF patients), liraglutide reduced natriuretic peptides only in the type-2-diabetes subgroup (NT-proBNP -25%, MR-proANP -27% vs placebo) with...

Nielsen R et al., Diabetes Obes Metab 2020;22(11):2141-2150 (LIVE natriuretic-peptide sub... Source
Full findingIn a LIVE substudy (231 HFrEF patients), liraglutide reduced natriuretic peptides only in the type-2-diabetes subgroup (NT-proBNP -25%, MR-proANP -27% vs placebo) with no change in non-diabetic patients (significant T2D interaction), indicating any neurohormonal benefit in HFrEF was confined to the diabetic subset.
PopulationLIVE substudy, 231 chronic HFrEF patients (LVEF <=45%), with and without T2D, 24 wk; NCT01472640
Fundinginvestigator-initiated (academic; not manufacturer-run)
Scope limitssurrogate/exploratory endpoint; small sample (N~231)
Comparatorsplacebo
Liraglutide MARKETED
heart-failure No change
Moderate evidence

In a LIVE PET sub-study (36 non-diabetic HFrEF patients), liraglutide did NOT change myocardial glucose uptake, myocardial blood flow or myocardial flow reserve versus...

Nielsen R et al., J Nucl Cardiol 2019;26(2):585-597 (LIVE PET substudy) Source
Full findingIn a LIVE PET sub-study (36 non-diabetic HFrEF patients), liraglutide did NOT change myocardial glucose uptake, myocardial blood flow or myocardial flow reserve versus placebo despite lowering weight and HbA1c - so the increased cardiac-event signal with liraglutide in chronic HF does not appear to be mediated by changes in myocardial perfusion or substrate uptake.
PopulationLIVE PET substudy, 36 non-diabetic HFrEF patients (LVEF <=45%); NCT01472640
Fundinginvestigator-initiated (academic; not manufacturer-run)
Scope limitssurrogate/exploratory endpoint; small sample (N~36)
Comparatorsplacebo
Liraglutide MARKETED
heart-failure No change
Low evidence

A systematic review of the two isolating GLP-1RA HFrEF RCTs (FIGHT and LIVE, combined n=541, 24-week liraglutide) found no benefit and an adverse-leaning signal - no...

Hamad F et al., Curr Diabetes Rev 2021;17(3):280-292 (systematic review FIGHT+LIVE) Source
Full findingA systematic review of the two isolating GLP-1RA HFrEF RCTs (FIGHT and LIVE, combined n=541, 24-week liraglutide) found no benefit and an adverse-leaning signal - no between-group difference in FIGHT's global rank/deaths/HF rehospitalisation and no LVEF change in LIVE - concluding liraglutide use in HFrEF was associated with increased risk of HF-related outcomes.
Populationsystematic review of FIGHT + LIVE (two GLP-1RA HFrEF RCTs), combined n=541
Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)
Scope limitsconference/abstract-level
Comparatorsplacebo
Semaglutide MARKETED
heart-failure Increase
High evidence

STEP-HFpEF: in HFpEF with obesity but without diabetes, semaglutide improved HF symptoms/physical limitations (KCCQ-CSS) versus placebo at 52 weeks.

Kosiborod MN et al. (STEP-HFpEF), NEJM, 2023;389:1069-1084 Source
PopulationN=529, HFpEF (EF >=45%), BMI >=30, no T2D; 52 weeks; RCT vs placebo.
Fundingindustry - Novo Nordisk
Scope limitsidentifier not fully verified; magnitude web/secondary-sourced
Comparatorsplacebo
Semaglutide MARKETED
heart-failure Increase
High evidence

STEP-HFpEF DM: in HFpEF with obesity AND T2D, semaglutide improved KCCQ-CSS, weight, 6MWD and inflammation versus placebo at 52 weeks.

Kosiborod MN et al. (STEP-HFpEF DM), NEJM, 2024;390:1394-1407 Source
PopulationN=616, HFpEF with BMI >=30 and T2D; 52 weeks; RCT vs placebo.
Fundingindustry - Novo Nordisk
Scope limitsKCCQ-CSS gain numerically smaller than non-diabetic STEP-HFpEF. PMID/DOI verified.
Comparatorsplacebo
Semaglutide MARKETED
heart-failure Decrease
Moderate evidence

Pooled post-hoc (SELECT, FLOW, STEP-HFpEF, STEP-HFpEF DM): in participants with HFpEF history, semaglutide reduced the composite of CV death or worsening HF events,...

Kosiborod MN et al., Lancet, 2024;404:949-961 Source
Full findingPooled post-hoc (SELECT, FLOW, STEP-HFpEF, STEP-HFpEF DM): in participants with HFpEF history, semaglutide reduced the composite of CV death or worsening HF events, and worsening HF events alone; no significant effect on CV death alone.
PopulationN=3,743 with HFpEF history pooled from four RCTs; 1914 sema vs 1829 placebo; ITT.
Fundingindustry-Novo Nordisk
Scope limitspost-hoc (not prespecified)
Comparatorsplacebo
Semaglutide MARKETED
heart-failure Decrease
Moderate evidence

In a secondary analysis of the STEP-HFpEF programme, inflammation (CRP >=2 mg/L) was present in 71% of obesity-related HFpEF patients; semaglutide reduced CRP more...

Verma S et al., J Am Coll Cardiol 2024;84(17):1646-1662 (STEP-HFpEF inflammation analysis) Source
Full findingIn a secondary analysis of the STEP-HFpEF programme, inflammation (CRP >=2 mg/L) was present in 71% of obesity-related HFpEF patients; semaglutide reduced CRP more than placebo across all baseline CRP strata, and the CRP fall was largely INDEPENDENT of the magnitude of weight loss.
Populationsecondary analysis of pooled STEP-HFpEF programme, HFpEF + obesity
Fundingindustry - Novo Nordisk (trial sponsor; sponsor-authored)
Scope limitssurrogate/exploratory endpoint; sponsor-authored COI (Novo Nordisk)
Comparatorsplacebo
Semaglutide MARKETED
heart-failure Decrease
Moderate evidence

In a prespecified echocardiography substudy of the pooled STEP-HFpEF programme (491 of 1145 participants), semaglutide 2.4 mg attenuated left-atrial remodelling (LA...

Solomon SD et al., J Am Coll Cardiol 2024;84(17):1587-1602 (STEP-HFpEF echo substudy) Source
Full findingIn a prespecified echocardiography substudy of the pooled STEP-HFpEF programme (491 of 1145 participants), semaglutide 2.4 mg attenuated left-atrial remodelling (LA volume difference -6.13 mL, p=0.0013) and right-ventricular enlargement and improved diastolic indices, with no change in LV mass or systolic function; greater weight loss correlated with greater LA-volume reduction.
Populationprespecified echo substudy of pooled STEP-HFpEF + STEP-HFpEF DM, 491 of 1145 participants, HFpEF + obesity, 52 wk
Fundingindustry - Novo Nordisk (trial sponsor; sponsor-authored)
Scope limitssurrogate/exploratory endpoint; sponsor-authored COI (Novo Nordisk)
Comparatorsplacebo
Tirzepatide MARKETED
heart-failure Decrease
High evidence

SUMMIT: in HFpEF with obesity, tirzepatide reduced the composite of CV death or worsening HF event and improved KCCQ-CSS versus placebo.

Packer M et al. (SUMMIT), NEJM, 2025;392:427-437 Source
PopulationN=731, HFpEF (EF >=50%), BMI >=30; median follow-up 104 weeks; RCT vs placebo.
Fundingindustry - Eli Lilly and Company
Scope limitsfew events/wide CI
Comparatorsplacebo
Tirzepatide MARKETED
heart-failure Mixed
Moderate evidence

In a mechanistic secondary analysis of SUMMIT, tirzepatide at 52 weeks reduced systolic blood pressure (-5 mmHg), estimated blood volume (-0.58 L), CRP (-37.2%),...

Borlaug BA et al., Nat Med 2025;31(2):544-551 (SUMMIT mechanistic secondary) Source
Full findingIn a mechanistic secondary analysis of SUMMIT, tirzepatide at 52 weeks reduced systolic blood pressure (-5 mmHg), estimated blood volume (-0.58 L), CRP (-37.2%), NT-proBNP and troponin T, and INCREASED eGFR (+2.90 mL/min/1.73m2/yr) while lowering urine albumin-creatinine ratio - interpreted as reduced volume/pressure overload and mitigated cardiovascular-kidney end-organ injury.
Populationmechanistic secondary analysis of SUMMIT (HFpEF + obesity); NCT04847557
Fundingindustry - Eli Lilly (trial sponsor; sponsor-authored)
Scope limitssurrogate/exploratory endpoint; sponsor-authored COI (Eli Lilly)
Comparatorsplacebo