12 findings across 3 drug records. Domain pages are descriptive indexes, not advice.
The grade rates how strong the evidence is, not how good or safe the drug is. A low or very-low grade means the evidence is thin, not that an effect is harmful or ruled out.
Most represented records
Liraglutide (5)
Semaglutide (5)
Tirzepatide (2)
Evidence spread
High evidence 4Moderate evidence 7Low evidence 1Very low evidence 0
LiraglutideMARKETED
Heart failureNo 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...
SourceMargulies KB et al. (FIGHT), JAMA, 2016;316:500-508Source
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)
Comparatorsplacebo
LiraglutideMARKETED
Heart failureMixed
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...
SourceJorsal A et al. (LIVE), Eur J Heart Fail, 2017;19:69-77Source
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).
Fundinginvestigator-initiated (academic; not manufacturer-run)
Comparatorsplacebo
LiraglutideMARKETED
Heart failureDecrease
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...
SourceNielsen 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)
Comparatorsplacebo
LiraglutideMARKETED
Heart failureNo 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...
SourceNielsen 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)
Comparatorsplacebo
LiraglutideMARKETED
Heart failureNo 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...
SourceHamad 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)
Comparatorsplacebo
SemaglutideMARKETED
Heart failureIncrease
High evidence
STEP-HFpEF: in HFpEF with obesity but without diabetes, semaglutide improved HF symptoms/physical limitations (KCCQ-CSS) versus placebo at 52 weeks.
SourceKosiborod MN et al. (STEP-HFpEF), NEJM, 2023;389:1069-1084Source
PopulationN=529, HFpEF (EF >=45%), BMI >=30, no T2D; 52 weeks; RCT vs placebo.
Fundingindustry - Novo Nordisk
Comparatorsplacebo
SemaglutideMARKETED
Heart failureIncrease
High evidence
STEP-HFpEF DM: in HFpEF with obesity AND T2D, semaglutide improved KCCQ-CSS, weight, 6MWD and inflammation versus placebo at 52 weeks.
SourceKosiborod MN et al. (STEP-HFpEF DM), NEJM, 2024;390:1394-1407Source
PopulationN=616, HFpEF with BMI >=30 and T2D; 52 weeks; RCT vs placebo.
Fundingindustry - Novo Nordisk
Comparatorsplacebo
SemaglutideMARKETED
Heart failureDecrease
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,...
SourceKosiborod MN et al., Lancet, 2024;404:949-961Source
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
Comparatorsplacebo
SemaglutideMARKETED
Heart failureDecrease
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...
SourceVerma 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)
Comparatorsplacebo
SemaglutideMARKETED
Heart failureDecrease
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...
SourceSolomon 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)
Comparatorsplacebo
TirzepatideMARKETED
Heart failureDecrease
High evidence
SUMMIT: in HFpEF with obesity, tirzepatide reduced the composite of CV death or worsening HF event and improved KCCQ-CSS versus placebo.
SourcePacker M et al. (SUMMIT), NEJM, 2025;392:427-437Source
PopulationN=731, HFpEF (EF >=50%), BMI >=30; median follow-up 104 weeks; RCT vs placebo.
Fundingindustry - Eli Lilly and Company
Comparatorsplacebo
TirzepatideMARKETED
Heart failureMixed
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%),...
SourceBorlaug 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)