GLP-1 receptor agonist / dual GIP-GLP-1 receptor agonist (semaglutide, tirzepatide) for HF with obesity
AMT in HFpEF · Class IIaRemoval by dialysis
What each drug's prescribing information says about removal by (haemo)dialysis. Where the label is silent, this page says so rather than inferring from protein binding.
- SemaglutideLabel does not address dialysis removal
The semaglutide labels contain no statement on dialysis removal.
- TirzepatideLabel does not address dialysis removal
The tirzepatide labels contain no statement on dialysis removal.
Drugs and doses
| Drug | Brands | Start | Target | Kidney dosing |
|---|---|---|---|---|
| Semaglutide (subcutaneous) | Wegovy, Ozempic | 0.25 mg s.c. once weekly (escalate every 4 weeks) | 2.4 mg s.c. once weekly (Wegovy; STEP-HFpEF dose) | No dose adjustment for renal impairment (Ozempic label, including kidney failure). The 2026 Wegovy label has no renal-impairment subsection; its PK statement covers eGFR 30-<90 only. Monitor kidney function if GI losses cause volume depletion (AKI warning). |
| Tirzepatide (subcutaneous) | Zepbound, Mounjaro | 2.5 mg s.c. once weekly for 4 weeks (escalate by 2.5 mg every >=4 weeks) | 15 mg s.c. once weekly (SUMMIT target; label maintenance 5, 10 or 15 mg) | No dose adjustment for any degree of renal impairment including ESRD (Zepbound and Mounjaro labels); monitor kidney function if GI adverse reactions cause volume depletion. |
Status by kidney stage
| Stage | Initiate | Continue |
|---|---|---|
| G1 | Recommended ESC 2026 IIa for symptomatic HF with LVEF >=45% and BMI >=30 regardless of diabetes; no kidney restriction at normal eGFR. | Recommended Continue long term; no renal dose adjustment. |
| G2 | Recommended Same as G1; ESC CVD-CKD 2026 IIa covers HFpEF + CKD with eGFR >=15. | Recommended Continue; no renal dose adjustment. |
| G3a | Recommended ESC CVD-CKD 2026 IIa (eGFR >=15); over half of SUMMIT participants had CKD stage 3 or worse. | Recommended Continue; an early eGFR dip may occur but long-term kidney function is protected. |
| G3b | Recommended ESC CVD-CKD 2026 IIa (eGFR >=15); GI adverse events are not eGFR-dependent and no renal safety signal. | Recommended Continue; no renal dose adjustment. |
| G4 | Allowed ESC CVD-CKD 2026 IIa nominally covers eGFR >=15, and labels need no dose change, but HF-trial evidence at eGFR 15-29 is sparse (FLOW floor 25). | Recommended Continue if tolerated; long-term kidney-protective effect, no renal dose adjustment. |
| G5 | Use with caution Labels need no dose change even in ESRD, but ESC CVD-CKD 2026 limits its HF recommendation to eGFR >=15 and data are lacking; individualize. | Use with caution May be continued with attention to GI losses and volume status; no HF outcome data below eGFR 15. |
| dialysis | Use with caution No label restriction (no dose change incl. kidney failure/ESRD) but no HF-obesity trial data in dialysis; outside the ESC eGFR >=15 recommendation. | Use with caution Post hoc pooled data suggest continuing semaglutide after dialysis initiation appears safe; efficacy unproven. |
| aki | Use with caution Labels warn of AKI from GI-related volume depletion (some requiring hemodialysis); defer initiation/escalation until volume status and kidney function recover. | Use with caution Temporarily withhold if unable to maintain oral intake (sick-day rules); restart after recovery. |
| transplant | Allowed ESC CVD-CKD 2026: GLP-1 RAs may be considered in kidney transplant recipients with T2D; intentional weight loss before/after transplant encouraged. No HF-specific data. | Allowed Continue; no transplant-specific restriction in labels. |
Cutoffs recorded from the sources
- other >= 30 kg/m2 → recommended (initiate; semaglutide, tirzepatide)“Semaglutide or tirzepatide should be considered for patients with symptomatic HF, LVEF ≥45%, and BMI ≥30 kg/m2, regardless of diabetes status, to reduce body weight, and improve exercise capacity and QoL.” — esc2026, p. 12
- other >= 45 % → recommended (initiate; semaglutide, tirzepatide)“Semaglutide or tirzepatide should be considered for patients with symptomatic HF, LVEF ≥45%, and BMI ≥30 kg/m2, regardless of diabetes status, to reduce body weight, and improve exercise capacity and QoL.” — esc2026, p. 12
- other >= 50 % → allowed (initiate; tirzepatide)“Participants with HFpEF aged ≥40 years with chronic class II–IV HF, left ventricular ejection fraction ≥50% and a BMI ≥30 kg m−2 were enrolled.” — borlaug2025-summit, Methods: Trial design
- egfr < 15 mL/min/1.73m2 → caution (initiate; semaglutide, tirzepatide)“Treatment with a GLP-1RA (semaglutide) or glucose-dependent insulinotropic polypeptide and GLP-1RA (tirzepatide) should be considered in patients with HFpEF and CKD with an eGFR ≥15 mL/min/1.73 m2 and LVEF ≥45% with or without diabetes who are obese, to reduce weight and improve quality of life.” — esc2026-ckd, p. 40
- other < 30 % fall in eGFR after initiation → allowed (continue; semaglutide, tirzepatide)“The therapies discussed in Section 5.5 are known to cause an acute dip in eGFR upon initiation, with clinicians typically tolerating <30% dips,9 since dips might reflect the drugs correcting maladaptive hyperfiltration in CKD.” — esc2026-ckd, p. 31
- egfr >= 25 mL/min/1.73m2 → recommended (initiate; semaglutide)“A GLP-1RA (subcutaneous semaglutide 1.0 mg/week after dose titration) is recommended in patients with CKD who have type 2 diabetes with eGFR 25–49 mL/min/1.73 m2 and uACR ≥10 mg/mmol (≥100 mg/g) or eGFR 50–74 mL/min/1.73 m2 and uACR ≥30 mg/mmol (≥300 mg/g) to reduce the risk of CKD progression and cardiovascular events, irrespective of glycaemic control.” — esc2026-ckd, p. 31
Trial evidence (informational)
- STEP-HFpEF · HF, LVEF >=45%, BMI >=30, no diabetes (n=529)KCCQ-CSS, body weight, 6MWD at 52 weeks: Greater weight loss and larger symptom/physical-limitation and 6MWD improvement vs placebo (ACC: 13.3% weight reduction)“The STEP-HFpEF trial enrolled 529 patients with LVEF ≥45%, HF symptoms, a BMI ≥30 kg/m2, and with no history of diabetes.” — esc2026-supp, p. 32
- STEP-HFpEF DM · HFpEF, obesity and T2DKCCQ-CSS, body weight: Similar results to STEP-HFpEF“Similar results were found with semaglutide in patients with HFpEF, obesity, and diabetes in the STEP-HFpEF DM trial.” — esc2026-supp, p. 32
- Pooled SELECT, FLOW, STEP-HFpEF, STEP-HFpEF DM · 3743 participants with HFpEFCV death or worsening HF: Reduced; no effect on CV death alone (post hoc)“In a post-hoc pooled, participant-level analysis of SELECT, STEP-HFpEF, STEP-HFpEF DM, and FLOW trials, semaglutide reduced the risk of the composite endpoint of CV death or worsening HF events, without an effect on CV mortality alone, in 3743 participants with HFpEF.” — esc2026-supp, p. 32
- SUMMIT · HFpEF (LVEF >=50%), BMI >=30, n=731CV death or worsening HF event: HR 0.62 (95% CI 0.41-0.95)“with a 38% lower risk of the composite of cardiovascular death or worsening HF events (HR 0.62, 95% CI 0.41–0.95) over 52 weeks.” — esc2026-ckd, p. 37
- SUMMIT (kidney secondary analysis) · SUMMIT, mean eGFR 55eGFR change: eGFR +2.9 mL/min/1.73m2 vs placebo at 52 weeks after a non-significant early dip“As compared with placebo, treatment with tirzepatide was associated with a numerical decrease in eGFR at 12 weeks that was not statistically significant (ETD −1.1 ml min−1 1.73 m−2, 95% CI −2.7 to 0.4; P = 0.148), followed by a significant improvement in eGFR at 52 weeks with tirzepatide compared with placebo (ETD 2.9 ml min−1 1.73 m−2, 95% CI 0.9 to 4.9; P = 0.004) (Table 3 and Fig. 3a).” — borlaug2025-summit, Results: Effects of tirzepatide on cardiac injury and kidney function
- FLOW · T2D + CKD, eGFR 25-75, UACR >100-<5000 mg/gKidney failure, >=50% eGFR decline, kidney or CV death: HR 0.76 (95% CI 0.66-0.88)“Allocation to weekly subcutaneous semaglutide 1 mg reduced the risk of the primary composite kidney outcome of kidney failure (dialysis, transplantation, or eGFR <15 mL/min/1.73 m2), ≥50% eGFR decline from baseline, or death from kidney-related or cardiovascular causes by 24% compared with placebo (HR 0.76, 95% CI 0.66–0.88).” — esc2026-ckd, p. 30
Acute kidney injury
Both labels warn of AKI (sometimes requiring hemodialysis) from GI-loss dehydration; monitor kidney function during initiation/escalation and hold on sick days. ESC 2026 notes an acute eGFR fall with long-term kidney protection, so a small early dip is not a reason to stop.
“Monitor renal function in patients reporting adverse reactions to WEGOVY that could lead to volume depletion, especially during dosage initiation and escalation of WEGOVY.”
WEGOVY (semaglutide) injection / tablets, prescribing information, Novo Nordisk (2026)· Warnings and Precautions 5.5 Source“Notably, in patients with HFpEF, semaglutide and tirzepatide may acutely reduce eGFR; however, they exhibit a long-term protective effect on kidney function.”
“Renal: acute renal failure or worsening of chronic renal failure, sometimes requiring hemodialysis”
Dialysis
Labels (Ozempic, Zepbound/Mounjaro) report no PK change in kidney failure/ESRD and require no dose change; no HF trial included dialysis patients; ESC CVD-CKD HF recommendation stops at eGFR >=15. Post hoc data support safety of continuing semaglutide after dialysis start.
Trials: Klein 2026 pooled post hoc (SUSTAIN-6, SELECT, FLOW, SOUL)
“Among 34,064 participants randomized across the trials, 307 initiated dialysis, of whom 165 participants randomized to semaglutide (n = 71) or placebo (n = 94) remained on treatment.”
Klein KR et al. Safety of Semaglutide After Dialysis Initiation: An Individual-Level Pooled Analysis. Diabetes Care 2026 (2026)· Abstract, Results Source“The MACE event rates were 9.7 and 16.1 events per 100 person-years, and all-cause mortality event rates were 13.8 and 18.1 events per 100 person-years, in the semaglutide and placebo groups, respectively.”
Klein KR et al. Safety of Semaglutide After Dialysis Initiation: An Individual-Level Pooled Analysis. Diabetes Care 2026 (2026)· Abstract, Results Source
Kidney transplant
ESC CVD-CKD 2026: GLP-1 RAs may be considered in kidney transplant recipients with T2D; weight loss before and after transplantation encouraged. No HF-specific transplant data.
“Extrapolating data from non-kidney transplant recipients with diabetes, both SGLT2 inhibitors and GLP-1RAs may be considered in kidney transplant recipients with type 2 diabetes to treat hyperglycaemia and modify cardiovascular risk, but RCTs should ideally be conducted to assess effects on cardiovascular outcomes and graft outcomes, and to assess safety.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 72 Source
Albuminuria
The HF recommendation does not depend on albuminuria. The separate kidney-protection indication of semaglutide (T2D + CKD) is albuminuria-dependent, and ESC CVD-CKD 2026 is internally inconsistent on the exact eGFR/uACR window (text 25-89 with uACR >=100 mg/g; table 25-49 with >=100 or 50-74 with >=300).
“treatment with a GLP-1RA (semaglutide 1.0 mg subcutaneous injection weekly, which was well tolerated in FLOW) is recommended to reduce risk of CKD progression and cardiovascular events in patients with type 2 diabetes (irrespective of glycaemic control) and CKD with eGFR 25–89 mL/min/1.73 m2 and uACR ≥10 mg/mmol (≥100 mg/g).”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 30 Source“A GLP-1RA (subcutaneous semaglutide 1.0 mg/week after dose titration) is recommended in patients with CKD who have type 2 diabetes with eGFR 25–49 mL/min/1.73 m2 and uACR ≥10 mg/mmol (≥100 mg/g) or eGFR 50–74 mL/min/1.73 m2 and uACR ≥30 mg/mmol (≥300 mg/g) to reduce the risk of CKD progression and cardiovascular events, irrespective of glycaemic control.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 31 Source“FLOW (NCT03819153) was a randomized, double-blind, placebo-controlled, event driven trial in adults with type 2 diabetes mellitus and chronic kidney disease (eGFR 25 to 75 mL/min/1.73m2 with urine albumin-to- creatinine ratio [UACR] >100 mg/g and <5000 mg/g).”
Monitoring
No routine extra creatinine checks are needed after GLP-1 RA initiation beyond standard CKD monitoring unless volume depletion is a concern; check kidney function if vomiting/diarrhoea occur; monitor glucose in diabetes (hypoglycaemia risk with insulin/SU). Discontinue if pancreatitis suspected.
“Although monitoring of potassium and creatinine is routine when initiating ACEI/ARBs and MRAs, on initiation of an SGLT2 inhibitor or GLP-1RA, we do not consider it necessary to routinely monitor creatinine/eGFR more frequently than for standard CKD monitoring, unless there is another reason (such as concern about volume depletion).”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 31 Source“If pancreatitis is suspected, discontinue WEGOVY and initiate appropriate management.”
WEGOVY (semaglutide) injection / tablets, prescribing information, Novo Nordisk (2026)· Warnings and Precautions 5.2 Source“If pancreatitis is suspected, discontinue ZEPBOUND and initiate appropriate management.”
“Practice Point 4.2.4: The risk of hypoglycemia is generally low with GLP-1 RA when used alone, but risk is increased when GLP-1 RA is used concomitantly with other medications such as sulfonylureas or insulin.”
In-hospital initiation
No source addresses starting GLP-1 RA during HF hospitalization; ESC/ACC position them as chronic outpatient therapy. Peri-procedural holding (aspiration risk) per ACC 2026 HFpEF slide notes.
“Patients should be instructed to inform their anesthesiologist or proceduralist about their GLP1 medication, which may need to be held before procedures, usually 1 week.”
2026 ACC HFpEF ECDP slides (2026)· slide 21
Outpatient
ACC 2026 HFpEF pathway: add incretin therapy when BMI >=30 kg/m2 on top of SGLT2i + MRA; accompany with exercise and nutrition to limit sarcopenia.
“For HFpEF and BMI ≥30, consider semaglutide or tirzepatide. Accompany with exercise & nutrition to prevent sarcopenic obesity”
2026 ACC HFpEF ECDP slides (2026)· slide 39“Add incretin-based therapy (semaglutide or tirzepatide) when BMI ≥30 kg/m² — to improve health status and exercise function and to potentially reduce worsening HF events”
2026 ACC HFpEF ECDP slides (2026)· slide 30
Where sources disagree
LVEF threshold for GLP-1 RA/tirzepatide in HF (>=45% vs HFpEF definition >=50%)
“Semaglutide or tirzepatide should be considered for patients with symptomatic HF, LVEF ≥45%, and BMI ≥30 kg/m2, regardless of diabetes status, to reduce body weight, and improve exercise capacity and QoL.”
“(i) HFrEF: characterized by LVEF <50% and symptoms and/or signs of HF.”
“Participants were eligible if they had symptomatic HF, LVEF ≥ 45%, BMI ≥ 30 kg/m2, New York Heart Association (NYHA) functional class II–IV, KCCQ-CSS < 90 points”
Shah SJ et al. Semaglutide and diuretic use in obesity-related HFpEF: a pooled analysis of the STEP-HFpEF and STEP-HFpEF-DM trials. Eur Heart J 2024 (2024)· Methods: Study design and participants Source“Participants with HFpEF aged ≥40 years with chronic class II–IV HF, left ventricular ejection fraction ≥50% and a BMI ≥30 kg m−2 were enrolled.”
Borlaug BA et al. Effects of tirzepatide on circulatory overload and end-organ damage in heart failure with preserved ejection fraction and obesity: a secondary analysis of the SUMMIT trial. Nat Med 2025 (2025)· Methods: Trial design Source
Tool uses esc2026: Use the ESC 2026 LVEF >=45% criterion (it mirrors STEP-HFpEF); the project's HFpEF branch starts at LVEF >=50%, so patients with LVEF 45-49% (HFrEF in ESC 2026 and in the project) also qualify. Flag that tirzepatide outcome data (SUMMIT) are only for LVEF >=50%. Owner to decide whether to show the drug in the HFrEF branch for LVEF 45-49%.
eGFR floor / dialysis
“No dosage adjustment of ZEPBOUND is recommended for patients with renal impairment. In subjects with renal impairment including end-stage renal disease (ESRD), no change in tirzepatide pharmacokinetics (PK) was observed [see Clinical Pharmacology (12.3)].”
“In patients with HF and CKD with LVEF ≥45% and obesity, treatment with a GLP-1RA (semaglutide) or combined glucose-dependent insulinotropic polypeptide and GLP-1RA (tirzepatide) should be considered in patients with eGFR >15 mL/min/1.73 m2 with or without diabetes, for weight loss and improved quality of life.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 37 Source“Treatment with a GLP-1RA (semaglutide) or glucose-dependent insulinotropic polypeptide and GLP-1RA (tirzepatide) should be considered in patients with HFpEF and CKD with an eGFR ≥15 mL/min/1.73 m2 and LVEF ≥45% with or without diabetes who are obese, to reduce weight and improve quality of life.”
2026 ESC Guidelines for the management of cardiovascular disease and chronic kidney disease, in collaboration with the ERA (2026)· p. 40 Source“However, their use is currently not recommended in patients with an eGFR <15 ml/min/1.73 m2 due to the lack of sufficient data.”
Touzot M et al. Prescription of off-label medications in patients on dialysis. Clin Kidney J 2026 (PMC13184690) (2026)· Future drugs/perspectives: GLP-1 receptor agonists Source
Tool uses fda-tirzepatide-zepbound: Label > guideline: no renal contraindication or dose change, so G5/dialysis are not 'not-recommended'; but because the ESC recommendation stops at eGFR 15 and evidence is lacking, display 'caution'. Note the ESC CVD-CKD text (>15) vs table (>=15) inconsistency; the engine should treat exactly 15 as covered (table wording).
No FDA heart-failure indication vs ESC IIa
“Effect on heart failure has not been established.”
WEGOVY (semaglutide) injection / tablets, prescribing information, Novo Nordisk (2026)· Section 14.1 (SELECT) Table footnote 6 Source“to reduce excess body weight and maintain weight reduction long term in adults with obesity or adults with overweight in the presence of at least one weight-related comorbid condition.”
“Semaglutide or tirzepatide should be considered for patients with symptomatic HF, LVEF ≥45%, and BMI ≥30 kg/m2, regardless of diabetes status, to reduce body weight, and improve exercise capacity and QoL.”
Tool uses esc2026: The label does not prohibit use; obesity (BMI >=30) is itself a labelled indication, so HF-obesity patients are on-label for weight reduction. Display the ESC IIa with a note that HF benefit is not a labelled claim in the US.
Diabetes without obesity: ESC 2026 text vs recommendation table
“Semaglutide or tirzepatide should be added if not contraindicated in patients with HFpEF and T2DM, especially if they are also obese.”
“Semaglutide or tirzepatide should be considered for patients with symptomatic HF, LVEF ≥45%, and BMI ≥30 kg/m2, regardless of diabetes status, to reduce body weight, and improve exercise capacity and QoL.”
Tool uses esc2026: Only the recommendation-table wording (BMI >=30) is graded; treat HFpEF + T2D without obesity as a text-level suggestion (show as informational, not as the IIa).
Open questions
- Should the tool offer semaglutide/tirzepatide in the HFrEF branch for LVEF 45-49% (literally covered by ESC 2026 IIa, LVEF >=45%) or only in the HFpEF (LVEF >=50%) branch? Tirzepatide data (SUMMIT) are LVEF >=50% only.
- G4 initiation set to 'allowed' (conservative) although ESC CVD-CKD 2026 IIa nominally covers eGFR >=15; confirm.
- G5/dialysis set to 'caution' for both initiate and continue despite labels requiring no dose change; Klein 2026 supports continuing semaglutide after dialysis start. Confirm whether 'continue' in dialysis should be 'allowed'.
- HFpEF + T2D without obesity: ESC text says GLP-1 RA 'should be added'; not a graded recommendation. Show or not?
- BMI threshold for Asian patients (lower cut-offs) is not addressed by ESC 2026 HF; keep BMI >=30 for all?
- Lilly's HFpEF supplemental application for tirzepatide is not reflected on the 2026-09 Zepbound label (no HF indication); re-check labels periodically.