The headline trial: STEP-HFpEF + FLOW (combined organ-protection evidence)
STEP-HFpEF (Kosiborod NEJM 2023) for HFpEF symptoms and weight; FLOW (Perkovic NEJM 2024) for kidney protection in T2D + CKD (sub-analyses extending to non-T2D CKD ongoing)
STEP-HFpEF 2023; FLOW 2024
Semaglutide 2.4 mg shows benefit in HFpEF symptoms + weight (STEP-HFpEF: KCCQ-CSS +7.8) AND kidney composite in T2D + CKD (FLOW: HR 0.76). The two trial populations overlap significantly (CKD is highly prevalent in HFpEF). The combined indication is currently filed under obesity-with-comorbidity, with HFpEF and CKD as supporting context.
Trial enrollment criteria
- HFpEF documented (LVEF at least 45 percent on echo)
- CKD stage 3 or 4 (eGFR 25 to 75)
- BMI greater than or equal to 30
- Stable diuretic regimen for at least 30 days
Does this trial apply to you?
HFpEF + CKD is highly prevalent (roughly half of all HFpEF patients have stage 3+ CKD). The combined PA case is filed under obesity-with-comorbidity with the cardiology and nephrology context layered in. Many payers (Aetna, Anthem, BCBS affiliates) updated their criteria in late 2024 to recognize the HFpEF + obesity stack as a stronger justification.
What to ask your prescriber
- Most recent echocardiogram (LVEF, diastolic function), eGFR, UACR, BNP/NT-proBNP
- NYHA class and KCCQ-CSS if available
- Whether the cardiology team and nephrology team have aligned on the prescribing pathway
- Diuretic adjustment plan during initial weight loss
Editorial notes
- Diuretic doses often need stepwise reduction in the first 12 weeks as preload and afterload drop with weight loss.
- Volume status monitoring is essential; HFpEF + CKD patients have narrow euvolemia windows.
- GLP-1 RA does not replace SGLT2 inhibitor or MRA therapy in HFpEF; these are complementary, not substitute.
Clinical trials for HFpEF with chronic kidney disease and obesity
Or browse the full GLP-1 clinical trials directory, filterable by condition, state and phase.
Take it to your prescriber: PA letter templates
Editable prior-authorization letter templates that cite the registration trial above. Pick the plan your prescriber will submit to, copy the template, fill in the patient-specific findings and have your clinician sign and submit.
Not seeing your plan? The full PA letter librarycovers 20 plans × 10 indications = 200 templates. The appeal letter library handles denials.
Drug profiles
Other GLP-1 conditions
Editorial provenance
Editorial review by John, Editor on 2026-05-23, against STEP-HFpEF + FLOW (combined organ-protection evidence) (STEP-HFpEF 2023; FLOW 2024). We do not yet have a credentialed medical reviewer on staff (actively recruiting). This page summarises public registration-trial data and FDA labeling. It is not clinician-authored medical advice.
Disclaimer
Educational summary of published registration trial data. Not medical advice. Not a substitute for evaluation by a treating clinician. Trial-level results do not guarantee individual outcomes. Discuss eligibility, contraindications, dose adjustments and drug interactions with your prescriber. We do not have a credentialed medical reviewer on staff yet (actively recruiting); the content below is editor-written from public registration-trial publications and FDA labeling, not clinician-authored medical advice.