A newly published study found that delivering furosemide through a subcutaneous route produces drug absorption and therapeutic effect comparable to what intravenous administration yields in people living with heart failure. At the HFSA Annual Scientific Meeting 2026, held in Phoenix, Arizona, two separate presentations brought these data into public view — one delivered by Alice Chan, DNP, and the other by Barbara Cornelius, MS, both affiliated with parent company MannKind.
Tochi Okwueze, a DNP-credentialed advanced heart failure provider and supervisor at the Ascension Medical Group heart failure clinic, spoke with a news outlet about what the research findings mean for how furosemide might be used going forward in heart failure care. Okwueze noted that earlier work with the original on-body infuser had already built a body of evidence around subcutaneous delivery in Class III patients, and that the shift to an autoinjector calls for confirming both the delivery route and the drug's absorption profile — a step she described as distinct from the question of bioequivalence between subcutaneous and intravenous furosemide, which prior research had addressed but had not, at that point, definitively closed.
Absorption into the bloodstream was the central concern of the first study, which examined subcutaneous furosemide delivered at two injection sites — the thigh and the upper arm. Enrolled participants were allocated across three treatment arms in equal proportions — intravenous furosemide, subcutaneous furosemide delivered into the thigh, and subcutaneous furosemide delivered into the upper arm — through a single-center, single-dose, open-label crossover design in which each assignment was made at random.
Patients receiving the intravenous formulation received two 40 mg boluses delivered two hours apart, whereas those on the subcutaneous route received a single 80 mg dose injected over a ten-second span. Plasma concentrations, urine output, and urinary sodium excretion were gathered by Chan and colleagues across an eight-hour window following dosing, while relative bioavailability underwent evaluation through geometric mean ratios derived from AUClast and AUCinf — with bioequivalence established only where the resulting 90% confidence intervals fell between 80% and 125%. Throughout the trial, participants in each group were transitioned to the alternative treatment options, with a washout interval of 7 ± 1 days separating consecutive treatment phases.
Of the 19 patients brought into the trial, two were set aside from the final analysis, leaving 17 whose data could be assessed. When administered under the skin rather than through a vein, furosemide delivered absorption levels that matched intravenous delivery at both injection locations, with the thigh group returning a mean relative bioavailability of 91.3% (90% CI, 86.3–96.6) and the upper arm group recording 92.7% (90% CI, 88.3–97.2).
Uptake into the bloodstream proved slower along the subcutaneous route, while urinary output volumes and the rate at which sodium was expelled remained broadly comparable between treatment groups. Within the first three hours after treatment, both total urine output and the amount of sodium being expelled through urine increased at a noticeable pace, with that upward movement levelling off by roughly the sixth hour.
A second presentation put furosemide 80 mg/10 mL alongside an investigative 80 mg/mL formulation from MannKind, the latter delivered beneath the skin through a single injection lasting five to ten seconds. Two randomized, open-label crossover studies formed the basis of the research, with the first pitting intravenous furosemide against both a 5-hour subcutaneous infusion and a subcutaneous injection.
Two separate arms defined the trial population: one drawing participants who carried New York Heart Association class 2 or 3 heart failure diagnoses and received the treatment by infusion, the other recruiting healthy volunteers for the injection-based protocol. Of the participants enrolled across both arms of the trial, 15 went through the infusion protocol to its end while 19 did the same in the injection arm.
When administered intravenously, peak concentration levels reached approximately four times those observed with subcutaneous delivery under an infusion protocol, and approximately twice as high under an injection protocol, yet total drug exposure across the full concentration-time curve held broadly comparable between routes. Equivalence between the two formulations, in pharmacokinetic terms, was borne out by the data.
Both delivery routes — subcutaneous injection and infusion — prompted urinary flow within the opening hour, though the injection arm produced a noticeably higher volume; measured across the full eight-hour window, total urine output and sodium excretion held at comparable levels across all three arms.
Taken together, the two presentations established that subcutaneous furosemide matches the absorption profile of its intravenous form, while also demonstrating that a range of alternate injection sites can deliver the drug effectively. Okwueze noted that access to multiple administration routes allows patients to rotate sites at will, work around implanted abdominal devices by shifting to the arms or thighs, and benefit from near-complete bioavailability — all of which, in her view, positions the approach as a viable alternative for heart failure patients who cannot achieve adequate diuresis.
