FLOW results show injectable semaglutide 1 mg slowed kidney disease progression

Injectable semaglutide 1 mg slowed the progression of chronic kidney disease in people with type 2 diabetes, according to FLOW trial results described in a review of semaglutide cardiovascular outcomes published by DiabetesontheNet ^[2]. In FLOW, the composite kidney outcome was significantly better in people taking semaglutide than in those taking placebo, with a hazard ratio of 0.76 — a 24% relative reduction in the risk of that combined measure ^[2]. The FLOW results appeared in the New England Journal of Medicine in 2024 ^[2].

The number of people enrolled in FLOW, the exact parts of its composite kidney endpoint, the length of follow-up and the absolute difference in event rates between the two groups have not been reported in the material available.

The same review also describes SOUL, a cardiovascular outcomes trial of oral semaglutide taken once daily at doses up to 14 mg, published in the New England Journal of Medicine ^[2]. SOUL enrolled 9,650 people aged 50 or older with type 2 diabetes at high cardiovascular risk and followed them for a median of about four years; the article gives 48 months in one place and 49.5 months in another ^[2]. The primary outcome — cardiovascular death, non-fatal heart attack or non-fatal stroke — occurred in 12.0% of the oral semaglutide group and 13.8% of the placebo group, a hazard ratio of 0.86 (95% CI 0.77–0.96; P=0.006), a 14% relative reduction driven largely by fewer non-fatal heart attacks ^[2].

The kidney picture in SOUL was different. The first confirmatory secondary outcome, a composite of major kidney disease events, did not differ between the oral semaglutide and placebo groups, and statistical testing stopped at that point ^[2]. The review notes that the trial authors proposed several possible explanations: participants in SOUL had higher kidney function at the start, the oral form has lower bioavailability, or the difference was due to chance ^[2].

Other SOUL results: average weight loss was 4.22 kg with oral semaglutide versus 1.27 kg with placebo, and HbA1c fell by 0.71 percentage points (7.8 mmol/mol), 0.56 percentage points more than placebo ^[2]. Gastrointestinal side effects were reported in 5.0% of the semaglutide group and 4.4% of the placebo group; serious adverse events occurred in about half of each group; 27% of those taking semaglutide and 28.5% of those taking placebo stopped treatment because of side effects ^[2]. The SOUL population was 70% people with coronary artery disease, 23% with heart failure, 21% with cerebrovascular disease and 16% with peripheral artery disease; 28.9% were women and 2.6% were Black ^[2]. The review cautions that these results may not apply directly to lower-risk patients with type 2 diabetes ^[2].

Why it matters for patients

Kidney protection is a separate question from blood sugar and weight, and the evidence now differs by how semaglutide is given. For people with type 2 diabetes and chronic kidney disease, the injectable 1 mg dose studied in FLOW carries a demonstrated kidney benefit, while oral semaglutide did not show one in SOUL ^[2]. The review states that the FLOW kidney result cannot be extrapolated to the oral form, because the two trials enrolled different populations and tested different primary outcomes ^[2].

SOUL does add reassurance on the heart side: in people with type 2 diabetes and established cardiovascular disease, chronic kidney disease, or both, daily oral semaglutide reduced major cardiovascular events, similar to what has been seen with the injectable form ^[2]. The review notes that oral semaglutide has to be taken exactly as directed for its effects on blood sugar, weight and cardiovascular outcomes to show up ^[2].

What is not established: whether semaglutide affects kidney outcomes in people who do not have type 2 diabetes, or at doses other than those studied, has not been reported. No regulatory decisions about changing product labels based on these results have been disclosed.