No New Semaglutide Safety Concerns in Type 2 Diabetes and CKD

Serious adverse events (SAEs) were reported less frequently with semaglutide than placebo across baseline estimated glomerular filtration rate (eGFR) subgroups in people with type 2 diabetes (T2D) and chronic kidney disease (CKD), according to a prespecified secondary analysis of the Evaluate Renal Function With Semaglutide Once Weekly (FLOW)  trial published in Kidney International.

The investigators noted that people with T2D and CKD often experience medication intolerance and adverse effects (AEs) that worsen with lower eGFR, and that a comprehensive safety assessment was needed to establish whether semaglutide’s benefit-risk profile extends across eGFR levels.

FLOW was a double-blind, randomized, placebo-controlled trial of subcutaneous semaglutide 1.0mg once weekly or placebo, added to standard of care, in 3,533 adults with T2D and CKD. This descriptive analysis reported investigator-reported safety data by baseline eGFR. Over a median follow-up of 3.4 years, SAEs occurred in 45.1% of semaglutide recipients and 50.4% of placebo recipients with an eGFR of 60mL/min/1.73m² or higher, and in 56.4% and 60.4%, respectively, with an eGFR below 30mL/min/1.73m².

Treatment discontinuations due to AEs rose with lower baseline eGFR in both groups, from 11.2% with semaglutide and 11.3% with placebo in the highest eGFR subgroup to 18.8% and 18.7%, respectively, in the lowest. Discontinuations due to gastrointestinal AEs were more frequent with semaglutide (4.5%) than placebo (1.1%), and in the lowest eGFR subgroup, gastrointestinal SAEs occurred in 9.6% and 3.3%, respectively. The investigators reported that frequencies of prespecified AEs of special interest, including acute kidney injury, were similar between groups. Severe hypoglycemia was rare, and no cases of medullary thyroid carcinoma were reported.

The authors concluded that no new safety concerns emerged, including in participants with the lowest baseline eGFR. They noted that the analysis was descriptive and not designed for statistical assessment by eGFR, that nonserious AEs were not systematically collected, and that the median 3.4-year duration was relatively short.

Source: Tuttle KR, Andersen MR, Arici M, et al. Safety outcomes of semaglutide by chronic kidney disease severity in the FLOW trial. Kidney Int. Published online October 20, 2026. doi:10.1016/j.kint.2026.09.026