FLOW: semaglutide had fewer serious adverse events than placebo even below eGFR 30

Design

Prespecified secondary safety analysis of a randomised placebo-controlled trial

Population

3,533 people with type 2 diabetes and CKD in FLOW

Primary outcome

Serious adverse events and discontinuations by baseline eGFR

Effect

SAEs below eGFR 30: 56.4% vs 60.4%; GI discontinuation 4.5% vs 1.1%

A prespecified secondary analysis of the FLOW trial, published in Kidney International on 20 October 2026, reported safety by baseline eGFR in 3,533 people with type 2 diabetes and CKD randomised to semaglutide 1.0 mg weekly or placebo.

Serious adverse events were less frequent with semaglutide in every eGFR group: 45.1% against 50.4% at eGFR 60 or more, and 56.4% against 60.4% below 30. Infections, cardiac, respiratory and metabolic serious events were generally lower with semaglutide. Discontinuation for any adverse event rose as eGFR fell but was similar between arms (18.8% against 18.7% below 30). Discontinuation for gastrointestinal effects was higher with semaglutide, 4.5% against 1.1%.

The analysis is descriptive, without formal testing by subgroup. Its value is reassurance that semaglutide's safety profile does not worsen as kidney function declines within the range FLOW studied, which is where clinicians are most hesitant.

• Do not withhold semaglutide from people with type 2 diabetes and CKD solely because eGFR is below 30, within trial limits.
• Expect gastrointestinal intolerance to be the main reason for stopping; titrate slowly.
• Monitor hydration during gastrointestinal side effects, which can precipitate acute kidney injury.
• Note FLOW did not include people on dialysis.

Why it matters

Low eGFR often stops clinicians starting a GLP-1 receptor agonist; this removes much of that hesitation.

Don't overread it

A descriptive subgroup safety analysis — it was not powered to compare safety between eGFR groups.

The statistics, in plain English

These are numerical comparisons without formal significance tests in each subgroup, so differences of a few percentage points should be read as consistent patterns rather than proven effects.

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