GLP-1 drugs and the kidneys: what FLOW showed

Chronic kidney disease is common in type 2 diabetes and usually silent until late. It is tracked with two numbers on a routine blood and urine test: eGFR, an estimate of how well the kidneys filter, and the urine albumin-to-creatinine ratio (UACR), which measures protein leaking into the urine. A falling eGFR and a rising UACR are what drive kidney failure, dialysis and, in parallel, heart disease.

The question for GLP-1 drugs was whether they slow that process in a way that shows up as fewer hard events. FLOW was built to answer it.

The trials at a glance

Who was in FLOW

FLOW enrolled people with type 2 diabetes and established chronic kidney disease, defined in two ways: an eGFR of 50 to 75 with a UACR above 300 mg/g, or an eGFR of 25 to under 50 with a UACR above 100 mg/g. In plain terms, moderately reduced kidney function with significant protein in the urine. 1,767 were assigned to semaglutide 1 mg weekly, an Ozempic dose, and 1,766 to placebo, on top of standard care.

What FLOW found

The primary end point was a composite of kidney failure (dialysis, transplant or eGFR below 15), a fall in eGFR of at least 50 percent, or death from kidney or cardiovascular causes. An independent committee recommended stopping the trial early at a planned interim analysis, after a median 3.4 years, because the benefit was clear.

• Primary end point: 331 first events on semaglutide against 410 on placebo, a 24 percent lower risk (HR 0.76, 95% CI 0.66 to 0.88).
• Kidney-only components: HR 0.79 (0.66 to 0.94), so the result was not carried by the cardiovascular deaths alone.
• Rate of decline: eGFR fell more slowly on semaglutide, by 1.16 mL/min/1.73 m² per year.
• Cardiovascular death: HR 0.71 (0.56 to 0.89).
• Major cardiovascular events: 18 percent lower (HR 0.82, 0.68 to 0.98).
• Death from any cause: 20 percent lower (HR 0.80, 0.67 to 0.95).

Serious adverse events were reported in fewer people on semaglutide than on placebo, 49.6 against 53.8 percent. That high background rate reflects how unwell this population was, not the drug.

The FDA approval, January 2025

On 28 January 2025 the FDA approved Ozempic to reduce the risk of kidney disease worsening, kidney failure and death from cardiovascular causes in adults with type 2 diabetes and chronic kidney disease. Novo Nordisk described it at the time as the only GLP-1 drug with a kidney indication. The approval sits on top of Ozempic's existing blood sugar and cardiovascular indications. The heart trials page covers the cardiovascular data.

People without diabetes: the SELECT kidney analysis

FLOW only included people with diabetes. The closest evidence for people taking semaglutide for weight comes from SELECT, the cardiovascular trial in 17,604 adults with heart disease and overweight or obesity but no diabetes. A prespecified kidney analysis, published in Nature Medicine in 2024, used a composite of kidney death, starting dialysis, eGFR persistently below 15, a persistent eGFR fall of at least 50 percent, or new heavy protein loss in the urine.

That composite occurred in 1.8 percent on semaglutide 2.4 mg and 2.2 percent on placebo (HR 0.78, 95% CI 0.63 to 0.96). At 104 weeks, eGFR was 0.75 units higher on semaglutide than placebo, and 2.19 units higher in people who started with an eGFR below 60.

Two cautions. This was a secondary analysis of a heart trial, so it supports but does not prove a kidney benefit. And the absolute numbers are small because most SELECT participants had healthy kidneys at the start. The finding is most relevant to people who already have reduced kidney function.

Tirzepatide and the kidneys

Tirzepatide has no dedicated kidney outcome trial published. In SURPASS-CVOT, against dulaglutide, kidney measures favoured tirzepatide, but those comparisons were not controlled for multiple testing and should be read as hypotheses. Until a kidney outcome trial reports, the kidney indication belongs to semaglutide alone.

The other side: dehydration

The labels warn about acute kidney injury, almost always from dehydration after repeated vomiting or diarrhoea. That is a different mechanism from the long-term benefit FLOW measured, and it is preventable. Persistent vomiting is a same-day call; the side effects page has the red flags. People with existing kidney disease have the least reserve, so fluids matter most for them.

What to check

eGFR and UACR are cheap and routine. If you have diabetes, high blood pressure or a family history of kidney disease, a baseline before starting and a repeat at the usual reviews give a trend line. One reading means little; the slope is the point. Note that eGFR is calculated from creatinine, which comes partly from muscle, so large changes in muscle mass can move it. The lean mass page and GLP-1 blood work page cover this, and how to read a lab report explains reference ranges.

For kidney questions the log that helps is eGFR and UACR on the same timeline as the dose, the weight and any bad stretch of vomiting or diarrhoea, so a dip can be matched to what happened that week. The free GLP-1 tracker keeps the dose, the weight, side effects and, on Premium, lab results on one timeline, so the numbers your prescriber asks about are in one place rather than spread across portals and notes. It is free to download.