FLOW: semaglutide and kidney outcomes in type 2 diabetes

Type 2 diabetes with chronic kidney disease carries a high risk of kidney failure, heart events and death. FLOW asked whether the GLP-1 drug semaglutide changes that risk. Over a median 3.4 years, major kidney disease events were 24% less likely on semaglutide than on placebo [1].

Why this study matters

Most of our semaglutide coverage concerns weight, such as STEP 1. FLOW is a different question. Its participants were chosen for kidney disease, and its main outcome was kidney and cardiovascular events rather than body weight. The wider record is in the semaglutide evidence guide.

What they did

Kidney disease was defined in two ways. One was an estimated glomerular filtration rate (eGFR) of 50 to 75 ml per minute per 1.73 m² with a urinary albumin-to-creatinine ratio above 300 and below 5000. The other was an eGFR of 25 to under 50 with a ratio above 100 and below 5000 [1].

The design paper describes FLOW as a randomised, double-blind, parallel-group, multinational phase 3b trial, in which participants were randomised 1:1 and also received renin-angiotensin-aldosterone system blockade unless it was not tolerated or was contraindicated [2]. At baseline the average participant was 66.6 years old, had lived with diabetes for 17.4 years, had a mean HbA1c of 7.8% and a mean eGFR of 47.0, and 68.2% were at very high risk of kidney disease progression by international guideline categories [2]. In other words, this was an older group with long-standing, established disease, not people with early or mild kidney changes.

The primary outcome was a composite called major kidney disease events. It counted kidney failure (dialysis, transplantation, or an eGFR below 15), at least a 50% fall in eGFR from baseline, or death from kidney-related or cardiovascular causes. Confirmatory secondary outcomes were tested in a prespecified order [1].

What they found

Every confirmatory secondary outcome favoured semaglutide [1]. Two points about reading the table. First, the eGFR slope, major cardiovascular events and all-cause death were the confirmatory secondary outcomes, and the abstract reports cardiovascular death separately alongside the kidney-specific components [1]. Second, the eGFR slope result is an average rate of decline, not a restoration of kidney function: semaglutide slowed the average decline by 1.16 ml per minute per 1.73 m² each year compared with placebo [1].

A hazard ratio of 0.76 means the rate of first events was about a quarter lower in the semaglutide group at any point in follow-up. It does not mean a quarter of people avoided kidney failure.

Safety reported

Serious adverse events were reported by 49.6% of the semaglutide group and 53.8% of the placebo group [1]. That is a small gap: roughly half of both groups had a serious event. The abstract we checked does not give rates for individual side effects, so this article makes no claim about nausea, vomiting or other specific events. They are covered in the full paper, and for the same drug at a different dose in our STEP 8 breakdown.

Caveats

• Sponsor. Novo Nordisk, which makes semaglutide, funded FLOW, and several authors are company employees [1].
• Early stopping. The trial ended early on a prespecified interim analysis recommendation. Trials stopped early can overstate effects, so the size of the benefit is best read as an estimate, though the direction was consistent across outcomes [1].
• One population. Everyone had type 2 diabetes and chronic kidney disease within set eGFR and albumin ranges. The result does not extend to people without diabetes, to earlier or more advanced kidney disease, or to other causes of kidney damage [1].
• One dose against placebo. The comparison was semaglutide 1.0 mg weekly against placebo. FLOW does not show how semaglutide compares with other kidney-protective medicines [1].
• Composite outcome. The primary outcome bundled several events. The kidney-specific components alone gave a smaller effect (hazard ratio 0.79) than the combined measure [1].
• Human trial only. Everything above comes from people. It says nothing about animal studies or unregulated products.

What it means in practice

FLOW describes what happened to a defined group of patients treated under medical supervision. It is not a recommendation to use semaglutide or any medicine, and it is not guidance for people who do not have this condition. Kidney disease treatment depends on individual kidney function, other medicines, and risks that belong with a clinician.

What is still open

• How the benefit compares with, or adds to, other kidney-protective treatments.
• Whether the effect holds over longer follow-up, and what happens after treatment stops.
• Whether people without diabetes who have kidney disease would see a similar effect.
• How individual side effects, as listed in the full paper, weigh against the benefit for different patients.

What this means

We read FLOW as showing that, in adults with type 2 diabetes and chronic kidney disease, weekly semaglutide reduced the rate of major kidney disease events and cardiovascular death compared with placebo over about 3.4 years [1]. The sponsor is the manufacturer, and the trial stopped early. To argue the benefit is smaller than reported you would need longer or independent follow-up, and the consistent direction across every confirmatory outcome makes that a harder case.

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