Semaglutide lowers risk of kidney failure and cardiovascular death in patients with type 2 diabetes and CKD, study results show

Semaglutide can reduce the risk of clinically important kidney outcomes and death from cardiovascular causes in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD), study results have revealed.

The Novo Nordisk-funded ‘FLOW’ trial, published in the New England Journal of Medicine on 24 May 2024, randomly assigned patients with T2DM and CKD to receive subcutaneous semaglutide at a dose of 1.0mg weekly, or a placebo, to test whether treatment with semaglutide would mitigate the high risk for kidney failure, cardiovascular events and death.

The 3,533 adults from 387 sites in 28 countries, including the UK, who underwent randomisation — 1,767 in the semaglutide group and 1,766 in the placebo group — were followed up after a median of 3.4 years.

The primary outcome was defined in the study abstract as “major kidney disease events, a composite of the onset of kidney failure… at least a 50% reduction in the estimated glomerular filtration rate from baseline, or death from kidney-related or cardiovascular causes”.

Results showed that the risk of a primary-outcome event was 24% lower in the semaglutide group than in the placebo group (331 versus 410 first events; hazard ratio, 0.76; 95% confidence interval [CI], 0.66–0.88; P=0.0003).

The results were similar for a composite of the kidney-specific components of the primary outcome (hazard ratio, 0.79; 95% CI, 0.66–0.94) and for death from cardiovascular causes (hazard ratio, 0.71; 95% CI, 0.56–0.89).

In addition, serious adverse events were reported in a slightly lower percentage of participants in the semaglutide group than in the placebo group (49.6% vs. 53.8%).

The study’s authors concluded: “Semaglutide reduced the risk of clinically important kidney outcomes and death from cardiovascular causes in patients with T2DM and CKD.”

Commenting on the trial, Clare Morlidge, a consultant renal pharmacist and deputy chair of the UK Renal Pharmacy Group, said: “CKD is predicted to be the fifth largest cause of mortality by 2040 and so slowing progression of CKD and reducing cardiovascular mortality will reduce NHS spend and is hugely important for patients.

“This is a really important trial in patients with T2DM, and will be another medication in the cupboard for slowing the progression of CKD.

“Its use alongside ACEi/ARB, SGLT2 inhibitors and mineralocorticoid antagonists will help form the pillars of treatment for delaying the progression of CKD and reducing cardiovascular mortality.”

Aisling McMahon, executive director of research at Kidney Research UK, said: “The results of the FLOW trial indicate semaglutide could improve quality of life for patients living with diabetes and CKD because they might be able to delay or avoid needing dialysis or transplantation, but importantly, it also showed that it reduced the risk of death from any cause.

“Hopefully this is just the beginning — we would love to see further research involving patients with non-diabetic chronic kidney disease who may benefit from this.”