Diabetes medicines that help the kidneys also reduced kidney disease progression in trial patients without diabetes.

Do kidney-protection results from diabetes drug trials apply when diabetes is absent? That has been hard to answer because most earlier trial evidence came mainly from people with diabetes. This analysis combined the results of 13 large double-blind, placebo-controlled SGLT2 inhibitor trials, and split them by whether participants had diabetes. The overall group included people with type 2 diabetes at high cardiovascular risk, while the people without diabetes were enrolled in trials of chronic kidney disease or heart failure. In other words, this is not a study of healthy adults.

The medicines are called SGLT2 inhibitors; they help the kidneys pass excess blood glucose into the urine. In each included trial, participants were randomly assigned to one of these medicines or a dummy placebo, and then followed for at least six months. The researchers grouped participants by diabetes status and pooled the results using a standard method called meta-analysis.

For the main kidney outcome, allocation to an SGLT2 inhibitor reduced the risk of kidney disease progression by 37% overall compared with placebo. The benefit was similar in people with diabetes and in those without diabetes; in people without diabetes, the relative risk was 0.69 (95% CI 0.57–0.82), which means about a 31% lower risk, and in people with diabetes it was 0.62. Across the four chronic kidney disease trials, the reduction was also similar regardless of the underlying kidney diagnosis.

That outcome was not a mild lab change. Kidney disease progression was defined as a sustained loss of at least half of kidney filtration, a sustained very low level of kidney function, end-stage kidney disease, or death from kidney failure. Translating the relative result into absolute terms: for every 1,000 patients with chronic kidney disease treated for one year, the estimates suggest 11 first progression events would be avoided in those with diabetes and 15 fewer patients with kidney disease progression among those without diabetes. SGLT2 inhibitors also reduced acute kidney injury by 23% overall, again with similar effects in both groups.

Harms were uncommon but real. In people with diabetes, the absolute risk of ketoacidosis was low—around 0.2 events per 1,000 patient-years in the placebo groups—and allocation to an SGLT2 inhibitor was linked to roughly double that rate. Among people without diabetes receiving an SGLT2 inhibitor, only one ketoacidosis event was recorded during about 30,000 participant-years of follow-up. Lower limb amputation was also prespecified as a safety outcome, and in the studied patients with chronic kidney disease without diabetes, no excess risk of ketoacidosis or amputation was seen. Overall, the researchers estimated that the absolute benefits outweighed the serious hazards in these trial populations.

The scope is important. These findings apply to people who were already at elevated risk because of chronic kidney disease, heart failure, or type 2 diabetes with high cardiovascular risk, not to healthy adults seeking prevention. Evidence remains thin for type 1 diabetes, polycystic kidney disease, and people already on dialysis or with a kidney transplant. Absolute numbers also came from the studied trial populations, so an individual's benefit will depend on their starting risk.