SGLT2 drugs slow kidney disease and cut heart events — with or without diabetes

The class of drugs known as SGLT2 inhibitors — dapagliflozin, empagliflozin and their siblings — began as diabetes medicines, but the large trials now show they slow the progression of chronic kidney disease and cut cardiovascular events in people who do not have diabetes as well as those who do [s1]. That generalisation beyond diabetes is the finding that has reshaped how kidney and heart disease are treated.

What the pooled evidence shows

The strongest single answer comes from a collaborative meta-analysis in The Lancet that pooled 13 placebo-controlled trials involving 90,409 analysed participants [s1]. Most had diabetes — 74,804, or 82.7% — but 15,605 (17.3%) did not, which is what allowed the researchers to test whether the benefit depended on diabetes [s1].

It largely did not. Compared with placebo, SGLT2 inhibitors reduced the risk of kidney disease progression by 37% (relative risk 0.63, 95% confidence interval 0.58 to 0.69), with similar relative risks in participants with and without diabetes [s1]. They reduced acute kidney injury by 23% (RR 0.77, 0.70 to 0.84) and the composite of cardiovascular death or hospitalisation for heart failure by 23% (RR 0.77, 0.74 to 0.81) — again with similar effects regardless of diabetes status [s1]. They also reduced cardiovascular death specifically (RR 0.86, 0.81 to 0.92), though not non-cardiovascular death (RR 0.94, 0.88 to 1.02) [s1].

The trial that opened the question

The meta-analysis rests in part on DAPA-CKD, published in the New England Journal of Medicine, which was designed explicitly to include people with chronic kidney disease with or without type 2 diabetes [s2]. It randomised 4,304 people with reduced kidney function and protein in the urine to dapagliflozin 10 mg daily or placebo [s2]. Over a median of 2.4 years, the primary outcome — a composite of a sustained 50% or greater decline in kidney filtration, end-stage kidney disease, or death from kidney or cardiovascular causes — occurred in 9.2% of the dapagliflozin group versus 14.5% of the placebo group (hazard ratio 0.61, 95% CI 0.51 to 0.72; P < 0.001) [s2]. The trial reported a number needed to treat of 19 to prevent one primary event [s2]; the independent monitoring committee stopped it early for efficacy [s2]. The purely kidney-focused composite — a sustained 50% or greater fall in filtration, end-stage kidney disease, or death from kidney causes — was reduced with a hazard ratio of 0.56 (95% CI 0.45 to 0.68) [s2].

A second dedicated kidney trial, EMPA-KIDNEY, extended the picture to a broader range of chronic kidney disease. Published in the New England Journal of Medicine, it randomised 6,609 patients — including people with lower filtration rates and a wider spread of underlying diagnoses — to empagliflozin 10 mg daily or placebo [s3]. Over a median of 2.0 years, the primary outcome of kidney disease progression or cardiovascular death occurred in 13.1% of the empagliflozin group versus 16.9% on placebo (hazard ratio 0.72, 95% confidence interval 0.64 to 0.82) [s3]. Together, the two trials and the pooled analysis point the same way: the benefit is a property of the drug class acting on the kidney and heart, not a side effect of treating diabetes.

The limits worth stating

These are strong trials, but a few things bound the claim. The meta-analysis notes that none of the trials recruiting people with and without diabetes was originally designed to assess outcomes separately in those without diabetes — so the equal benefit across groups is a robust pooled inference rather than the result each trial was individually powered to prove [s1]. The trials also enrolled people at elevated risk — established kidney disease, heart failure, or high cardiovascular risk — not the general population, so the numbers describe benefit in those groups, not a preventive effect in otherwise healthy people [s1] [s2]. And these are prescription drugs with their own safety profile, including specific risks the trials tracked such as diabetic ketoacidosis, which is why they are started and monitored by a clinician.

What this leaves a reader with

The evidence establishes something genuinely new: a drug class born for blood sugar turns out to protect the kidneys and heart through mechanisms that do not depend on diabetes, with consistent benefit in people who never had it [s1] [s2]. Whether an individual is a candidate depends on their kidney function, protein levels, heart history and other medicines — a decision that sits with a clinician, not a lab value alone.

This article is informational and is not medical advice.

Sources

• Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials — The Lancet, 2022-11-06
• Dapagliflozin in Patients with Chronic Kidney Disease — New England Journal of Medicine, 2020-09-24