Some Diabetes Drugs Linked to Lower Kidney Disease and Gout Risk

Use of sodium glucose cotransporter 2 (SGLT-2) inhibitor drugs to treat type 2 diabetes may also help to lower the risk of recurrent kidney stones and gout flare-ups, finds a study from Canada published by The BMJ today.

Kidney stones (nephrolithiasis) and gout are both common, recurrent, extremely painful conditions, especially in patients with type 2 diabetes. They also incur substantial healthcare costs.

As well as treating type 2 diabetes, trials have shown that SGLT-2 inhibitors can also lower the risk of heart failure and kidney disease, but their effect on recurrent kidney stones and gout flare-ups is still uncertain.

To explore this further, researchers set out to compare the effects of SGLT-2 inhibitors on risk of recurrent kidney stones and gout with two other groups of diabetes drugs known as GLP-1 receptor agonists and DPP-4 inhibitors.

Their findings are based on data for 20,146 adults (average age 65; 73% men) with type 2 diabetes and a history of kidney stones, gout, or both, who had not previously used SGLT-2 inhibitors, GLP-1 receptor agonists or DPP-4 inhibitors.

A statistical technique called inverse probability weighting was used to remove the influence of other factors, such as patient age, sex, socioeconomic status, time since diabetes diagnosis, other conditions, and drug use.

Hospital and outpatient records were used to track rates of kidney stones and gout flare-ups over an average of 1.3 years for those starting an SGLT-2 inhibitor and 0.93 years for those starting an GLP-1 receptor agonist.

The researchers found a 33% lower recurrence rate of kidney stones among patients starting an SGLT-2 inhibitor compared with a GLP-1 receptor agonist.

This benefit corresponded to 51 fewer active cases of kidney stones per 1,000 person years overall, and 219 fewer cases per 1,000 person years among those with recently active kidney stones. A similar reduction was seen among patients who also had gout.

One explanation is that SGLT-2 inhibitors increase urinary volume and lower uric acid levels in the blood, thus reducing the concentration of stone forming crystals.

Benefits also persisted after further analyses, including among those taking thiazide diuretics (drugs that can increase risk of gout) and those needing hospital treatment for kidney stones, supporting the strength of the findings.

The researchers acknowledge that these are observational findings, so no firm conclusions can be drawn about causality, and they can’t rule out the possibility that other unmeasured factors may have affected their results.

However, they point out that their study design reduces the biases common to observational studies and the findings are likely to be generalisable to wider populations.

As such, they conclude that, for patients with type 2 diabetes, heart failure, or chronic kidney disease, an SGLT-2 inhibitor may be a useful addition to current treatments to simultaneously tackle kidney stones and other conditions, including gout.

Reference: McCormick N, Yokose C, Lu N, et al. Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors for recurrent nephrolithiasis among patients with pre-existing nephrolithiasis or gout: target trial emulation studies. BMJ. 2024;387:e080035. doi: 10.1136/bmj-2024-080035

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