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.
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Journal
The BMJ
Method of Research
Observational study
Subject of Research
People
Article Title
Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors for recurrent nephrolithiasis among patients with pre-existing nephrolithiasis or gout: emulation of two target trials
Article Publication Date
30-Oct-2024
COI Statement
All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the National Institutes of Health and Canadian Institutes of Health Research; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. DW reports serving on data monitoring committees for Novo Nordisk, not related to the topic of this work. RM has received support from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (NIH), National Institute on Aging of the NIH, Patient Centered Outcomes Research Institute, National Center for Advancing Translational Sciences, and the American Diabetes Association. She also serves as a consultant to Emmi (Wolters Kluwer) on developing patient education materials related to diabetes, and to Yale-New Haven Health System’s Center For Outcomes Research and Evaluation on developing quality measures related to diabetes. GCC is the Chief Medical Officer at OM1 and reports research support from GSK. HKC reports research support from Horizon, and consulting fees from Ani, LG, Horizon, Shanton, and Protalix