SGLT-2 Inhibitors May be Beneficial in People With Kidney Stones and Gout

Natalie McCormick, PhD

Credit: Massachusetts General Hospital

SGLT-2 inhibitors may be a beneficial addition to treatment regimens in patients with nephrolithiasis (kidney stone) recurrence and comorbidities, including gout, according to new research.¹

Natalie McCormick, PhD, instructor in medicine, Rheumatology and Allergy Clinical Epidemiology Research Center, Massachusetts General Hospital, Boston, and colleagues conducted a target trial emulation including 20,146 patients with nephrolithiasis and type 2 diabetes, including those with concomitant gout at baseline, a high-risk group.

“McCormick and colleagues’ study strengthens the evidence supporting use of SGLT-2 inhibitors for patients with recurrent nephrolithiasis, type 2 diabetes, and comorbidities such as gout. Further research to identify underlying mechanisms of action, and to evaluate use for patients without type 2 diabetes, would help strengthen the evidence still further,” Khashayar Sakhaee, MD, professor, UT Southwestern Medical Center, Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, Dallas, Texas, wrote in a related editorial.²

The investigators found that after inverse probability of treatment weighting, 1924 recurrent nephrolithiasis events occurred among the 14,456 weighted patients who used an SGLT-2 inhibitor (105.3 per 1000 person years), compared with 853 events among the 5877 weighted patients who used a GLP-1 receptor agonist (156.4 per 1000 person years). The adjusted rate ratio of these events was 0.67 (95% CI, 0.57-0.79) and rate difference was −51 (95% CI, −63 to −40) per 1000 person years, with a number needed to treat (NNT) of 20.¹

In participants with recently active nephrolithiasis, the absolute rate difference was 219 per 1000 person years (NNT of 5). The protective associations of SLGT-2 inhibitors remained for nephrolithiasis events that required emergency department visits, hospital admissions, or procedures, and in comparing an SGLT-2 inhibitor with a DPP-4 inhibitor (rate ratio 0.73 [95% CI, 0.68-0.78]),with a rate difference of −38 (95% CI, −46 to −29) per 1000 person years (NNT of 26).¹

Patients with nephrolithiasis and concomitant gout also experienced protective associations with SLGT-2 inhibitors, with a rate ratio of 0.67 (95% CI, 0.57 to 0.79) and rate difference of –53 (95% CI, –78 to –27) per 1000 person years versus a GLP-1 receptor agonist (NNT of 19), and a rate ratio of 0.63 (95% CI, 0.55-0.72) and rate difference of –62 (–81 to –42) per 1000 person years compared with a DPP-4 inhibitor (NNT of 16).¹

McCormick and colleagues also found that SGLT-2 inhibitor use was associated with a lower rate of gout flare-ups (rate ratio, 0.72 [95% CI, 0.54 to 0.95]; rate difference, –16 [95% CI, –31 to –1] per 1000 person years) compared with GLP-1 receptor agonists (0.65, 0.52 to 0.82, and –21, –33 to –9 per 1000 person years) compared with DPP-4 inhibitors. Participants initiating SGLT-2 inhibitors had a higher risk of genital infection (hazard ratio [HR], 2.21 [95% CI, 1.68 to 2.90]; rate difference, 13 per 1000 person years), but no altered risk of osteoarthritis (HR, 0.87 [95% CI, 0.68 to 1.1], and –2 per 1000 person years) or appendicitis encounters (HR, 1.07 [95% CI, 0.69-1.67], and 1 per 1000 person years). Propensity score weighting reinforced these findings.¹

“To answer [remaining questions about SGLT-2 inhibitor mechanisms], a short term proof of concept study followed by long term prospective clinical trials would be of value to patients, clinicians, and researchers. These studies could explore the underlying metabolic factors influencing the formation of kidney stones and inform the development of more targeted treatments. Future studies should also recruit patients with nephrolithiasis but no concurrent diabetes to test whether SGLT-2 inhibitors could be beneficial for them,” Sakhaee wrote.²

REFERENCES
1. McCormick N, Yokose C, Lu N, et al. Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors for recurrentnephrolithiasisamong patients withpre-existingnephrolithiasis or gout:target trial emulationstudies. BMJ. Published online October 30, 2024. doi.org/10.1136/bmj-2024-080035

2. Sakhaee K. SGLT-2 inhibitors for the prevention of recurrent nephrolithiasis BMJ 2024; 387 :q2447 doi:10.1136/bmj.q2447