There have been efforts to investigate the use of SGLT2i in the prevention of kidney stones. For quite a while there were no dedicated trials with clear outcomes for a wide variety of patients, although there were hints that SGLT2i might lower the odds of kidney stones in both diabetics and non-diabetics, particularly in men. I list some overviews and studies below. However, a big study - SWEETSTONE - that was focused on this question has been finally published and it is looking very good indeed for empagliflozin.
Previously:
Inhibition of sodium-glucose cotransporter 2 suppresses renal stone formation
https://www.sciencedirect.com/science/article/pii/S1043661822004704?via%3Dihub
" Conclusion
Overall, our findings identified that SGLT2 inhibition prevents renal stone formation and may be a promising therapeutic approach against nephrolithiasis."
SGLT2 Inhibitors and Their Effect on Urolithiasis: Current Evidence and Future Directions
" In conclusion, UL has become more common worldwide, partly due to rising rates of CRM diseases, which are bidirectionally related to stone formation. SGLT2 inhibitors may help reduce UL risk, particularly in patients with diabetes. However, these inhibitors also pose a potential risk for increased uric acid stone formation. The SWEETSTONE trial, focusing on patients who form stones, will further explore the effectiveness of SGLT2 inhibitors in preventing recurrent kidney stones and their impact on urinary chemistry [60]. Understanding the effects of these medications is key to optimizing treatment and preventing UL complications."
Sodium-glucose cotranspor ter 2 (SGLT2) inhibitors in nephrolithiasis: should we “gliflozin” patients with kidney stone disease?
“Nephrolithiasis is a global healthcare problem in almost all developed and developing countries. Its prevalence has increased, with a high recurrence rate. Despite advances in understanding lithiasis disease, it is crucial to develop effective strategies to prevent nephrolithiasis, an unmet need. Although preliminary results with iSGLT2 are encouraging, this hypothesis needs to be tested in lithiasis patients, primarily aiming to reduce urinary stones. Pending the results of randomized clinical trials, one approach to be adopted at this time would be to associate gliflozins to the treatment of lithiasis patients with already established indications for these medications, such as in concomitant diabetic kidney disease, for instance.”
And finally, we have the long awaited SWEETSTONE study:
Empagliflozin in nondiabetic individuals with calcium and uric acid kidney stones: a randomized phase 2 trial
https://www.nature.com/articles/s41591-024-03330-x
Quote:
“In SWEETSTONE, empagliflozin treatment was associated with a 36% reduction of RSR CaP in patients with calcium stones, and a 30% reduction of RSR UA in patients with UA stones compared with placebo. In a pooled analysis of phase 1–4 trials in patients with T2D, empagliflozin treatment was associated with a 36% risk reduction of incident kidney stone events14. In large cohort studies of patients with T2D, risk reductions of 26–49% for incident kidney stone events were reported with SGLT2 use11,13. Considering the correlation of RSR decreases with reductions in recurrent stone events reported previously, we anticipate that the beneficial changes in RSRs observed with empagliflozin in SWEETSTONE will translate into a similar decrease in recurrent stone events in nondiabetic kidney SFs, as has been observed in patients with T2D.”
To sum up, it looks like SGLT2i can have a good impact on the likelyhood of developing kidney stones, whether you’re diabetic or not. This is certainly good news, and should ameliorate some of the concerns around taking these drugs by folks in our group, who generally are not diabetic. Kidney stone formation seems to have a genetic component, so anything that can help here is something to be glad about.
