This study aimed to build upon prior research that examined the relationship between oral hypoglycemics and stone recurrence, particularly findings that suggested a modest reduction in risk with SGLT-2 inhibitors.6 Specifically, we evaluated the potential impact of metformin on stone formation among diabetic patients given its place as a first-line, low-cost treatment for type 2 diabetes.7 Preclinical studies have indicated that metformin may exert protective effects against calcium oxalate stone formation through various mechanisms.8-10 We sought to determine whether these bench-top findings could be corroborated clinically.
We performed a retrospective cohort analysis of diabetic patients with a history of recurrent urolithiasis. Patients were included if they had initiated metformin therapy between two 24-hour urine collections, allowing us to isolate the drug’s effect on urinary parameters. To minimize confounding variables, we excluded individuals taking other diabetic medications or urine-altering agents during this period. This design allowed us to use each patient as their own control, thereby augmenting the power of analysis.
Among the 427 patients in our cohort, we observed no significant change in key urinary parameters, including but not limited to supersaturation of calcium oxalate, supersaturation of calcium phosphate, and supersaturation of uric acid. These findings held true regardless of metformin dosage or duration of use prior to the second 24-hour urine collection.
Our findings serve to reinforce the importance of adhering to established dietary and hydration guidelines for stone prevention among newly diagnosed diabetic patients without a history of urolithiasis. Among these individuals, we recommend metformin as a safe first-line therapy due to the absence of adverse effects of this drug on key urinary parameters. For diabetic patients with a history of urolithiasis or who have developed urolithiasis during metformin therapy, an SGLT-2 inhibitor should be considered, given its potential dual benefits for addressing both glucose control and urolithiasis prevention.
Written by: Taylor Crook and Ralph V. Clayman
- Department of Urology, School of Medicine, University of California, Irvine, CA, USA
- Pearle MS, Goldfarb DS, Assimos DG et al. Medical management of kidney stones: AUA guideline. J Urol. (2014) https://doi.org/10.1016/j.juro.2014.05.006
- Almuhanna NR, Alhussain AM, Aldamanhori RB et al. Association of chronic hyperglycemia with the risk of urolithiasis. Cureus. (2023) https://doi.org/10.7759/cureus.47385
- Taylor EN, Stampfer MJ, Curhan GC. Diabetes mellitus and the risk of nephrolithiasis. Kidney Int. (2005) https://doi.org/10.1111/j.1523-1755.2005.00516.x
- Zimmerer T, Weiss C, Hammes HP. Evaluation of urolithiasis: a link between stone formation and diabetes mellitus? Urol Int. (2009) https://doi.org/10.1159/000209371
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- Paik JM, Tesfaye H, Curhan GC, Zakoul H, Wexler DJ, Patorno E. Sodium-glucose cotransporter 2 inhibitors and nephrolithiasis risk in patients with type 2 diabetes. JAMA Intern Med. (2024) https://doi.org/10.1001/jamainternmed.2023.7660
- The Top 300 of (2023) https://clincalc.com/DrugStats/Top300Drugs.aspx Accessed 30 August 2025
- Yang X, Yang T, Li J et al. Metformin prevents nephrolithiasis formation by inhibiting the expression of OPN and MCP-1 in vitro and in vivo. Int J Mol Med. (2019) https://doi.org/10.3892/ijmm.2019.4084
- Liu H, Duan C, Yang X et al. Metformin suppresses calcium oxalate crystal-induced kidney injury by promoting Sirt1 and M2 macrophage-mediated anti-inflammatory activation. Sig Transduct Target Ther. (2023) https://doi.org/10.1038/s41392-022-01232-3
- Zhang X, Liang F, Li T, Jiang Y, Ren F. Metformin ameliorates calcium oxalate crystallization and stone formation by activating the Nrf2/HO-1 signaling pathway: two birds with one stone. Arch Biochem Biophys. (2023) https://doi.org/10.1016/j.abb.2023.109568