Sodium-glucose cotransporter 2 inhibitors and risk of nephrolithiasis

Diabetologia. 2021 Jul;64(7):1563-1571. doi: 10.1007/s00125-021-05424-4. Epub 2021 Mar 13.


Aims/hypothesis: Sodium-glucose cotransporter 2 inhibitors (SGLT2Is) may reduce nephrolithiasis risk by increasing urine flow. We aimed to investigate whether initiation of SGLT2I was associated with reduced nephrolithiasis risk.

Methods: We conducted an active-comparator new-user cohort study using the Danish health registries in the period 11 November 2012 to 31 December 2018. Individuals aged ≥40 years initiating SGLT2Is or glucagon-like peptide-1 receptor agonists (GLP1 RAs) were followed from treatment initiation until an inpatient or outpatient diagnosis of nephrolithiasis, death, emigration or end of study. New users of SGLT2Is were matched 1:1 on propensity scores to new users of GLP1 RAs. In supplementary analyses, risk of recurrent nephrolithiasis was assessed in individuals with a history of nephrolithiasis before treatment initiation.

Results: We identified 24,290 and 19,576 eligible users of SGLT2Is and GLP1 RAs, respectively. After matching, 12,325 patient pairs remained. The median age was 61 years and median follow-up was 2.0 years. The nephrolithiasis rate was 2.0 per 1000 person-years in SGLT2I initiators compared with 4.0 per 1000 person-years in GLP1 RA initiators, with a rate difference of -1.9 per 1000 person-years (95% CI -2.8, -1.0) and an HR of 0.51 (95% CI 0.37, 0.71). For recurrent nephrolithiasis (n = 731 patient pairs), the rate difference was -17 per 1000 person-years (95% CI -33, -1.5) and the HR was 0.68 (95% CI 0.48, 0.97).

Conclusions/interpretation: Initiation of treatment with SGLT2Is was associated with a clinically significant reduced risk of incident and recurrent nephrolithiasis.

Keywords: Cohort studies; Databases; Dipeptidyl peptidase 4 inhibitors; Glucagon–like peptide 1 receptor agonists; Nephrolithiasis; Observational studies; Sodium–glucose cotransporter 2 inhibitors; Type 2 diabetes.