Postdoctoral Researcher Pharmacoepidemiology Group, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich Zurich, Switzerland
Background: Nephrolithiasis, or kidney stones, is a common complication of type 2 diabetes mellitus (T2DM), and the incidence has increased over the last decades. Previous evidence has suggested that sodium-glucose cotransporter 2 inhibitors (SGLT2i) might reduce the risk of nephrolithiasis.
Objectives: To investigate the risk of nephrolithiasis in patients with T2DM taking SGLT2i compared to glucagon-like peptide 1 receptor agonists (GLP1 RA), using a large electronic health records (EHR) database of primary care data in the UK.
Methods: We conducted an active comparator, new user cohort study. We used the IQVIA Medical Research Data (IMRD) that incorporates data supplied from THIN, a Cegedim database. Reference made to THIN is intended to be descriptive of the data asset licensed by IQVIA. The data consisted of anonymized EHR generated from the daily record of General Practitioners (GPs) between January 1st 2006 to 30th September 2022. The exposure was defined as the first use of SGLT2i compared to GLP1 RA in patients older than 40 and with metformin use within the year prior to initiation. We defined two outcomes, incident nephrolithiasis, among patients without a prior history of nephrolithiasis, and recurrent nephrolithiasis, among patients with a history of nephrolithiasis. We followed up the patients for three years after SGLT2i or GLP1 RA initiation. Additionally, as a sensitivity analysis we followed a per protocol approach where patients were censored when discontinuing treatment or switching between the exposure and comparator. We used propensity score weighting (standardized mortality ratio weighting) to control for potential confounding factors and Cox proportional-hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CI).
Results: We included 34,526 patients initiating SGLT2i and 19,487 patients initiating GLP1 RA. Among patients taking SGLT2i and GLP1 RA, we identified 104 and 113 events of incident nephrolithiasis, respectively. We estimated a weighted HR for the exposed group to SGLT2i of 0.43 (95% CI 0.34, 0.54). When looking at recurrent nephrolithiasis, we identified 1079 new users of SGLT2i and 627 of GLP1 RA, and 106 and 124 events respectively. We estimated a weighted HR of 0.43 (95% CI 0.34, 0.54) for SGLT2i use. In the per protocol analysis, which included 34,526 SGLT2i and 19,487 GLP1 RA new users, there were 76 and 98 incident events respectively, with an estimated weighted HR of 0.35 (95% CI 0.27, 0.45).
Conclusions: Our study found a 57% reduced risk of nephrolithiasis in patients initiating SGLT2i, compared to GLP1 receptor agonists. These results are in line with a previous analysis from Denmark and highlight the potential for SGLT2i to reduce the burden of nephrolithiasis.
.jpg "Adrian Martinez de la Torre, PhD photo")
