Sodium-glucose cotransporter 2 inhibitor use in patients with type 2 diabetes linked to decreased risk of nephrolithiasis

1. A reduced risk of nephrolithiasis was linked with patients with type 2 diabetes (T2D) initiating sodium-glucose cotransporter 2 inhibitor (SGLT2i) treatment compared to starting glucagon-like peptide 1 receptor agonists (GLP-1RA) or dipeptidyl peptidase 4 inhibitors (DPP4i).

2. The results of the study remained consistent across various predetermined sensitivity analyses and subgroup evaluations (some being race, sex, and lifestyle factors).

Evidence Rating Level: 2 (Good)

Study Rundown: Kidney stone prevalence is increasing globally, posing significant costs and health risks. T2D is associated with a higher risk of kidney stones, and SGLT2is may reduce this risk by altering urine composition. Recent analyses suggest a decreased risk of nephrolithiasis with certain SGLT2is, despite earlier studies showing no significant association. This study fills a gap by examining the association between SGLT2i use and nephrolithiasis risk in a large US population of patients with T2D receiving routine clinical care. This study found that there was a decreased risk of kidney stones with those initiating SGLT2i treatment in comparison to other glucose-lowering agents like GLP-1RA and DPP4i. One limitation of this study was the use of diagnostic codes for classifying nephrolithiasis which may result in incorrectly under- or overreporting. In conclusion, this analysis may inform providers of which glucose-lowering agent to choose for patients diagnosed with T2D who may have an increased risk of nephrolithiasis.

Click to read the study in JAMA Internal Medicine

Relevant Reading: Association of SGLT2 Inhibitors With Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes: A Meta-analysis

In-Depth [retrospective cohort]: This study is a population-based, new-user, active comparator cohort study using data from 3 nationwide US databases. This study’s analysis was completed between July 2021 to June 2023 using data from April 2013 to December 2020. The study population included commercially insured patients with T2D over or equal to the age of 18 who started an SGLT1i, DPP4i, or GLP-1RA. Exclusion criteria included patients with any recorded history of nephrolithiasis or urolithiasis. The primary outcome of this study was the claim code used in a patient encounter diagnosing nephrolithiasis. During a median follow-up period of 192 days (interquartile range (IQR), 88-409), patients initiating an SGLT2i exhibited a lower risk of nephrolithiasis compared to those starting a GLP-1RA (14.9 vs 21.3 events per 1000 person-years; hazard ratio (HR), 0.69 [95% CI, 0.67-0.72]; rate difference (RD), −6.4 [95% CI, −7.1 to −5.7]) or a DPP4 inhibitor (14.6 vs 19.9 events per 1000 person-years; HR, 0.74 [95% CI, 0.71-0.77]; RD, −5.3 [95% CI, −6.0 to −4.6]). The results of the study remained consistent across various predetermined sensitivity analyses and subgroup evaluations (sex, race/ethnicity, chronic kidney disease, and obesity).

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