Patients With Type 2 Diabetes Using SGLT2is for Treatment at Low Risk of Nephrolithiasis

Patients with type 2 diabetes (T2D) who have initiated treatment with sodium-glucose cotransporter 2 inhibitors (SGLT2is) may be at a lower risk of nephrolithiasis when compared with patients using glucagon-like peptide 1 receptor agonists (GLP-1RAs) or dipeptidyl peptidase 4 inhibitors (DPP4is).

Researchers sought to investigate the association between the use of SGLT2i in patients with T2D and nephrolithiasis risk. Included in the study were adults aged 18 years and older with T2D who initiated treatment on either SGLT2is, GLP-1RAs, or DPP4is between April 2013 and December 2020.

In the new-user, active comparator cohort study conducted by researchers, new SGLT2i users were 1:1 propensity score matched to new users of GLP-1RA (n = 716,406 [358,203 pairs]) or DPP4i (n = 662,056 [331,028 pairs]).

After a 192-day follow up, the risk of nephrolithiasis in patients was lower in those who initiated SGLT2i than among those who were using GLP-1RA (14.9 vs 21.3 events; [hazard raito] HR, 0.69 [95% CI, 0.67-0.72]; [rate differences] RD, −6.4 [95% CI, −7.1 to −5.7]) or DPP4i (14.6 vs 19.9 events; HR, 0.74 [95% CI, 0.71-0.77]; RD, −5.3 [95% CI, −6.0 to −4.6]). Further, the association between patients who used SGLT2i and nephrolithiasis risk was similar by sex, race and ethnicity, history of chronic kidney disease, and obesity. Nephrolithiasis risk reduction with SGLT2i use was larger among adults aged younger than 70 years vs aged 70 years or older.
The study had some limitations. The researchers noted that they could not rule out potential residual confounding. They attempted to address this limitation by adjusting for a large number of clinically relevant confounders and confounder proxies. Additionally, nephrolithiasis was diagnosed in patients using diagnosis codes, so there was potential for misclassification.
Despite the few limitations, the research may help clinicians manage their patients with T2D.

“In this large US cohort study of patients with T2D, initiation of SGLT2is compared with initiation of either GLP-1RAs or DPP4is was associated with a lower risk of nephrolithiasis,” the researchers concluded. “Our study may help to inform decision-making when considering the prescribing of glucose-lowering agents to patients with T2D who may be at risk for developing nephrolithiasis.”

Reference:
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;184(3)z:265-274. doi:10.1001/jamainternmed.2023.7660