Introduction: Type 2 Diabetes mellitus (T2DM) is associated with increased risk of calcium oxalate and uric acid (UA) stones. The most commonly prescribed medication for T2DM, Metformin, worsens this risk by increasing urinary oxalate, increasing urinary calcium and decreasing urine pH. With the increasing popularity of next-generation hypoglycemic agents, it is important to study the risk of stone formation with these newer medications. This study aims to assess the effects of various hypoglycemic agents on 24-hour urine studies in diabetic stone formers. Methods: A retrospective review was conducted for all patients with a history of nephrolithiasis and a 24-hour urine study seen between July 2017-December 2019 for an outpatient visit. Patients with T2DM were assessed for use of hypoglycemic agents (metformin, sulfonylurea, GLP-1 agonist, DPP-4 inhibitors, SGLT-2 inhibitors, insulin), stone analysis, BMI, HbA1c, and 24-hour urine study. Two-tailed t-tests were used for mean comparison and chi square tests for stone rate comparison. Results: Among the included 510 patients, 86 had T2DM (45 males, 41 females, mean age 63.6 years). Compared to the non-T2DM cohort, T2DM patients had lower urine pH (5.62 vs 6.14, p<0.00001), higher urine oxalate (41.7 vs 36.14, p=0.013) and higher UA supersaturation (1.45 vs 0.94, p<0.00001). Patients on GLP-1 agonists had greater urinary citrate than both the T2DM cohort (927.94 vs 544.59, p=0.007) and the non-T2DM cohort (566.55, p<0.0001). Between diabetic GLP-1 agonist users and non-users, there was no significant difference in BMI (non-GLP 33.1 vs GLP 35.4, p=0.34) or HbA1c (non-GLP 7.0 vs GLP 7.2, p=0.74). Though T2DM patients had higher rates of UA stones (31.7% vs 12.1%, p<0.0001), GLP-1 agonists users did not have a higher rate of UA stones compared to non-T2DM patients (18.2% vs 12.1%, p=0.54). There were no significant differences found with Metformin, sulfonylurea, DPP-4 inhibitors, SGLT-2 inhibitors, or insulin. Conclusions: T2DM is a known risk factor for nephrolithiasis, however, treatment with GLP-1 agonists may be litho-protective. The significant increase in urine citrate and reduction in UA stone formation suggests a lithoprotective effect of GLP-1 agonists independent of weight or diabetes control. Consideration should be made to recommend GLP-1 agonists to T2DM patients with nephrolithiasis. SOURCE OF Funding: None.
