Use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) or glucagon-like peptide-1 (GLP-1) agonists may reduce the risk for recurrent kidney stones, according to data presented at the American Urological Association’s 2023 Annual Meeting in Chicago, Illinois.
In a study of patients with type 2 diabetes and a history of kidney stones, those prescribed SGLT2i were less likely to form kidney stones than patients prescribed other drug classes, including dipeptidyl peptidase 4 inhibitors (DPP-4i), GLP-1 agonists, or any non-SGLT2i therapy.1
Ridwan I. Alam, MD, MPH, of Johns Hopkins University School of Medicine in Baltimore, Maryland, and colleagues propensity-score matched SGLT2i users to 2 other groups: users of a DPP-4i or GLP-1 agonist and users of any non-SGLT2i. Each group included 3572 patients.
Compared with the SGLT2i group, patients treated with a DPP-4i or GLP-1 agonist and those treated with any non-SGLT2i had an approximately 23% higher risk for kidney stones, Dr Alam reported in a poster presentation.
The 1-, 3-, and 5-year cumulative incidence of kidney stones was 24.0%, 33.8%, and 35.9%, respectively, for SGLT2i recipients, 28.8%, 41.0%, and 44.0% for patients treated with a DPP-4i or GLP-1 agonist, and 29.2%, 40.1%, and 44.2% for those treated with any non-SGLT2i.
“When managing diabetic patients with a history of stones, the use of SGLT2i presents an attractive option due to the significantly decreased risk of future stone events when compared to other antihyperglycemic medications,” Dr Alam’s team concluded in a study abstract.
In a separate study, investigators found that GLP-1 agonists may offer protection against formation of uric acid stones in patients with type 2 diabetes and a history of kidney stones.2 Jennifer Lu, MD, of Stony Brook University Hospital in New York, and colleagues retrospectively studied 510 patients who had a history of kidney stones and had 24-hour urine studies. Of these, 86 had type 2 diabetes. Although the patients with type 2 diabetes had a significantly higher rate of uric acid stones compared with those without diabetes (31.7% vs 12.1%), the rate did not differ significantly between GLP-1 agonist users and those without diabetes (18.2% vs 12.1%).
Further, compared with patients without diabetes, patients with type 2 diabetes had significantly higher uric acid supersaturation rates (1.45 vs 0.94 mmol/24 h) and urinary oxalate concentrations (41.7 vs 36.14 mg) and significantly lower urine pH (5.62 vs 6.14), Dr Lu reported. Patients on GLP-1 agonists had significantly higher urinary citrate concentrations (927.94 mg) compared with other patients with type 2 diabetes (544.59 mg) and the nondiabetic cohort (566.55 mg).
The investigators observed no significant differences with metformin, sulfonylurea, DPP-4i, SGLT2i, or insulin.
“The significant increase in urine citrate and reduction in [uric acid] stone formation suggests a lithoprotective effect of GLP-1 agonists independent of weight or diabetes control,” the investigators concluded in a study abstract. Clinicians should consider recommending GLP-1 agonists to stone-forming patients with type 2 diabetes, they noted.
- Alam R, Winoker J, Nimmagadda N, Matlaga B. Use of sodium-glucose cotransporter (SGLT2) inhibitors in diabetic stone formers is associated with a reduced risk of future stone events. Presented at: AUA 2023, Chicago, Illinois, April 28-May 1. Abstract MP10-04.
- Zhao K, Shkolnik B, Lu J, et al. Lithoprotective effect of GLP-1 agonists in diabetic stone formers. Presented at: AUA 2023, Chicago, Illinois, April 28-May 1. Abstract MP10-05.