SGLT2 Inhibitors Reduce Nephrolithiasis Risk

Researchers at Mass General Brigham found that among patients with type 2 diabetes, those who started taking SGLT2 inhibitors had lower rates of kidney stones compared to patients who started taking other classes of diabetes medications.

Kidney stone rates are increasing in the United States and around the world. Type 2 diabetes is associated with an increased risk of kidney stones, but some forms of treatment for this condition may also have the benefit of reducing the risk of kidney stones. In a study led by researchers at Mass General Brigham, researchers found that there was an association between the use of sodium-glucose countertransporter 2 (SGLT2) inhibitors and a lower risk of developing kidney stones. Their findings are published in JAMA Internal Medicine .

Researchers from Brigham and Women’s Hospital and Massachusetts General Hospital, founding members of the Mass General Brigham health care system, worked together to conduct the analysis. "Our findings could help inform clinical decision-making for patients with diabetes who are at risk of developing kidney stones," said corresponding author Julie Paik, MD, ScD, MPH, of the Division of Pharmacoepidemiology and Pharmacoeconomics and the Division of Renal (Kidney). Medicine at Brigham and Women’s Hospital. 

Importance  

Type 2 diabetes (T2D) is associated with an increased risk of kidney stones. Sodium-glucose cotransporter 2 (SGLT2is) inhibitors may reduce the risk of nephrolithiasis by altering urine composition. However, no studies have investigated the association between SGLT2i use and the risk of nephrolithiasis in patients receiving usual care in the US.

Aim  

To investigate the association between the use of SGLT2i and the risk of nephrolithiasis in clinical practice.

Design, environment and participants  

This new-user active comparator cohort study used data from commercially insured adults (age ≥18 years) with type 2 diabetes who initiated treatment with SGLT2is, glucagon-like peptide-1 receptor agonists (GLP-1RA), or dipeptidyl. peptidase 4 inhibitors (DPP4is) between April 1, 2013 and December 31, 2020. Data were analyzed from July 2021 to June 2023.

Exposure  

New initiation of an SGLT2i, GLP-1RA or DPP4i.

Main results and measures  

The primary outcome was nephrolithiasis diagnosed using International Classification of Diseases codes in the inpatient or outpatient setting.

New users of SGLT2i were matched on a 1:1 propensity score basis with new users of GLP-1RA or DPP4i in pairwise comparisons. Incidence rates, rate differences (RD), and estimated hazard ratios (HR) with 95% CIs were calculated.

Results  

After 1:1 propensity score matching, a total of 716,406 adults with type 2 diabetes (358,203 pairs) initiated an SGLT2i or a GLP-1RA (mean [SD] age, 61.4 [9.7] years for both groups; 51.4% vs. 51.2% women; 48.6% vs. 48.5% men) and 662,056 adults (331,028 pairs) who started an SGLT2i or a DPP4i (mean [SD] age, 61. 8 [9.3] versus 61.7 [10.1] years; 47.4% versus 47.3% women; 52.6% versus 52.7% men were included).

During a median follow-up of 192 (IQR, 88-409) days, the risk of nephrolithiasis was lower in patients who initiated an SGLT2i than among those who initiated a GLP-1RA (14.9 vs. 21.3 events per 1,000 person-years; HR, 0.69 [95% CI, 0.67-0.72]; RD, −6.4 [95% CI, −7.1 to −5.7]) or a DPP4i (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 association between SGLT2i use and nephrolithiasis risk was similar by sex, race and ethnicity, history of chronic kidney disease, and obesity.

The magnitude of risk reduction with SGLT2i use was greater among adults younger than 70 years versus those 70 years or older (HR, 0.85 [95% CI, 0.79-0.91]; RD, −3.46 [95% CI, −4.87 to −2.05] per 1000 person-years; P for interaction <0.001).

Reference : Paik JM et al. “Sodium-Glucose Cotransporter 2 Inhibitors and Nephrolithiasis Risk in Patients With Type 2 Diabetes” JAMA Internal Medicine DOI: 10.1001/jamainternmed.2023.7660