medwireNews: Sodium-glucose cotransporter (SGLT)2 inhibitors reduce the risk for developing kidney stones more than two other commonly used treatments for type 2 diabetes, suggest the results of a large US population-based cohort study.
Newly starting treatment with an SGLT2 inhibitor was associated with a 31% reduction in the risk for nephrolithiasis compared with new use of a glucagon-like peptide (GLP)-1 receptor agonist, and a 36% reduction when compared with new use of dipeptidyl peptidase (DPP)-4 inhibitor over a median follow up of approximately 6 months.
“Our study may help to inform decision-making when considering the prescribing of glucose-lowering agents to patients with [type 2 diabetes] who may be at risk for developing nephrolithiasis,” Julie Paik (Brigham and Women’s Hospital, Boston, Massachusetts, USA) and co-authors write in JAMA Internal Medicine.
It has been suggested that SGLT2 inhibitors might lower the risk for nephrolithiasis by altering urine composition. This is plausible for several reasons, say the researchers, one of which is that SGLT2 inhibitors increase urinary citrate excretion which plays a role in stopping kidney stone formation.
Prior data on the association are conflicting, however, with a meta-analysis of randomized trials finding no association between SGLT2 inhibitor use and risk for nephrolithiasis, but pooled data from empagliflozin trials and a separate Danish registry trial both indicating a significant reduction in the risk.
The present study examined the possible association in a routine clinical practice situation. Data from three medical insurance claim databases were used to perform an active comparator, new-user study. Adults with type 2 diabetes were eligible for inclusion if they were aged 18 years or older, had just started treatment with an SGLT2 inhibitor, GLP-1 receptor agonist, or DPP4-inhibitor, and had no prior history of kidney or urinary tract stones.
New initiation of treatment was defined as having a filled prescription for the drug in question, without having had a prescription dispensed in the previous year.
A total of 1,378,462 commercially insured adults with type 2 diabetes were included in the study: 716,406 formed the cohort used to compare SGLT2 inhibitors with GLP-1 receptor agonists, and 662,056 were used to compare SGLT2 inhibitors with DPP-4 inhibitors.
Propensity score matching was used to ensure that the cohorts were similar in terms of their baseline characteristics. The mean age of participants was around 61 years overall, approximately half of each cohort were men, and around 70% were White.
In the SGLT2 inhibitor versus GLP-1 receptor agonist cohort, a respective 4670 and 6134 cases of nephrolithiasis were identified. This gave respective incidence rates per 1000 person–years of 14.9 versus 21.3 events and a hazard ratio (HR) of 0.69 favoring SGLT2 inhibitor use.
And in the SGLT2 inhibitor versus DPP-4 inhibitor cohort, a respective 4438 and 5769 nephrolithiasis cases were identified, giving incidence rates of 14.6 versus 19.9 events per 1000 person–years and a HR of 0.74.
In both cohorts, the cumulative incidence curves of nephrolithiasis over time started to separate after approximately 1 month.
“Findings were consistent when we performed an analysis similar to an intention-to-treat approach,” note the researchers.
Factors such as sex, race and ethnicity, history of chronic kidney disease, or obesity did not seem to affect the results.
Patient age, however, did seem to have an effect, with patients aged younger than 70 years being more likely than those aged 70 years or older to experience a greater reduction in risk with SGLT2 inhibitor versus either of the other treatments.
“We speculate that this finding could be related to the change in stone composition that occurs with aging,” say Paik and colleagues.
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