SGLT2 inhibitors and nephrolithiasis risk: a meta-analysis

Area of Science:

• Nephrology
• Endocrinology
• Pharmacology

Background:

• Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a class of anti-diabetic medications.
• These drugs demonstrate beneficial effects on cardiovascular and renal outcomes, metabolic parameters, and body weight.
• Emerging research explores their impact on nephrolithiasis (kidney stone) development, a condition affecting 10% of the population and posing risks for kidney injury.

Purpose of the Study:

• To systematically review and meta-analyze the association between SGLT2 inhibitor therapy and the risk of nephrolithiasis.
• To compare the incidence of kidney stones in patients treated with SGLT2 inhibitors versus control groups (placebo or active therapies).

Main Methods:

• A comprehensive literature search was conducted across multiple databases (PubMed, Ovid MEDLINE, Web of Science, Scopus, Cochrane Library).
• Systematic review and meta-analysis guidelines (PRISMA) were followed.
• Data from six clinical trials, encompassing 11,635,698 patients with nephrolithiasis, were included in the analysis.

Main Results:

• Nephrolithiasis occurred in 1.27% of patients in the SGLT2 inhibitor group versus 1.56% in the control arm.
• SGLT2 inhibitor therapy was associated with a significantly lower risk of nephrolithiasis compared to placebo (OR 0.61, P < .00001).
• A reduced risk was also observed compared to active therapies like GLP-1 and DPP-4 inhibitors (OR 0.66, P = .02).

Conclusions:

• SGLT2 inhibitor therapy is associated with a reduced risk of nephrolithiasis.
• Potential mechanisms include osmotic diuresis, reduced lithogenic substance concentration, anti-inflammatory/anti-fibrotic effects, and increased urine pH.
• Further large-scale randomized clinical trials are warranted to confirm these findings and elucidate mechanisms.