Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2022 Jun 16;107(7):e3003-e3007.
doi: 10.1210/clinem/dgac154.

Empagliflozin and Decreased Risk of Nephrolithiasis: A Potential New Role for SGLT2 Inhibition?

Priyadarshini Balasubramanian  1 , Christoph Wanner  2 , João Pedro Ferreira  3   4 , Anne Pernille Ofstad  5 , Amelie Elsaesser  6 , Bernard Zinman  7 , Silvio E Inzucchi  1
Affiliations
Randomized Controlled Trial

Empagliflozin and Decreased Risk of Nephrolithiasis: A Potential New Role for SGLT2 Inhibition?

Priyadarshini Balasubramanian et al. J Clin Endocrinol Metab. .

Erratum in

Abstract

Context: Diabetes mellitus is a risk factor for nephrolithiasis. A recent observational study found that in patients with type 2 diabetes (T2D), SGLT2 inhibitor use was associated with a 49% lower risk of nephrolithiasis compared with GLP-1 receptor agonists.

Objective: We examined the association between nephrolithiasis and the SGLT2 inhibitor empagliflozin, using existing data from randomized clinical trials.

Methods: We pooled data from 15 081 T2D patients randomized to empagliflozin (n = 10 177) or placebo (n = 4904) from 20 phase I-IV trials, including the large cardiovascular outcome trial, EMPA-REG OUTCOME. Incident urinary tract stone events were captured using a predefined collection of MedRA terms. A sensitivity analysis using a narrower definition was also performed. Incidence rate ratios (IRR) and 95% CIs were calculated using the relative risk estimate, stratified by study.

Results: The median exposures to study drug were 543 days (placebo) and 549 days (empagliflozin); 183 patients experienced an incident urolithiasis during follow-up (placebo, 79; empagliflozin, 104), yielding annual incidence rates of 1.01 vs 0.63 events/100 patient-years in the 2 respective groups. The IRR was 0.64 (95% CI, 0.48-0.86), in favor of empagliflozin. In the sensitivity analysis, the results were similar (IRR, 0.62 [95% CI, 0.45-0.85]).

Conclusion: Compared with placebo, empagliflozin therapy was associated with an approximate 40% reduced risk of urinary tract stone events in T2D patients. The underlying mechanisms are unknown but may involve altered lithogenic profile of the urine. Dedicated randomized prospective clinical trials are warranted to confirm these initial observations in patients with and without T2D.

Keywords: SGLT2 inhibitors; empagliflozin; nephrolithiasis; type 2 diabetes mellitus.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Incidence rate ratios of empagliflozin vs placebo of urinary tract lithiasis in 15 081 patients with type 2 diabetes.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Khan SR, Pearle MS, Robertson WG, et al. . Kidney stones. Nat Rev Dis Primers. 2016;2:16008. - PMC - PubMed
    1. Geraghty RM, Cook P, Walker V, Somani BK. Evaluation of the economic burden of kidney stone disease in the UK: a retrospective cohort study with a mean follow-up of 19 years. BJU Int. 2020;125(4):586-594. - PubMed
    1. Antonelli JA, Maalouf NM, Pearle MS, Lotan Y. Use of the National Health and Nutrition Examination Survey to calculate the impact of obesity and diabetes on cost and prevalence of urolithiasis in 2030. Eur Urol. 2014;66(4):724-729. - PMC - PubMed
    1. Kristensen KB, Henriksen DP, Hallas J, Pottegard A, Lund LC. Sodium-glucose cotransporter 2 inhibitors and risk of nephrolithiasis. Diabetologia. 2021;64(7):1563- 1571. - PubMed
    1. Kinduryte Schorling O, Clark D, Zwiener I, Kaspers S, Lee J, Iliev H. Pooled Safety and Tolerability Analysis of Empagliflozin in Patients with Type 2 Diabetes Mellitus. Adv Ther. 2020;37(8) 3463-3484. - PMC - PubMed

Publication types

MeSH terms