Reference: JAMA Intern Med. 2024 Jan 29:e237660
Practice Point: SGLT2s may lower the risk of developing a first kidney stone by about 6 events per 1,000 person-years compared to GLP-1s and DPP4s, but this information is unlikely to affect diabetes medication selection.
EBM Pearl: Data farming is combing through huge datasets to find something to publish. Sometimes the results add to the body of evidence; sometimes they mean nothing.
Nephrolithiasis isn't top-of-mind among the complications associated with diabetes, particularly compared with heart disease, blindness, or kidney failure. Currently, GLP-1’s are winning the popularity race among treatment options. SGLT2s are known for their cardiac benefits, but a group of investigators recently reported that SGLT2s might protect against developing new kidney stones. They conclude that providers should consider that information when choosing among antidiabetic medications. This study does not appear to have been funded by pharma, but it’s pretty clear it was influenced by farming (of data).
The study was a retrospective database review of over 1 million commercially-insured adults in the US with type 2 diabetes who initiated treatment with SGLT2s, GLP-1s, or DPP4s from 2013-2020, looking for outpatient or inpatient ICD-10 codes for nephrolithiasis. Patients with prior nephrolithiasis were excluded. (Read that again.) Propensity score matching was used to try to offset any bias related to which participants might have been prescribed one drug over another. After that, 1:1 propensity score–matched cohorts were created and assessed for adequate balance between groups. (Translation: multiple appropriate steps were taken to ensure data were as trustworthy as possible.)
Analyses demonstrated significantly lower rates of nephrolithiasis with SGLT2s than GLP-1s or DPP4s by 6.4 and 5.3 events per 1,000 person-years, respectively. The magnitude of reduction was more pronounced in people younger than 70.
Ok great. SGLT2s lower the already low risk for new-onset kidney stones in adults with type 2 diabetes. Sorry (not sorry) to exhibit some cynicism here, but so what? Even though the authors’ main conclusion is that these findings should influence prescribing based on an assessment of risk factors for nephrolithiasis, we’re pretty sure that’s not going to be the reason they do or do not get prescribed. The authors of this article seem to be digging deep for any decent clinical outcomes from this dataset. But, following along with their conclusion that these results “could help to inform decision-making when prescribing glucose-lowering agents for patients who may be at risk for developing nephrolithiasis,” wouldn’t it make sense that the population studied would be those with prior stones, not the very small group of middle-aged people who develop their first stone ever? It seems to us that the slightly reduced risk of new-onset kidney stones might be a barely mentionable benefit of SGLT2s, but it sure isn’t going to change management. Both the baseline risk and absolute risk reduction are so small that the impact is clinically insignificant. More meaningful factors such as cardiac risk, weight loss, and regression of NAFLD (based on a new study published February 12 in JAMA that we’re going to write about next week!) are what should really drive medication selection for diabetes. But hey- we learned a couple things: 1) that the risk of nephrolithiasis is slightly higher with diabetes, and 2) that SGLT2s can slightly lower that risk.
For more information, see the topic Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors for Diabetes Mellitus in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Katharine DeGeorge, MD, MS, Senior Deputy Editor at DynaMed and Associate Professor of Family Medicine at the University of Virginia. Edited by Alan Ehrlich, MD, FAAFP, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School; Dan Randall, MD, MPH, FACP, Deputy Editor at DynaMed; Nicole Jensen, MD, Family Physician at WholeHealth Medical; Vincent Lemaitre, PhD, Medical Editor at DynaMed; Hannah Ekeh, MA, Senior Associate Editor at DynaMed; and Jennifer Wallace, BA, Associate Editor at DynaMed.