Renal, cardiovascular risks lower in patients with lupus using metformin
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Key takeaways:
- The risks for lupus nephritis, chronic kidney disease and MACE in patients with SLE were lower among those receiving metformin.
- Patients taking metformin had higher levels of HbA1C.
Metformin may protect against the progression of adverse renal and cardiovascular outcomes in patients systemic lupus erythematosus, including lupus nephritis and infarction, according to data published in ACR Open Rheumatology.
“Despite current evidence demonstrating the cardioprotective properties of metformin and intensive research linking SLE to [cardiovascular] risk, especially [lupus nephritis] and chronic kidney disease, the role of endothelial dysfunction and the underlying mechanisms remain incompletely understood without a specific targeted pharmacological treatment,” Yurilu A. Gonzalez Moret, MD, of Jefferson Einstein Hospital, in Philadelphia, and colleagues wrote. “Updated data regarding these complex mechanisms and new treatments targeting autoimmune-driven inflammatory responses are urgently needed.”
To investigate how metformin may impact renal and cardiovascular outcomes in patients with SLE, Gonzalez Moret and colleagues conducted a retrospective study using data from 88 health care organizations obtained through the TriNetX research network. The researchers analyzed data from 9,178 adults with SLE who used metformin, as well as 78,983 patients who had not used metformin, admitted to inpatient settings between January 2014 and April 21, 2024.
Using propensity score matching, the researchers compared each groups’ risks for developing biopsy-proven lupus nephritis; chronic kidney disease stage 1, 2 or 3; and major adverse cardiovascular events, including acute myocardial infarction and stroke. Comparisons were adjusted for demographic variables, laboratory results, associated comorbidities and medication use.
According to the researchers, propensity score matching showed that patients taking metformin demonstrated higher levels of HbA1C (6.8 ± 1.8 vs. 6.4 ± 1.8; P < .001), while those not taking metformin had elevated urea nitrogen (16.4 ± 9.7 mg/dL vs. 15.3 ± 7.6 mg/dL; P < .001).
One year from SLE diagnosis, patients not taking metformin demonstrated significantly higher risks for developing lupus nephritis (RR = 1.7; 95% CI, 1.17-2.41), chronic kidney disease (RR = 1.27; 95% CI, 1.07-1.52) and major adverse cardiovascular events (RR = 1.21; 95% CI, 1-1.46).
At 5 years, the risk remained elevated for lupus nephritis (RR = 1.82; 95% CI, 1.35-2.45) and chronic kidney disease (RR = 1.17; 95% CI, 1.04-1.31) among non-users, while the between-group difference for major adverse cardiovascular event risk was no longer statistically significant.
“These findings underscore the potential protective effects of metformin in mitigating the progression of renal complications and cardiovascular events in individuals with SLE,” Gonzalez Moret and colleagues wrote. “Further studies and clinical trials may be warranted to validate these findings and explore the underlying mechanisms responsible for the observed protective effects of metformin in patients with SLE.”
Perspective
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This is an interesting study using metformin, an oral anti-hyperglycemic drug, as a possible adjunct treatment for lupus nephritis prevention. It also suggests that slowing the development of chronic kidney disease (CKD) and major cardiovascular events (MACE) is possible. Clinically, patients with lupus nephritis have been our most difficult to manage and often progress to end-stage renal disease despite receiving proper treatment.
Ever since Urowitz and colleagues demonstrated the bimodal distribution of mortality in patients with systemic lupus erythematosus, an option to help prevent MACE outcomes later in SLE diagnosis has remained very attractive. Furthermore, the low price point of metformin would make this treatment widely acceptable to patients and providers.
This study is subject to the imperfections of retrospective database analysis. However, it also has strengths, including the sheer number of patients and the diversity of the patient population. Further study will be needed to verify these results. Questions of patient selection and metformin dosing would need to be answered, along with identifying the mechanism of action, since it seems to be independent of prednisone use in this study.
Although we are not yet ready to start every patient with SLE on metformin, this study certainly makes us hope we can repurpose this medication for better SLE outcomes.
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