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People with systemic lupus erythematosus (SLE) had lower rates of lupus nephritis, chronic kidney disease, and other complications when they were taking metformin, an analysis of medical records indicated.

Among some 88,000 SLE patients in an international records database, those not on metformin were 70% more likely to develop lupus nephritis (95% CI 17%-141%) and 27% more likely to have CKD (95% CI 7%-52%) during the first year after lupus diagnosis, relative to those using the drug, according to Yurilu A. Gonzalez Moret, MD, of Thomas Jefferson University in Philadelphia, and two colleagues.

Additionally, the propensity-matched analysis showed that major adverse cardiovascular events (MACE) were 21% more common in the no-metformin group (95% CI 0%-46%), the researchers .

Lupus nephritis and CKD rates remained significantly elevated in the absence of metformin treatment 5 years after SLE diagnosis (by 82% and 17%, respectively), Gonzalez Moret and colleagues found, but MACE rates were not.

"These findings underscore the potential protective effects of metformin in mitigating the progression of renal complications and cardiovascular events in individuals with SLE," the researchers 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."

It's just the latest study to show that metformin is not just a hypoglycemic agent for people with type 2 diabetes, although that is what it's primarily used for. Previous research has shown a plethora of other effects and clinical benefits: Gonzalez Moret and colleagues listed "antitumor, anti-aging, cardioprotective, anti-inflammatory, and immunomodulatory effects," plus an ability to "decrease immune cell activation and proliferation, proinflammatory cytokine production, and oxidative stress." The researchers also cited a showing that metformin reduced renal damage in a mouse model of SLE.

To see whether such an effect could be discerned in humans, Gonzalez Moret's group analyzed data from the TriNetX research collaboration, which collects records from 88 institutions in the U.S., Taiwan, Brazil, and Georgia, covering some 106 million patients. The researchers identified patients diagnosed with SLE with inpatient admissions from 2014 to early 2024: a total of 9,178 on metformin and 78,983 non-users.

Propensity matching was performed for demographics, lab parameters such as C-reactive protein and hemoglobin A1c, comorbidities, and medications taken at baseline. This yielded 7,242 metformin users matched to the same number of non-users.

After matching, patients had a mean age of 55-56; about 85% were women. Some two-thirds of both groups had diagnoses of type 2 diabetes and 8-9% were considered prediabetic. Two-thirds also had hypertension. Just over 40% had elevated blood lipids. About half of both groups were on corticosteroids and 40% were taking hydroxychloroquine. Statin use was common, but diabetes drugs other than metformin were not -- fewer than 10% were taking such agents as sulfonylurea, gliflozin, glucagon-like peptide-1 agonists, or dipeptidyl dipeptidase-4 inhibitors. However, some 40% of patients were insulin users.

Within 1 year after SLE diagnosis, the main outcomes -- lupus nephritis, stage 1-3 CKD, and MACE -- developed as follows:

• Lupus nephritis: 44 in users, 75 in non-users
• CKD: 212 in users, 258 in non-users
• MACE: 198 in users, 229 in non-users

And these were the outcome counts within 5 years:

• Lupus nephritis: 66 in users, 120 in non-users
• CKD: 518 in users, 577 in non-users
• MACE: 462 in users, 444 in non-users

In general, Gonzalez Moret and colleagues observed, these findings are in line with previous studies suggesting that metformin prevents or slows development of many conditions beyond type 2 diabetes. The study couldn't shed much light on the underlying mechanisms; however, the researchers indicated, suppression of pro-inflammatory immune processes is likely to be key.

Limitations to the study included its retrospective design and reliance on administrative records.

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