Metabolic approach could have potential in reducing lupus flares

The diabetes drug metformin could hold potential as a treatment for reducing the incidence of flares in people with lupus, a small study suggests.

The trial from Shanghai included patients with mild disease on standard immunosuppressive treatment who were randomised to receive metformin (n=67; 0.5g up to three times a day) or placebo (n=73).

At 12 month follow-up no significant difference was seen in the primary endpoint of incidence of lupus flares between treatment groups (n=14 in the metformin group versus 25 in the placebo group; relative risk 0·68, 0·42–1·04, p=0·078).

However, an exploratory analysis suggested metformin reduced the frequency of major flares (defined according to SELENA-SLEDAI) compared to placebo (n=9 vs n=20; RR 0.59, p=0.042).

The frequency of serious adverse events was similar between the two patient groups.

“Our trials suggest that metformin has a favourable safety profile in patients with SLE. Considering this finding and its extremely low cost, larger and longer trials in different ethnic populations might be considered to investigate its potential effect on reducing the frequency of flares, particularly major flares, for patients with SLE with low-grade disease activity but at risk of relapse,” the research team concluded in their paper published in Lancet Rheumatology.

Writing in an accompanying editorial, lupus expert Dr Mandana Nikpour from St Vincent’s Hospital in Melbourne said that while it was tempting to interpret a 40% reduction in major flares as a positive treatment response, the exploratory nature of the  analysis, albeit with multiplicity adjustment for significance, warranted “guarded interpretation”.

She said the lack of a steroid sparing effect seen in the trial was also disappointing given the morbidity associated with steroid treatment suggested that dose reduction should be “an essential element of assessing the clinical utility of emergent therapies.”

“Although the pursuit of further clinical trials of adjunct therapy with metformin for SLE is likely to be challenging , the burgeoning concept of manipulating metabolic pathways in immune cells might prove fruitful in SLE drug development,” she added.

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