Oral antidiabetic medications have beneficial anti-inflammatory effects in patients with multiple sclerosis (MS) and metabolic syndrome, providing support for a link between metabolism and autoimmunity, researchers report.
They found that treatment with metformin or pioglitazone significantly decreased the number of new or enlarging T2 lesions or gadolinium-enhancing lesions after just 6 months, with benefits lasting for up to 2 years.
"This study is well in line with the recent growing interest in environmental risk factors associated with MS, in particular, those that are part of our daily habits such as diet", Aiden Haghikia and Ralf Gold, from Ruhr-University Bochum in Germany, comment in a related editorial.
For the open-label study, published in JAMA Neurology, 50 obese patients with MS who also developed metabolic syndrome underwent brain magnetic resonance imaging every 6 months following the initiation of metformin hydrochloride (850-1500 mg/day) in 20 patients and pioglitazone hydrochloride (15-30 mg/day) in 10 patients. The remaining 20 patients received neither treatment and served as controls.
After 2 years of treatment, the number of new or enlarging T2 lesions had decreased significantly from an average of 2.5 to 0.5 among patients taking metformin and from 2.3 to 0.6 among those given pioglitazone. Among controls, there was little change from the pre-treatment number of 2.4.
The drugs had a similar effect on gadolinium-enhancing lesions, the numbers of which decreased significantly after 2 years, from 1.8 before treatment to 0.1 with metformin and from 2.2 to 0.3 with pioglitazone.
This reduced inflammatory activity was accompanied by a significant suppression of levels of the proinflammatory adipokine leptin and a significant increase in the anti-inflammatory adipokine adiponectin with either treatment compared with none, note researcher Jorge Correale (Institute for Neurological Research Dr Raúl Carrea, Buenos Aires, Argentina) and colleagues.
The mediating factors were AMP-activated protein kinase (AMPK) induction in the peripheral blood mononuclear cells in the case of metformin and peroxisome proliferator-activated receptor (PPAR)γ induction in the case of pioglitazone.
Increased AMPK expression resulting from metformin treatment was associated with a significant decrease in the numbers of cells producing interferon γ and interleukin (IL)-17. Meanwhile, PPARγ induction with pioglitazone was associated with a significant decrease in the number of cells producing IL-6 and tumour necrosis factor.
With either drug, there was a robust increase in CD4+CD25+FoxP3+ regulatory T (Treg) cells, which in reduced numbers contribute to a chronic inflammatory state in obese individuals, the researchers note.
"Collectively, these observations provide both in vitro and in vivo evidence that metformin and pioglitazone treatment regulate immune and inflammatory responses and support recommendations of weight reduction in obese patients with MS", they conclude.
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