Treatment with metformin and/or pioglitazone may have anti-inflammatory effects in patients with both multiple sclerosis (MS) and metabolic syndrome, study data indicate.
Laura Negrotto, MD, of the Institute for Neurological Research Dr Raúl Carrea in Buenos Aires, Argentina, and colleagues tested the effects of metformin and pioglitazone in 50 patients with MS who were also diagnosed with metabolic syndrome. Treatment effects were measured through MRI and serum leptin and adiponectin levels, as well as T-cell number and function.
Metabolic syndrome and the environmental factors that contribute to it have previously been linked to several autoimmune diseases. Identification of these factors is very important in order to address obstacles in the treatment and prevention of MS, wrote Aiden Haghikia, MD, and Ralf Gold, MD, in an accompanying editorial.
“…despite remarkable progress in the field of MS genetics, its usefulness for clinical diagnostics and therapy is unclear…” they wrote, regarding the small percent of genetic risk involved with developing MS. “…the increasing efforts to shed further light on potential environmental risk factors for MS results in the discovery of more causes of the disease, as well as the prospect to counteract these causes in a therapeutic sense.”
For the current study, 20 patients received metformin (850-1500 mg/d), 10 patients received pioglitazone (15-30 mg/d), and 20 untreated patients served as controls. The groups were similar in age, sex, BMI, disease duration, relapse rate, and treatment status, and were followed up for a mean 26.7 months.
After 6 months of treatment, patients treated with either drug therapy showed a significant decrease in the number of new or enlarging T2 lesions (metformin, 2.5 at baseline to 0.5 at 24 months; pioglitazone, 2.2 at baseline to 0.6 at 24 months). Gadolinium-enhancing lesions also decreased (metformin, 1.8 at baseline to 0.1 at 24 months; pioglitazone, 2.2 at baseline to 0.3 at 24 months). Compared to controls, patients treated with either therapy showed a decrease in mean leptin levels (metformin, 5.5 [2.4] vs 10.5 [3.4] ng/mL, P< .001; pioglitazone, 4.1 [0.8] vs 11.0 [2.6] ng/mL, P< .001) and increase in mean adiponectin serum levels (metformin, 15.4 [5.5] vs 4.5 [2.4] μg/mL, P< .001; pioglitazone, 12.6 [3.6] vs 4.8 [0.6] μg/mL, P< .001). In patients who received metformin, the mean number of myelin basic protein peptide-specific cells secreting interferon γ and interleukin-17 were significantly reduced compared to controls (interferon γ, 30.3 [11.5] vs 82.8 [18.8], P< .001; IL-17, 212.4 [85.5] vs 553.8 [125.9], P< .001). Those treated with pioglitazone also showed a significant decrease in the mean number of myelin basic protein peptide-specific cells secreting interleukin-6 and tumor necrosis factor compared to controls (IL-6, 361.6 [80.5] vs 1130.7 [149.21], P< .001; tumor necrosis factor, 189.9 [53.4] vs 341.0 [106.0], P< .001). Both treatment groups experienced a significant increase in the number and regulatory functions of CD4+CD25+FoxP3+ regulatory T cells compared with controls (metformin, 6.7 [1.5] vs 2.1 [1.0], P= .001; pioglitazone, 6.9 [0.8] vs 3.0 [0.8], P= .001).
Ultimately, both metformin and pioglitazone appear to have beneficial anti-inflammatory effects in MS, and should be explored further, study authors concluded.
- Negrotto L, Farez MF, Correale J. Immunologic Effects of Metformin and Pioglitazone Treatment on Metabolic Syndrome and Multiple Sclerosis. JAMA Neurol. 2016. doi:10.1001/jamaneurol.2015.4807.
- Haghikia A, Gold R. Positive Effect on Multiple Sclerosis With Treatment of Metabolic Syndrome. JAMA Neurol. 2016. doi:10.1001/jamaneurol.2015.5050.