July 25, 2017
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Alzheimer’s disease drug may alleviate metabolic syndrome symptoms

Galantamine, an Alzheimer’s drug currently on the market, may be effective for reducing insulin resistance and inflammation in adults with metabolic syndrome, according to findings published in JCI Insights.

“It’s been very tough to come up with a treatment that targets all the components of metabolic syndrome, which is becoming a pandemic because it stems from obesity,” Valentin A. Pavlov, PhD, associate professor in the Center for Biomedical Science and Center for Bioelectronic Medicine at the Feinstein Institute for Medical Research, Northwell Health in Manhasset, New York, said in a press release. “By repurposing galantamine, it means we don’t have to start from zero to establish its safety. We already know a lot about its safety profile based on previous studies.”.”

Pavlov and colleagues evaluated 60 adults with metabolic syndrome randomly assigned to oral galantamine, an acetylcholinesterase inhibitor, 8 mg daily for 4 weeks followed by 16 mg daily for 8 weeks (mean age, 40.8 years; n = 30) or placebo (mean age, 42.7 years; n = 30) to determine the effects of the drug on markers of inflammation implicated in insulin resistance and cardiovascular risk and other metabolic and CV indices.

“Galantamine can target the entire syndrome as well as targeting components of the syndrome,” Yael Tobi Harris, MD, chief of endocrinology, diabetes and metabolism at North Shore University Hospital and Long Island Jewish Medical Center, said in the release. “Using an existing drug is a much faster way of getting a treatment out there. It’s promising, it makes me optimistic, and it’s a starting point indicating an avenue of research that should be pursued further.”

At the end of the 12-week treatment period, galantamine decreased plasma levels of tumor necrosis factor (P = .035) and increased plasma levels of IL-10 (P = .002) compared with placebo. No significant effects on IL-6 were observed with galantamine.

Compared with placebo, galantamine also decreased plasma levels of leptin (P < .0001) and the leptin to adiponectin ratio (P < .0001) and increased plasma levels of adiponectin (P < .0001).

Further, galantamine reduced homeostasis model assessment of insulin resistance (P = .008), insulin levels (P = .01) and the low-frequency power of heart rate variability (P = .005) compared with placebo.

Further, galantamine reduced homeostasis model assessment of insulin resistance (P = .008), insulin levels (P = .01), glucose levels (P = .077) and the low-frequency power of heart rate variability (P = .005) compared with placebo.

Nonsignificant increases were observed for HDL cholesterol and LDL cholesterol, and nonsignificant decreases were observed for triglyceride and total cholesterol levels with galantamine compared with placebo.

No significant differences were observed between the two groups for systolic blood pressure, diastolic BP, awake systolic BP, awake diastolic BP, sleep systolic BP or sleep diastolic BP.

“Our results demonstrate that galantamine, a drug in clinical use for the symptomatic treatment of Alzheimer’s disease, ameliorates important components of [metabolic syndrome] pathogenesis, including inflammation and insulin resistance, and alters autonomic tone,” the researchers wrote. “These effects were seen at a low galantamine dose, and the drug was extremely well tolerated. Further studies to examine the predictive value of these favorable alterations in inflammation and insulin resistance in this at-risk population and the long-term clinical benefits of galantamine in the treatment of [metabolic syndrome] should be pursued.” – by Amber Cox

Disclosures: Pavlov reports having published patents broadly relevant to the work and has assigned their rights to the Feinstein Institute for Medical Research. Harris reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.