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Pharmaceuticals

Hormone Mimics Make Progress On The Long Path To Becoming Obesity Or Diabetes Drugs

Small molecule improves indicators of diseases in mice; peptide moves into human clinical trials

by Carmen Drahl
November 4, 2013 | A version of this story appeared in Volume 91, Issue 44

Obesity and type 2 diabetes are still scourges, but effective treatments may come from mimicking hormones that regulate metabolism, two independent reports show. In one study, Richard D. DiMarchi of Indiana University, Bloomington, and colleagues made a hybrid peptide with elements from GLP-1 and GIP, two glucose-controlling hormones in the gut. This hybrid was more effective than currently approved medications at controlling blood glucose in animals, including monkeys. A study of the hybrid involving about 50 people with obesity and diabetes concluded that injections of it are safe: Few patients experienced the nausea commonly caused by this type of medication (Sci. Transl. Med. 2013, DOI: 10.1126/scitranslmed.3007218). Roche holds the license for the peptide. Meanwhile, in earlier-stage work, researchers in Japan mimicked adiponectin, a hormone secreted by fat cells that regulates glucose levels and fatty acid breakdown. The team, led by Takashi Kadowaki of the University of Tokyo, synthesized AdipoRon, a small molecule that activates two adiponectin receptors. AdipoRon had benefits similar to adiponectin in mice engineered to have diabetes (Nature 2013, DOI:10.1038/na​ture12656). It also prolonged life spans of diabetic mice on a high-fat diet. AdipoRon can be taken orally, unlike the hybrid peptide, but its half-life is only one hour.

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