Because glucagon raises blood glucose in the liver, it's counter-intuitive to think of it as the basis for a strategy to treat obesity and its associated consequences, including adult onset diabetes. But a research team has shown that a single-molecule "co-agonist" of glucagon and GLP-1 normalizes glucose tolerance and reduces body fat and weight in preclinical models. This molecular-level polypharmacy is particularly appealing in metabolic disease, where single mechanisms tend to offer only modest therapeutic effects.

Researchers have identified a protein in the mitochondria -- where cells generate the energy needed to drive biological processes -- that is dramatically upregulated by nutrient restriction. It appears to protect the cell from stress, in keeping with observations that caloric restriction diets slow aging. The researchers go on to show that a set of other proteins activated in turn by this process may be targets for the development of therapies for neurodegenerative diseases and diabetes.

The unanimous rejection of Sanofi-Aventis' obesity drug rimonabant by an FDA Advisory Committee in June hasn't put off the host of firms, large and small, seeking an answer to the obesity epidemic. Despite the many drug casualties in this area, still, it seems, no approach is ruled out.