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The Double-edged Sword of Diabetes Drug Development

This article was originally published in Start Up

Executive Summary

Intense interest in new diabetes drugs gives start-ups many choices for technology development or in-licensing, but recent regulatory caution also increases risk.

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Marrying Glucagon with GLP-1 to Treat Obesity

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.

Omentec Biosciences Inc.

Omentec was formed around omentin, a protein selectively expressed in visceral (central) adipose tissue, where fat is stored. Visceral obesity, as opposed to subcutaneous (peripheral) fat accumulation, is associated with a higher risk of diabetes and cardiovascular disease. That omentin is found mostly in visceral adipose tissue suggests it may be an important signaling factor in fat metabolism, insulin sensitivity, and inflammation, with therapeutic and diagnostic applications.

Januvia: Defining Primary-Care Success and Risk

Januvia's fast development and successful launch exemplifies Merck's new biomarker-based R&D operation and its focused "one Merck" strategy. But the drug also provides an ideal case study of why doing everything right in primary care brings with it extraordinary risks: the key elements of Januvia's success -- blazing speed through development and the extraordinary safety profile on which its commercial triumph depends -- also define its most dangerous commercial liabilities.

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