Repurposing Drugs for Type 2 Diabetes
Look around. Think differently. What’s old may be new again.
Let’s call a spade a spade. Drug discovery is difficult. Joe Cornicelli’s blog that opened this series indicated as much and the facts do not lie either. When looking at small biotech groups all the way up to Big Pharma, (and factoring in the costs for all those drug failures) it costs a company between $800 million and $12 billion and between nine and 14 years to discover one new molecular entity to treat a disease, a recent analysis in Forbes suggests. The solution to this problem may be the word “new.” Old trends in the world are coming back in full force. Vinyl records—back. Hipsters and ironic moustaches, a new version of Kerouac’s beatnik hippie movement—back. It’s worth looking into the medicine cabinet as well for old therapeutics that may be rebranded for new treatments of type 2 diabetes (T2D).
The standards of care for T2D have been somewhat consistent for many years in various forms of drug combinations.Metformin, Sulfonylureas, Thiazolidinediones, DPP-IV inhibitors, and more recently GLP-1R agonists are all widely used and understood as agents that can control the progression of the diseases and enhance quality of life when used in combination with lifestyle interventions.1
However, groups that are vying for space in these target areas as a new best in class, or a fast follower of a widely prescribed agent may want to take pause. Going for another shot on goal with these specific drug discovery programs may yield a point on the scoreboard, but with an 8-2 lead in place—does that really make sense? Other groups may be targeting a niche pathway or enzyme that may not have a significant enough clinical outcome in this multifactorial disease. Whether groups are targeting the gut-brain axis, central regulation of appetite control, or increased energy expenditure they must take a step back and think about the integrated physiology that is T2D and imagine a new way to attack the same old disease, as the obvious targets have been hit long ago.
Outside the Box
Salsalate (a known non-steroidal anti-inflammatory drug) is a widely prescribed salicylate used for the treatment of pain and inflammation of various rheumatic conditions that goes back to the days of Hippocrates. A great credit goes to several investigators at Joslin Diabetes Center for carrying the torch of their namesake and looking to the past for how this drug might change the future of T2D. Elliot Joslin wrote the book on diabetes in the late 1800’s, and a group of researchers leading the clinical trial (TINSAL-T2D: Targeting Inflammation Using Salsalate for T2D) are also looking to the past—to a study from the late 1800s in particular—to repurpose salsalate for treatment of T2D. ). In clinical studies (found here, here, here and here)) that started about six years ago, this group has generated data showing that salsalate lowers HbA1c and improves other markers of glycemic control in T2D patients. While the long term cardiovascular and renal safety signals are yet to be finalized, this is a promising case of drug repurposing for T2D that did not take millions of dollars, years of medicinal chemistry, countless preclinical studies, and many gray hairs to bring a new therapeutic to market.
CRL Discovery Engine
Despite the fact that this conversation is centering on repurposing of known agents for T2D treatment the goal remains the same—bring a “new” item to market to treat this vast patient population. The Discovery Research Services (DRS) group at CRL has many arrows in its quiver that may help groups check off the boxes in the drug discovery process. With quick study initiation in rodent models of acute glucose handling,), a state of the art biomarker facility), and access to in-house consultants who are well versed in FDA regulations and strategy offered at no charge to clients, the DRS group can help the drug discovery process march down the pike.
In closing, the statistics on the spread of T2D across the globe are staggering and don’t need to be spelled out here. There are still opportunities for the scientific community to have an impact on this disease and, in turn, the quality of life for people that we know. Those opportunities may already be in clinical development, or at various stages of non-GLP science in your company. Look around. Think differently. What’s old may be new again.
- Diabetes Care, vol 37, supp 1, Jan 2013