How Does R&D Deal With the Explosion in the Incidence of Diabetes?

A recent story in Lancet, a British medical journal, showed that since 1980 the incidence of type 2 diabetes has doubled globally to 347 million and tripled in the United States, where the Center for Disease Control (CDC) estimates that 1 in 12 Americans have this disease.  Instead of triggering alarms among those focused on health care issues, this scientific paper seems to have received only modest attention.  Gautam Naik did cover it in the Wall Street Journal and his quote from one of the study’s authors, Professor Majid Ezzati, was on the mark: “Diabetes is a long-lasting and disabling condition, and it’s going to be the largest cost for many health care systems.”

It is not as if this epidemic has a mysterious cause.  The growth in the incidence of type 2 diabetes is directly related to obesity. The CDC has been following the girth of America for the past two decades and the results are startling (www.cdc.gov).  There are now nine states in this country where one-third of the population has a body mass index of over 30, or, in other words, is categorized as obese (to put this in perspective, a 5’9’’ man who weighs 210 pounds has a BMI of 30).  As people get heavier, the cells in their body are less able to utilize insulin.  This inability leads to increased levels of sugar in the blood stream, which, if left untreated, can result in vascular complications leading to heart disease, kidney failure and blindness.

The obvious solution to this problem is getting people to exercise more, eat less and embrace a healthier lifestyle.  While admirable efforts to achieve these goals are being made on multiple fronts, they aren’t working.  Thus, people are going to need to have the option of drug therapy to help alleviate the symptoms and ward off the deleterious downstream effects of diabetes.  But this solution isn’t so straightforward.  While there are drugs currently available to treat diabetes, their effects are modest.  Furthermore, two anti-diabetic drugs, Avandia and Actos, have been found to be deficient in terms of their risk-benefit profile; as a result, Avandia is no longer prescribed and Actos’ use is highly limited.

Equally as concerning is the fact that the R&D pipeline of potential new anti-diabetic drugs is not impressive.  While great drugs have been found to treat high blood pressure and to lower cholesterol, diabetes drug discovery has proven to be much more difficult.  New drugs for diabetes must be viewed as a major priority for all involved in the discovery and development of new medicines.  As such, R&D in this area needs to be given a much higher priority, particularly by governmental agencies.  Here are a few suggestions:

1)      More needs to be invested in basic research – The NIH sets the national health priorities by where it invest its budget.  Of its $32 billion projected research budget for 2012, the NIH only allotted $1.06 billion to diabetes research.  In contrast, the cancer budget (across all of the various cancers such as lung, breast, etc.) comes to $8.15 billion.  The investment  in cancer research by the NIH over the past three decades has helped to produce a spectacular pipeline of almost 1,000 new anti-cancer agents currently in development, certainly indicative of the priority this area of research has received.  But even the infectious diseases budget is 4 times that of diabetes.  Given the enormous prevalence of diabetes, perhaps some redistribution of NIH funds is in order so that more research into understanding diabetes disease mechanisms can be generated.

2)      The FDA needs to be more creative in clinical trial paradigms – the FDA has been under siege recently because of its approval, then subsequent withdrawal of diabetes drugs.  As a result of the Avandia and Actos incidents, any new drug to treat diabetes is now required to complete an outcome study  (in which patients are studied while on drug for three years and events such as heart attacks, strokes, etc. are measured)  before it is reviewed by the FDA.  Studies like these cost hundreds of millions of dollars and, although patients are on the drug for three years, these studies take five years to complete given their complexity.  In order to discover a truly novel breakthrough drug for diabetes, the FDA needs to be flexible in its approval requirements.  Given the epidemic nature of diabetes, the FDA needs to address the disease with the same urgency it attacks AIDS and cancer.  It should use its approach to AIDS and cancer trials as a blueprint for its treatment of diabetes, perhaps even reducing the initial outcome study to a year instead of three years.  If this study is successful, the drug can be approved by the FDA with the proviso that a three year study will begin immediately on approval.3)      Pharmaceutical companies need to rededicate themselves to this area of research – there is no doubt that R&D in this area is risky.  Novel mechanisms are speculative to work on and the clinical trials are difficult, particularly if you are trying to measure the impact of an experimental drug on diabetic complications like kidney disease or retina degradation.  Furthermore, there is risk involved when it is unclear how difficult the regulatory pathway is going to be.  But big pharma needs to rise to the challenge here as they are the ones whose experimental drug will prove or disprove much of the early hypothetical work coming from academia and the NIH.

The cost to society from the diabetes epidemic is going to be huge.  Changes in how we approach the discovery of new anti-diabetics have to occur now in order to have an impact in the next decade.