November 14th marked the Annual World Diabetes Day in honoring the birthday of Frederick Banting, who teamed with Charles Best in the discovery of insulin in 1922. The discovery of insulin was truly an innovation.
John Lechleiter, CEO of Eli Lilly, a company that first sold insulin, wrote on the Paradox of Diabetes Research, “Before insulin, a diabetes diagnosis was often a death sentence; today, our company regularly recognizes people who have lived for 75 years and more with Type 1 diabetes. And yet, amid a growing worldwide epidemic of Type 2 diabetes and obesity, new breakthroughs are needed as urgently today as they were 90 years ago.”
I couldn’t agree with him more and would like to add my comments. There have been many companies who have worked on drugs for both Type 1 and Type 2 diabetes and most of the trials either did not meet primary end point, prove superior to what’s already on the market, or had safety issues.
Diabetes, like personalized medicine, is different for each individual and according to Lechleiter “Research in diabetes is moving towards targeted interventions for patients in different stages of the disease and for its various complications. And improved delivery systems – such as better injection devices or less frequent injections – can make it easier for people with diabetes to comply with their doctor’s orders.”
For Type 1 diabetes, the move toward a personalized closed loop system is where the trend is moving or devices that move away for daily injections. For Type 2 diabetes, BMS and AZ have developed the promise of a new class of drug, Forxiga (dapagliflozin), a sodium-glucose co-transporter 2 (SGLT-2) inhibitor that works independently of insulin secretion by promoting excretion of sugar through the kidneys. Clinical trials have shown that Forxiga improves blood glucose control either alone or in combination with other diabetes drugs, and its effect is sustained up to 102 weeks.
However, dapagliflozin did not fair well with the FDA Advisory Committee and FDA due to the incidence of liver toxicity and breast and bladder cancer risk resulting in the FDA asking for more data and possibly more clinical trials.
The European Medicine Agency however, has endorsed dapagliflozin weighing the benefits against the risk and the need for new treatments options. The EMA will maintain close observations of the risks and requested that the companies conduct an epidemiological study of Forxiga. A number of companies also working on SGLT 2 inhibitors are watching BMS/AZ’s progress very closely.
“Given the complexity of diabetes and the diversity of people it touches, what’s needed is nothing less than a vast new wave of innovation. This will require multiple paths of research that lead us to new and better options for managing diabetes in every stage of life,” said Lechleiter.
New Guidelines for Diabetes Management
The recently updated guidelines recommend that doctors take a patient-centered focus rather than targeting everyone’s blood sugar to a standard targeted level. The goal of a very low blood-sugar level might be appropriate for a younger person but older patients might do better with a less aggressive approach according to guidelines published in the journal Diabetes Care.
Blood sugar is typically defined as being under control for diabetic patients when hemoglobin A1c or HbA1c is below 7%, according to the American Diabetes Association (ADA). Under the new guidelines, this level is still desirable. But younger, newly diagnosed, and motivated patients with a long life expectancy the aim is for an even lower level closer to 6%, according to the recommendations. This aggressive therapy is expected to keep the disease from progressing further.
For older patients vulnerable to severe hypoglycemia, or those who may already have advanced cardiovascular disease, less stringent targets of up to 8% or even a little higher would be sufficient, according to the guidelines. This may also reduce the risk of side effects from medications.
The goal of the current guidelines is to maintain a patient’s blood-sugar level while keeping up with the progression of the disease. But researchers at University of Texas (UT) Southwestern Medical Center in Dallas argue that it’s more beneficial to hit the disease early and hard as demonstrated in a small trial.
The progression of diabetes is usually managed through three or four treatment tiers with insulin injections being the final step in controlling their blood sugar. Researchers at UT Southwestern Medical Center argue that this current treatment strategy does little to change the disease progression when the patients’ own insulin-producing beta cells are still exposed to high blood sugar and the goal should be to preserve the function of the beta cells.
Gordon Weir, a researcher at Harvard-affiliated Joslin Diabetes Center, Boston, believes a strategy using short-term insulin treatment-a couple of weeks or months-to drive blood sugar back to safer levels, may eventually prove effective and become a treatment strategy.
While innovators have learned that treating diabetes early and aggressively is beneficial long-term, reimbursement policies by the insurance companies may stifle patient-centric and aggressive treatment strategies due to cost issues.
If we are ever going to get closer to personalized medicine, acceptance of higher costs upfront to achieve cost-saving long term will have to be advocated and supported in finding the best treatment for diabetics as individual by phenotype. For insurance companies, unless these new aggressive treatment strategies show better outcomes and cost-saving, they will stick to the current guidelines and treat with cheaper medications first. Who is going to support these studies? One can’t expect the industry to run trials, since the outcomes studies are not proving that a new drug will work; it’s a paradigm shift in the management or treatment of diabetics with the same drugs.
In order to show better outcomes and cost-savings, physicians must be able to freely treat patients in a way they feel is best and neither physician nor patient should be penalized (not being reimbursed) for doing things outside of the current guidelines.
What are your thoughts? Please post your comments.
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