American Diabetes Association 68th Scientific Sessions – San Francisco (June 6-10)

When every fifth taxi in downtown San Francisco is carrying an ad for Byetta, FlexPen, or FreeStyle meters, you know the American Diabetes Association (ADA) is in town. Over 20,000 physicians,diabetes educators, and company representatives descended upon our beautiful city by the bay (home of diaTribe headquarters) for five intense days at the ADA’s 68th Scientific Sessions. diaTribe was right there attending sessions, talking to experts, and exploring the exhibit floor to bring you the latest news, views, and reviews from this mammoth meeting.

It is probably easiest to think of this meeting in five parts: the famous Banting Lecture (named for Nobel Laureate, Frederick Banting, a discoverer of insulin); the Presidential Lecture; the results from three landmark clinical trials (ACCORD, ADVANCE, and VADT); the many symposia with updates on progress in diabetes devices and drugs respectively; and the exhibition floor. This issue’s Learning Curve is devoted to a more detailed discussion of the three landmark trials named above. Below are some of our other Conference Pearls from the meeting.

banting lecture – dr. ralph defronzo shakes it up!

Dr. Ralph DeFronzo of the University of Texas Health Science Center and recipient of the 2008 Banting Medal for Scientific Achievement had the honor of delivering this year’s Banting Lecture. There are hardly higher accomplishments in diabetes. One of Dr. DeFronzo’s key messages was the need for earlier interventions in treating diabetes. He explained that by the time people are diagnosed with type 2 diabetes, they have often already lost 80% of their beta cells, the insulin – producing cells in the pancreas. He argued that pre-diabetes should be treated more aggressively before it turns into diabetes.

In what we saw as a defining moment at the conference, Dr. DeFronzo also challenged the idea that type 2 diabetes is a distinct entity from prediabetes. Typically, people who are at risk of developing type 2 diabetes are thought to go through several stages of impaired glucose tolerance (i.e. prediabetes) before reaching the ‘disease’ state of type 2.

However, Dr. DeFronzo believes that labeling these stages as a stepwise progression from normal glucose tolerance, to impaired glucose tolerance, and finally to type 2 diabetes, is rather arbitrary. He proposed thinking of the process as a continuous progression and argued that patients should be treated much earlier in the process and with interventions that can help prevent the death of insulin-producing beta cells. In summary, strive for normal glycemia as early as possible.

Finally, in a provocative conclusion, Dr. DeFronzo criticized the ADA’s treatment guidelines, which recommend lifestyle changes and metformin as initial therapy for type 2 diabetes. He suggested instead that we should begin treatment with a triple combination of drugs: metformin, exenatide (Byetta), and a thiazolidinedione (TZD; such as Actos or Avandia). Dr. DeFronzo’s rationale for multiple drug therapy was to simultaneously treat the multiple organ dysfunctions that contribute to diabetes and at the same time protect surviving beta cells, and possibly augment them. In combination, the three drugs he recommends may help to slow the progression of diabetes and may work without causing weight gain (Byetta prompts weight loss in about 80% of patients who take it, and this may “cancel out” weight gain caused by the TZD). None of the drugs used in Dr. DeFronzo’s combination cause hypoglycemia, a major benefit in his perspective. Dr. DeFronzo’s personal treatment algorithm was controversial since there are no studies showing long-term effects of Byetta - it is a relatively new drug. Additionally, TZDs have been criticized for their association with increased risk of swelling, heart failure, weight gain and bone fractures. Research suggests that these problems are minimal when the drugs are taken earlier and in lower doses. We await information on Dr. DeFronzo’s ongoing clinical study on this subject.

When we asked Dr. Jay Skyler of the University of Miami, one of the leading thinkers in diabetes, for his opinion on the lecture, he gave it high praise it for blending science with potential clinical implications in a scientifically sound and understandable way: “Although I have not been a TZD user (because I don't like weight gain), the arguments persuaded me to re-think that in the context of early treatment with triple therapy of metformin, exenatide, and a TZD, a circumstance in which metformin and exenatide might prevent TZD weight gain. If scientific evidences from an ongoing trial proves that Dr. DeFronzo’s approach is better, it may profoundly influence the future treatment of type 2 diabetes.” See Learning Curve in issue #1 and #8 for more on exenatide, and #6 for more on TZDs.

presidential lecture – dr. john buse defends the ADA

During his lecture, Dr. John Buse, of the University of North Carolina, Chapel Hill and current president of the ADA, defended the ADA’s conservative approach to setting the treatment standards for diabetes care in the US. He acknowledged the tremendous progress we have made thanks to the expanded toolbox of drugs and devices now available to assist with diabetes management. He said, “Since the 1950’s, diabetes has been transformed from a disease of disability and death to a disease that is treatable and has a relatively good prognosis.” This is evidenced in the 2007 diabetes statistics from the Centers for Disease Control and Prevention (CDC) that note that diabetes moved from sixth place to seventh place in terms of leading causes of death in the US.

Dr. Buse explained that it is the ADA’s responsibility to clearly identify which of its recommendations are based on scientific evidence and which are based on “expert opinion” – medical practices based on singular experiences of physicians and not on larger, formal studies. For example, the current ADA guidelines are ambivalent about self-monitoring of blood glucose (SMBG) in type 2s not on insulin. The fine print notes that it “may be useful.” This is because there are few studies conclusively showing the value of testing in this patient population. This doesn’t mean that it is not useful – in fact, Dr. Buse condemned some poorly designed studies that have suggested that SMBG in type 2s should be used less frequently – but it does mean that on this topic the ADA has only expert opinion to rely on. If patients don’t know present blood sugar levels, they will be hard-pressed to plan food, exercise, and medication to obtain suitable future blood sugar levels. That said we take the point that more good studies are needed in this area.

He concluded his presentation with a discussion of rapidly increasing diabetes costs and the pressure to contain them. The ADA, being the nation’s leading voluntary diabetes health organization, has a responsibility to stick to incontrovertible facts in its recommendations and to avoid being influenced by marketing evidence. Nonetheless, the argument is not just about cost, but also about quality of care. "We need to change the dialog from restricting dollars to increasing care." diaTribe certainly agrees with this sentiment particularly since we are using half of the $116 billion spent to directly treat diabetes, on treating complications. We urge more spending on earlier treatments so as to avoid the costly long-term complications seen today.

what’s new with diabetes devices

This year’s meeting had a greater focus on diabetes drugs than devices. Many working in the field of diabetes devices are eagerly awaiting the results of the Juvenile Diabetes Research Foundation (JDRF) CGM trial. The hope is that positive results from this trial will prove conclusively what many of us have believed for ages – the value of CGM and the need for better reimbursement for the technology and for education to teach patients how best to use it. We hope to see some preliminary results later this summer.

One of the recurring debates at this year’s meeting was about whether blood glucose testing is necessary or even helpful in type 2s not on insulin. We believe this debate stems at least partially from patient and physician worries about the cost of blood glucose testing. We wish that as much attention, if not more, were paid to the cost of treating the complications of poor diabetes control. One speaker on this issue noted, “If you can measure it, you can improve it – but if you measure it, you must do something about it.” This highlights the idea that self-monitoring of blood glucose is only effective when patients are empowered to act based on their results.

In a compelling presentation, Dr. Lois Jovanovic of the Sansum Diabetes Research Institute suggested that the ADA should consider stress as a fourth focus point in diabetes management, in addition to exercise, diet, and insulin. She named three different types of stress – psychological, physical, and hormonal – that vary in intensity from person to person. She asked that physicians take this into account when dosing insulin for their patients. Stress reduction is difficult to address for many, but it might help to give it some extra thought as part of your diabetes management.

A recurring message on the subject of CGM was the need for both patients and healthcare providers to set realistic goals and expectations. Dr. Bruce Buckingham of Stanford University characterized CGM as a behavior modification tool – not a magic cure for diabetes. Many presenters emphasized that patients must interact frequently with the device and take appropriate actions based on their readings to benefit from CGM data. One tip: if you have a CGM, try using your receiver as a replacement for your watch so you interact with it more often. Studies have shown greater benefit in patients who interact more frequently with the device and make appropriate changes based on the readings.

To cap off the device section, we were very excited about a poster presented at the meeting showing that safe and reliable use of the DexCom SEVEN CGM sensor for up to 10 days. We hope to see this device receive FDA approval for 10-day use soon.

update on diabetes drugs – new incretins and more

There was a tremendous amount of excitement about the class of diabetes drugs called incretins (see Learning Curve in issue #1 and #9, and Test Drive in issue #3). In fact, there were so many sessions devoted to this topic that ADA President Dr. Buse opened one of his incretin talks saying, “If you haven’t heard of the word exenatide [Byetta] by now, you should contact the ADA organizers and ask for your money back.”

You may have heard about or even used Byetta or Januvia - the only two FDA-approved incretin drugs on the market in the United States for the treatment of type 2 diabetes. A large part of the excitement at ADA centered on long-awaited test results from a newer set of incretins that require less frequent administration. These drugs are formulated to enter the bloodstream more slowly once they are injected. Currently, exenatide (Byetta) is injected twice daily, but the new formulation of exenatide being developed by Amylin/Eli Lilly will only require a once-weekly injection. Data presented on this new drug, which we expect to be out in 2010, showed a 2% reduction in A1c. Liraglutide (Novo Nordisk), another incretin drug in development, will require a once-daily injection with a smaller needle than for once-weekly exenatide. We are always happy about new, safe, and effective alternatives for improving diabetes management.

Data presented at ADA suggested that both exenatide once-weekly and liraglutide provide significant decreases in A1c and body weight with minimal hypoglycemia. Nausea was reported as the predominant side effect. Note that neither is yet FDA approved.

Another presentation that we thought was interesting was on type 2 use of Symlin, in combination with basal insulin. Though this combination isn’t yet approved, the weight loss and A1c reductions were impressive. See Test Drive in issue #2 and #8 for more on Symlin.

We also enjoyed learning more at the meeting about a new drug called alogliptin. This drug is a DPP-4 inhibitor (like Januvia), and from the data we saw at the meeting, we think that it is almost exactly the same as Januvia. The drug is currently being reviewed by the FDA, and could be on the market in about a year.

The meeting was also an excellent opportunity to learn about some of the new types of drugs that are being developed to treat diabetes. Most of these drugs are being studied for type 2 diabetes only, but a few drugs in development including SGLT-2 inhibitors could potentially be used to treat type 1 diabetes as well (as an add-on to insulin). To learn more about SGLT-2 inhibitors, see Learning Curve in issue #8. Because most of these new drugs are in earlier stages of development, we think that it is too soon to know whether they will prove to be safe and effective for treating diabetes. Nonetheless, we were happy to see so much progress in diabetes research, and after hearing about all of the new drugs in development we are very optimistic that even better therapies for diabetes are on the way. Stay tuned…