46th Annual Meeting of the European Association for the Study of Diabetes (EASD)

by ben kozak

This past month, the entire diaTribe team had the amazing opportunity to travel to Stockholm, Sweden, to learn about the latest in diabetes research and patient care at the EASD 2010 conference. While our time inside the “Mässan” conference center was filled with excitement, we also thoroughly enjoyed our time exploring this historic city with its winding (and very confusing) roads, beautiful architecture, and shockingly tall inhabitants. We also got our fair share of delicious Swedish meatballs and dill flavored…well, everything. Below, we provide you our key takeaways from this great meeting.

updates on bolus insulin 

Lately, researchers have been trying to find ways to make even better insulin products that reduce the risk for hypoglycemia in between meals as well as excessive rises in blood glucose right after meals. Their strategies have boiled down to making basal insulins that act longer and more consistently and making bolus insulins that act more quickly. (For more information on the history and future of insulin therapy, please see the Learning Curve in diaTribe issue #9). At EASD 2010, we heard the most recent news on the development of ultra-fast acting insulin products. One such product is M

annKind’s Afrezza, an inhaled insulin. Recently, the safety and glucose-lowering effect of Afrezza was compared to a variety of currently available insulin therapy regimens in individuals with type 2 diabetes. Over a two-year period, Afrezza was shown to provide similar levels of A1c reduction and similar weight gain, but promisingly, significantly less hypoglycemia. While no changes in lung function were observed with the long-term use of Afrezza, 29% of individuals that u

sed the product experienced what was termed “mild and transient” cough. We are concerned about this side effect and wonder how mild and transient the cough really is; we were told that it caused very few people to stop taking the medication. Regardless, this is a promising therapy, especially for those that would prefer to inhale their insulin rather than use needles. Afrezza may become available by early 2011.

We also heard about Biodel’s Linjeta (formally called VIAject), another fast-acting insulin. Linjeta is an injectable insulin that uses certain chemical agents to speed its absorption and action in the body. At EASD 2010, we were happy to hear results that confirmed that this new product had a much quicker onset of action and absorption than Humalog in type 1 patients. In a separate study in individuals with type 1 diabetes, Linjeta was shown to provide similar reductions in A1c as regular human insulin, but significantly reduce the risk for severe hypoglycemia and significantly reduce weight gain. Certainly, these results are also promising and we note that similar findings have been found with use of Linjeta in individuals with type 2 diabetes. This product may be approved for use in the US as early as the beginning of November this year. The future certainly does look bright for insulin therapy.

updates on the artificial pancreas

The development of an artificial pancreas continues to be one of the hottest topics in the field of type 1 diabetes, and at the EASD meeting, we had the chance to hear about an interesting study showing how far the technology has come. An artificial pancreas is a “closed-loop system” composed of a continuous glucose monitor (CGM) and an insulin pump that communicate with each other through a computer-based set of instructions. 

This algorithm takes the blood glucose readings from the CGM, calculates how much insulin is and will be needed, and signals the pump to increase, slow, or stop insulin delivery – all without any input from the patient.(For more information on the artificial pancreas, please see Conference Pearls in diaTribe issue #11). Naturally, such a system needs to be designed to respond to those situations where glucose control gets tricky, such as illness, intense exercise, or – as in the study we saw in Stockholm – a “late evening out followed by a sleep-in the next morning”,  a refreshingly European perspective. To simulate this scenario, the study participants were given a large meal and forced to drink several glasses of wine at night and then were not allowed to eat breakfast in the morning. Each participant went through this process twice during a two-week period, once with his or her usual insulin pump settings, and once (either before or after the standard pump night) with the artificial pancreas. Compared to when they used traditional pump therapy, participants on the “closed loop system” spent nearly 25% more time in their target blood glucose range, avoided hypoglycemia at 2 a.m., and eliminated the dawn phenomenon (the rise in blood glucose in the early morning often experienced by individuals with type 1 diabetes).

While this study was relatively short and small, we believe these results to be quite exciting given the substantial challenge presented to the closed-loop algorithm. Although the development of a fully functional artificial pancreas may not come for some time, we believe results from trials like these  indicate that significant progress is being made, and we expect to hear more promising results in the months and years to come.

diabetes, insulin, and cancer?

Is there really a link between the use of insulin and cancer? This question has been featured prominently in mainstream media since last summer when several articles were published in the scientific journal Diabetologia that supposedly found an association between increased risk for cancer and use of the basal insulin Lantus (insulin glargine). We stress that such associations do not prove a cause-and-effect relationship between Lantus use and cancer and many other reputable studies have actually found no such associations – although the newspapers are less interested in reporting them.
At EASD 2010, we heard from several notable scientists on the issue. What is clear is that diabetes increases the risk for developing certain cancers including bladder, breast, colorectal, endometrial, liver, and pancreatic. Diabetes also appears to increase the risk for cancer mortality. Surprisingly, Dr. Hsin-Chieh Yeh, of Johns Hopkins University School of Medicine, said that one of the main causes for this increased mortality risk may be the delays in cancer screening that have been found for individuals with type 2 diabetes – meaning that, once diagnosed with cancer, the disease is in a much later stage and harder to treat. Furthermore, once diagnosed, individuals with type 2 diabetes are more likely to be treated less aggressively. Dr. Yeh noted, and we agree, that this different treatment was very concerning and argued that it will be important from here on out that all patients with diabetes receive standard cancer screening as well as aggressive anti-cancer therapy.

In terms of whether insulin therapy itself contributes to this increased risk for cancer, the jury still appears to be out. Our favorite perspective came from an oncologist, Dr. Michael Pollak. Insulin normally acts to lower our blood glucose levels by interacting with several kinds of receptors in our body. Intriguingly, two of these types of receptors (called the insulin receptor and IGF-1 receptor) are located on cancer cells, and at least in rats, increased insulin levels and increased activation of these tumor insulin receptors are associated with tumor growth. Because of these findings, Dr. Pollak argued that elevated insulin levels, which occur during the early stages of type 2 diabetes as well as with insulin therapy, may cause increased activation of these tumor insulin receptors in humans, causing existing cancers to grow faster or potentially causing benign tumors to turn into malignant tumors. This could ultimately provide an explanation for the greater risk of cancer among individuals with diabetes. Still, he pointed out that no clear proof of this hypothesis exists and that clinical trials are needed. Most importantly, he emphasized that while an increased risk may exist for cancer with insulin use, this risk is small compared to the risks for cardiovascular disease, neuropathy, amputations, and other diabetes complications that emerge from not using insulin and having chronically elevated blood glucose levels. Thus, to Dr. Pollak, while individuals with diabetes should be made aware of the possible associations of insulin and cancer, insulin should continue to be used with confidence.

The Obesity Society

by vincent wu

Recently, we journeyed south to the sunny city of San Diego for the 28th Annual Scientific Meeting of The Obesity Society (TOS), where we learned about the latest developments in obesity treatment, research, and policy. At the meeting, we heard much discussion on the use of GLP-1 agonists (Amylin/Eli Lilly’s Byetta [exenatide] and Novo Nordisk’s Victoza [liraglutide]), and the off-label use of medications for the treatment of obesity and type 2 diabetes, which we share with you below.

glp-1 therapy update

These days, GLP-1s (Amylin/Eli Lilly’s Byetta and Novo Nordisk’s Victoza) are generating a lot of buzz for their abilities to induce insulin secretion when blood glucose levels are high, to promote weight-loss, and to potentially provide heart protection. At TOS 2010, a number of presenters elaborated on the weight-loss effects of GLP-1s. Dr. Steven Chen, Director of Medical Development at Amylin Pharmaceuticals, noted that people with type 2 diabetes in pivotal trials lost an average of approximately 12 pounds over the course of three years on Byetta. Perhaps more importantly, Byetta seemed to have an impressively durable effect, with the curve of weight loss demonstrating a gradual, persistent reduction in weight over three years. Notably, Dr. Chen also presented weight loss data from the several clinical trials for Bydureon (Amylin/Eli Lilly/Alkermes’ exenatide once-weekly), confirming a similar trend in weight loss over 26 weeks compared to Byetta. This was striking in our view, as Bydureon seems much easier to prescribe and to take. (Sadly, Bydureon will not become available commercially for a while due to recent regulatory setbacks.) 

Meanwhile, Dr. Alan Moses, Global Chief Medical Officer of Novo Nordisk, highlighted a study in which high doses of Victoza (liraglutide 3.0 mg) were demonstrated to reduce weight by an average of 22 pounds over 104 weeks in obese adults without diabetes. It is important to note, however, that the 3.0 mg dose is higher than the current doses (1.2 and 1.8 mg) approved for use to treat diabetes. We stress that GLP-1s are not currently intended for use as weight loss treatments. Still, the results above are certainly promising, and if these results are replicated in further clinical trials, we may soon see use of GLP-1s extend beyond diabetes and into obesity and weight management.

off-label use 101: what you need to know

Usually, when drugs are approved for use in the United States, the FDA specifies the medical condition(s) that the drug is intended to treat. However, occasionally, healthcare providers choose to use a medication to treat a condition that it has not yet been approved for by the FDA. This is referred to as “off-label” use of a drug. This is not to say that the medication is necessarily unsafe or ineffective at treating this other condition (although it can be); rather, the company that produces the drug may not have realized during development that its product had these other therapeutic effects and may not yet have provided the FDA with the necessary data from clinical trials to gain approval for their drug to treat this additional condition. (Unfortunately, reimbursement for off-label use is often challenging as a result.)

Currently, with only one drug currently approved in the US for the long-term treatment of obesity, some healthcare providers have turned to off-label prescriptions for their patients in need of pharmaceutical options. During the meeting, after noting that off-label prescriptions are perfectly legal, the past president of The Obesity Society Dr. Louis Aronne, outlined a few practical considerations that should be taken regarding the off-label use of medications. Before using medications off-label, even if your healthcare provider says it’s fine: 1) Be sure your healthcare provider can provide strong scientific evidence supporting off-label use of the medication; and 2) Make sure you fully understand the risks and benefits associated with off-label use before taking the medications. Dr. Aronne mentioned Dr. Arya Sharma’s book, “Best Weight,” as a great reference that provides evidence for or against the off-label use of specific drugs for the treatment of obesity.