NewNowNext October 31, 2011

Degludec and degludecPlus Submitted for Approval in the US and Europe

degludecPlus, a fixed-dose combination of degludec (an ultra-long-acting basal insulin) and mealtine insulin recently submitted by Novo Nordisk for regulatory approval.

In October, Novo Nordisk announced that it had submitted its two new “next-generation” insulin products for approval in both the US and Europe (and Japan to follow soon!). The first product, called degludec, is an ultra-long acting basal insulin. The second product, called degludecPlus, is a fixed-dose combination of basal and mealtime insulin (70% degludec and 30% NovoLog). Overall, in studies in people with type 1 and type 2 diabetes, degludec was demonstrated to provide similar improvements in blood glucose control as Lantus – the currently leading basal insulin – while also reducing the rate of overall and nocturnal hypoglycemia (see NewNowNext in diaTribe issue #33). This lower rate of hypoglycemia is thought to result from the drug’s long (42 hours or more) and consistent action in the body. One study found that degludec’s long duration of action makes it possible to dose the drug at different times each day (i.e., in the morning one day, the evening the next day, the morning the day after that) without sacrificing effectiveness and safety. Although we imagine that dosing at roughly the same time each day would make sense for most people, having the flexibility to vary the time of day when needed could be positive for patients. The opportunity to dose degludec flexibly would be an improvement over current basal insulins, which require dosing at the same time each day to maintain sufficient insulin levels in the body and to avoid hypoglycemia. Finally, degludec will also come in a U-200 version (twice as concentrated as usual). The U-200 version will help reduce injection volumes for people with greater insulin requirements. If all goes according to plan, both degludec and degludecPlus may be approved in both the US and Europe in the second half of 2012. --BK

GLP-1 Agonists Now Approved for Use with Lantus and Levemir

Over the past several years, the use of GLP-1 drugs (such as Byetta and Victoza) together with basal insulins (such as Lantus and Levemir) as a treatment for type 2 diabetes has been a hot topic among healthcare providers. For several reasons, this combination therapy makes a lot of sense: 1) the weight loss provided by GLP-1 agonists can help reduce (or overcome) the weight gain associated with long-acting insulin therapy; and 2) GLP-1 agonists and basal insulins help improve blood glucose control in complementary ways. Basal insulins act over a long period of time at a constant rate to cover background (between meal) insulin needs. Meanwhile, GLP-1 agonists cause insulin secretion only when blood glucose levels are high, effectively lowering post-meal blood glucose spikes without increasing the risk for hypoglycemia. Last year, a study examining Byetta in combination with Lantus confirmed much of this thinking, as people with type 2 diabetes achieved greater reductions in A1c and experienced weight loss (instead of weight gain) with both therapies versus Lantus alone. Although the use of a mealtime insulin (such as Apidra, Humalog, or NovoLog) with a basal insulin attempts to accomplish the same exact goal, mealtime insulins typically cause weight gain and significantly higher rates of hypoglycemia (because their action is not dependent on blood glucose levels).

We were excited, then, to hear that two GLP-1 agonist and basal insulin therapy regimens were recently approved for use by people with type 2 diabetes. In the US, Byetta is now approved for use alongside Lantus, and in Europe, Victoza is approved for use with Levemir. Although we had learned through conversations with the diaTribe advisory board that the “off-label” use of GLP-1 agonists with basal insulins was quite common before these approvals were granted, we believe that Byetta and Victoza could become even more attractive alternatives to mealtime insulins as reimbursement improves (the combination had been rarely covered by insurance companies in the past) and healthcare provider familiarity with this combination use expands. There are also a number of other exciting GLP-1 agonist/basal insulin combination products in development (some of which may only be given in one shot per day!). For more information on these products as well as a more detailed account on the use of GLP-1 agonists with basal insulins, please see the NewNowNext column in diaTribe issue #29. --BK

New Treatment for Diabetic Macular Edema Available in Europe and Canada

Eye diseases leading to blindness are consistently ranked among the greatest fears of people with diabetes, and the most common of these eye diseases is called diabetic retinopathy. Indeed, in the US it is estimated that 40% to 45% of people with diabetes have some form of the condition. Diabetic retinopathy involves damage to blood vessels around the retina (the part of the eye that senses light and color), which can lead to blindness in several ways. For example, in diabetic macular edema (DME), diabetic retinopathy causes blood vessels to leak fluid into the macula, the part of the retina that is responsible for sharp, straight-ahead vision. The fluid causes the macula to swell and leads to vision impairment. Up to 75,000 new cases of DME develop each year in people with diabetes, and the consequences are dire – DME is a leading cause of blindness among working-age Americans. Currently, the gold standard for DME treatment is laser surgery, which involves sealing up the leaking blood vessels to reduce the amount of fluid around the macula. In studies, laser surgery reduced the risk for moderate vision loss by 50% over three years, but the operation can also be expensive and debilitating – especially over the long term. However, a new and potentially more effective treatment was recently approved in both Europe and Canada: a drug called Lucentis. Made by Roche (the makers of Accu-Chek strips) and sold by Genentech in the US (and Novartis internationally), Lucentis is already used to treat other eye conditions, including wet age-related macular degeneration (wet AMD). It is injected monthly or less frequently into the eye, where it works by blocking the activity of a molecule (VEGF) that promotes blood vessel growth and blood vessel leakiness. In European studies, Lucentis provided people with DME greater improvements in visual acuity (measured by the number of letters read on an eye chart) versus laser therapy or non-active injections (the control treatment) after one year. More recently, two-year studies conducted in the US have shown that Lucentis improves the eye function of people with DME compared to placebo (inactive) injections. In all these studies, Lucentis has been found to be generally safe and well tolerated; the major downside seems to be price, roughly $2,000 per shot, before insurance. (Avastin, a drug similar to Lucentis that is approved for treatment of cancer, is already used ‘off-label’ by some doctors to treat DME; it is dramatically cheaper per injection, but its safety and efficacy have not been as thoroughly investigated.) Excitingly, Lucentis itself is now on track for use in DME in the US. Earlier this month, Lucentis was submitted to the FDA for the treatment of DME, placing a possible approval around the summer of 2012. --BK

Get involved! IDF’s World Diabetes Day

Here at diaTribe, we are constantly inspired by the huge number of organizations working to improve the lives of people with diabetes. On November 14, the IDF will host World Diabetes Day in more than 160 countries worldwide. The date marks the birthday of Frederick Banting, who first discovered insulin in 1922 along with Charles Best. A core part of World Diabetes Day involves lighting up monuments blue – the color of IDF’s blue circle, the global symbol for diabetes. In 2010 alone, over 900 monuments and buildings in 84 countries were lit to raise awareness of diabetes, including the Metreon right here in San Francisco (see NewNowNext in diaTribe #27). For those in the San Francisco Bay Area, please join diaTribe at this year’s World Diabetes Day on November 14 at 5:30 pm in a blue-lit Union Square. Attendees will attempt a Guinness World Record for the largest hula hooping activity ever (114 people at one time swirling their hips on blue hoops)! The event will also include music, inspirational talks, refreshments, a diabetes resource fair, and more. To sign up and to receive more information, visit http://www.jdrftalk.org/wddsf. To learn more about World Diabetes Day in general, including events in your area and how to light up a monument, visit IDF’s website at http://www.idf.org/worlddiabetesday. --AB

EndoBarrier Device Holds Promise for the Treatment of Type 2 Diabetes and Obesity

GI Dynamics' EndoBarrier Gastrointestinal Liner.

Recently, increasing evidence has suggested that weight-loss surgery (called “bariatric surgery”) can help improve type 2 diabetes management (or even cause its reversal) regardless of the weight loss achieved (see our NewNowNext in diaTribe #18). Bariatric surgery has historically been reserved as a last resort for obese people with a BMI (Body Mass Index) greater than 40 kg/m2 (e.g., 5’7”, 250 pounds) or a BMI greater than 35 kg/m2 (e.g., 5’7”, 190 pounds) with other health conditions. However, some scientists, physicians, and organizations (including the International Diabetes Federation) are now recommending that these procedures be considered in people who are less obese and have type 2 diabetes (see our NewNowNext in diaTribe #32). In particular, one of the more popular procedures performed in the US, called gastric bypass (a procedure that reduces the size of the stomach and reroutes food away from part of the intestine), has demonstrated profound improvements in type 2 diabetes, including its complete reversal in about 90% of people. However, while the potential benefits of surgery are high, so are its risks, with the possibility for long-term health consequences (such as nutritional deficiencies), reoperations, and death (roughly one of every 200 people who undergo gastric bypass die within 30 days of surgery).

Enter the EndoBarrier^® Gastrointestinal Liner, a device that attempts to mimic some of the effects of gastric bypass without requiring surgery, thereby capturing some of its benefits while reducing risk. The EndoBarrier is inserted through the mouth and secured just below the stomach and into the start of the intestine. Implanting the device takes approximately 30 minutes under general anesthesia, while its retrieval takes about 15 minutes. The EndoBarrier is designed to act as a physical barrier between food and the walls of the intestine to delay digestion and bring about other hormonal improvements in metabolism. In a study in Brazil, individuals (with average BMI of 44.8 kg/m2, e.g., 5’7” and 290 pounds) with EndoBarrier implants achieved an impressive A1c reduction of 2.3% from a baseline of 8.9%. This reduction was obtained after a year of using the EndoBarrier, and it was sustained to six months after removal of the device. In another study in Chile, 12 months of EndoBarrier treatment produced an average of 20% total body weight loss (about 50lbs). Six months after removal, individuals who used the EndoBarrier maintained as much as 75% of the weight they lost during the treatment period. While the A1c-lowering effects of the EndoBarrier are encouraging, the small sample size (13 individuals) and short follow-up duration make it hard to know how effective the device will be in the long term and for less obese people with type 2 diabetes. But the high weight loss and A1c reduction could serve as an effective ‘kick start’ to a simultaneous lifestyle improvement program.

While the ease and reversibility of the procedure are preferable compared to bariatric surgery, we await more information on patient experience. Some people in the studies have reported early (usually temporary) nausea and pain caused by the expansion of the anchor that secures the liner to the intestine and (rarely) the movement of the device itself – although the overall scale and severity of side effects are much better than bariatric surgery.