NewNowNext December, 2010
FDA Advisory Committee Recommends Approval of Weight-Loss Drug Contrave
Contrave, a novel weight-loss drug made by Orexigen.
After a day of deliberation earlier this month, a recent FDA advisory committee voted 13 to 7 to recommend approval of Contrave, a novel weight-loss drug made by Orexigen. The FDA now has until the end of January to make a final decision on whether to approve the drug or ask for additional data. Contrave is the third obesity drug to face the FDA advisory panel in the past six months but the first to receive a positive nod from the committee in over 10 years – a remarkable statistic, given the obesity epidemic. The other two drugs (Lorqess and Qnexa) were both voted down due to various safety concerns and have since received negative decisions from the FDA, which requested additional analyses of data for Qnexa and additional animal studies for Lorqess. The outcome of the Contrave panel was a pleasant surprise and represented a shift in opinion among the panelists. For the first time in recent history, members of the committee referenced the need for therapies that target obesity and obesity-related conditions, such as high blood pressure, high cholesterol, and type 2 diabetes (all three obesity drugs have demonstrated glucose-lowering effects). During the committee's discussion about Contrave, the primary concerns were related to the drug's tendency to marginally increase heart rate and blood pressure, compared to those taking a placebo pill. The panelists voted 11 to 7 to recommend requiring a dedicated cardiovascular "outcomes" study following FDA approval, rather than requiring it prior to approval, which would delay Contrave by at least two years. (An "outcomes" study would be a human trial that determines the long-term risk of the drug on the heart.) Going forward, the FDA will review the votes and discussion of the Advisory Committee members before making a final decision on whether to approve Contrave (expected by January 31, 2011). Please see NewNowNext in diaTribe #18 to learn more about all three late-stage weight loss drugs (Arena's Lorqess, Orexigen's Contrave, and Vivus' Qnexa). --ST
Medtronic Launches New Pump/CGM Analysis Software for Healthcare Providers
Medtronic's CareLink Therapy Management Dashboard provides a one-page summary of insulin and glucose data.
Although no one ever said insulin pump management was easy, we’re very happy that new tools are emerging that can make pumping easier and better. We have often wondered whether most people had pumps that were under-optimized. Pumps require careful setup of several parameters (basal rates, insulin:carb ratios, sensitivity factors), and it’s been difficult over time for patients to get all these rates and ratios to work together as well as possible. Additionally, after all this attention to detail, most pumpers have neither the patience nor time to use advanced pump features like square/dual-wave bolusing and basal patterns. Thankfully, diabetes device companies have developed data management programs to help people with diabetes and their healthcare teams visualize information, identify trends and take action. For example, Animas has ezManager Max, Insulet has the OmniPod Pathfinder system, and Medtronic has two types of software for managing pump and/or CGM data: CareLink Pro for healthcare providers and CareLink Personal for individuals. We hear especially positive remarks from healthcare providers about Medtronic’s software and wanted to do a little exploration on the highly-touted newest system, the CareLink Pro 3.0. (And please stay tuned – we’ll have a Test Drive using the software in 2011 since we hear it can really help establish and refine basal rates and all the ratios on pumps.)
To use these systems, the patient connects the devices to a computer (often easier said than done), and the program downloads all the data, displays it and records it. Then the fun begins: healthcare providers and/or patients interpret the data, which is then ideally used to change therapy or behavior. Although the data summaries from these programs can be very helpful, it does take some time. Whether you’re a novice pump-user or an experienced endocrinologist, optimizing glucose control can be tricky and time-intensive.
Medtronic’s recently launched CareLink Pro 3.0 software is a welcome step forward in data analysis and presentation, offering two important features for healthcare providers. (These new tools require both pump and sensor data; for providers whose patients are using only a pump or only CGM, the CareLink Pro software will function as before.) The first new tool is the Therapy Management Dashboard, a one-page summary of insulin and glucose data. The Dashboard brings together information from various pages of previous CareLink Pro reports: overlays of sensor glucose curves, levels of basal and bolus insulin throughout the day, average carbohydrate intake (if someone has used the pump’s Bolus Wizard to calculate mealtime insulin dosage), and more. The Dashboard also includes topics such as Bolus Wizard overrides, estimated A1c, and – perhaps most helpfully – the patterns of hypoglycemia and hyperglycemia during different times of day.
The Episode Summary displays hypoglycemia and hyperglycemia related events, along with ideas for how to improve control.
The valuable other new feature, the Episode Summary, analyzes highs and lows in more detail. The Episode Summary's charts display hypoglycemia and hyperglycemia related events, along with ideas for how to improve control. The Episode Summary analyzes up to 28 different event types, ranging from "dawn phenomenon" to "carbohydrate entry of more than 80 grams" to "delayed site change." For example, if someone's low blood sugars were often the result of overcorrecting high blood sugars, the summary for the provider might say: "Consider assessing your patient's insulin sensitivity factors. Consider counseling your patient on the management of hyperglycemia."
We would like to see these kinds of decision-support features included in CareLink Personal too, so that pump users can access them directly. In the short term, the FDA blocks software that offers this level of analysis to non-healthcare professionals; companies will have to prove whether their programs are reliable enough for individuals to use on their own. In the long term, however, we are confident that analytical systems like these will help control the artificial pancreas. Generally speaking, we think that pump and CGM software is unnecessarily complex, especially with regard to uploading data from devices in the first place. Still, given the potential benefits of Medtronic's new program – saving clinicians' time, sparking productive conversations, demystifying pump management – we think CareLink Pro 3.0 could help make life healthier (and simpler) for many people with diabetes. --JS
Integrated Device to Feature Next-Generation Insulet OmniPod in Combination with DexCom Continuous Glucose Monitor
In the integrated system, continuous glucose readings from the DexCom sensor will be sent wirelessly to the OmniPod PDM.
As we wrote in NewNowNext in diaTribe #24, Insulet and DexCom submitted their combined insulin pump-continuous glucose monitor (CGM) device for FDA approval during an especially difficult time for device regulation. Sure enough, the FDA responded with a formal written response requesting substantial additional information including additional human clinical trial data concerning the safety of insulin delivery by the system. But the setback is a positive in some respects because it means the combination product will now feature the second-generation version of the OmniPod, which we believe will be approved in 2011. The new pod will be a third smaller and 25% lighter: great news for those who will ultimately use the combination product. The original plan was for the first-generation OmniPod to be paired with DexCom’s current CGM sensor, the SEVEN PLUS; however, at the time of this writing, it is not known version of the DexCom CGM will be incorporated into the Insulet insulin pump. Unfortunately, based on recent FDA activities and the public statements of the companies, it is highly unlikely that we will see a combined Insulet/DexCom product in 2011. Here's hoping that 2011 nonetheless sees progress on this integrated device, and that the picture looks better at the end of the coming year.
Santarus Launches Cycloset, A Novel Drug Treatment for Type 2 Diabetes
Cycloset, Santarus' novel, weight-neutral, glucose-lowering drug for type 2 diabetes was recently launched in November.
In mid-November, Santarus Inc. announced the launch of Cycloset, a novel, weight-neutral, glucose-lowering drug for type 2 diabetes. Cycloset is a quick-release formulation of bromocriptine, which acts directly on the brain by binding to dopamine receptors (the binding of molecules to dopamine receptors is responsible for a number of effects in the body, including the modulation of insulin resistance in some animals). Although the specific means by which Cycloset brings about improvements in glycemic control remain largely unknown, in a clinical trial, the drug was shown to lower A1c by 0.6% to 0.9% when added to other oral antidiabetic medications, from a base of 8.3%. In addition, a clinical study of Cycloset found that, when taken once daily within two hours of waking, Cycloset can provide reductions in post-meal glucose levels throughout the day. This improvement happens without increasing plasma insulin concentrations, suggesting a possible effect on insulin sensitivity. Importantly, data from clinical trials for Cycloset suggest that it may even lower cardiovascular risk – a huge benefit considering most people with type 2 diabetes are at increased risk for heart disease. Safety data have been encouraging for Cycloset, and the active component in the drug (bromocriptine) is generally regarded as safe after many years of approved use for the treatment of Parkinson's disease. Considering Cycloset's modest efficacy in lowering blood glucose levels, its safety profile, and its novel mechanism, the drug seems like a candidate that could have some valuable use in combination therapy for type 2 diabetes. --VW
Valerita's V-Go Disposable Insulin Delivery Device.
Valeritas Receives FDA Clearance to Market Its V-Go Disposable Insulin Delivery Device and Plans to Launch in 2011
Medical technology manufacturer Valeritas announced earlier this month that it received FDA clearance to market its V-Go Disposable Insulin Delivery Device, which delivers basal-bolus therapy for adults with diabetes. From the onset of its development, the V-Go was designed with the type 2 patient in mind. We think of the V-Go like a substitute for vials/syringes and pens more than as a pump. The non-electronic, mechanical device automatically administers insulin at a preset basal rate over 24 hours (after which time the device stops and must be replaced), and users can also deliver two-unit boluses by a manual two-step process. While the V-Go is approved for “adult patients requiring insulin,” Valeritas will be targeting this new device primarily to those with type 2 diabetes because the preset basal rates are appropriate for those who do not need to vary their basal rates, and because the two-unit boluses may not be flexible enough for many people with type 1 diabetes. The V-Go will be available in three different preset basal rates, reflecting basal delivery of either 20, 30, or 40 units per day, with each version allowing up to 36 additional units for on-demand bolusing, i.e., up to 18 pushes daily, at which point the device has a “lock-out” feature which signals patients that no more boluses can be given. Effectively, the V-Go allows for the delivery of up to a total of 56, 66, or 76 units of insulin per day, depending on the basal rate, which covers approximately 70% of people with type 2 diabetes currently on insulin therapy. The V-Go weighs roughly one ounce when the reservoir is full; by comparison, Insulet's first-generation OmniPod weighs 1.2 ounces when full. The V-Go's dimensions (2.4” x 1.3” x 0.5”) are slightly smaller than the current OmniPod's (2.4” x 1.6” x 0.7”). Insertion is with a 30-gauge stainless steel needle; the device can exert high pressures through the stainless steel needle, which should eliminate or largely reduce the risk of occlusions.
In our view, the major advantages of Valeritas' device are its simplicity, discretion, and convenience: an automatic preset basal rate (without the need for a hand-held controller), and mechanical bolusing that can be done through the patients' clothing (without the need to keep track of pens or syringes, an obstacle that leads many patients to administer insulin only at home). As it is fully mechanical, this could be an advantage as long as it is easy to change; we look forward to hearing how patients and healthcare providers like it. Given the potential market for Valeritas' versatile product, much will ride on reimbursement decisions for fast-acting insulins and for the device itself. We look forward to hearing more about the V-Go. --KC
DPP-4 Inhibitor/Metformin Combination Once-Daily Pill Kombiglyze Gains FDA Approval
Kombiglyze, a pill combining DPP-4 inhibitor Onglyza and metformin.
In early November, Kombiglyze, a pill combining DPP-4 inhibitor Onglyza and metformin, was approved by the FDA for type 2 diabetes. Onglyza was approved in July 2010 (for more information, please see NewNowNext in diaTribe #17). The DPP-4 inhibitor class of drugs, which includes Merck's Januvia, Bristol-Myers Squibb/AstraZeneca's Onglyza, and Novartis' Galvus (approved outside the US), has very few side effects based on the safety data that has been shown to date. These drugs can be combined with metformin into a single combination pill (Januvia's metformin combination is called Janumet, and Galvus' metformin combination is called Eucreas). Kombiglyze represents the first DPP-4 inhibitor/metformin combination that can be taken once-daily, while Janumet and Eucreas must be taken twice-daily. Kombiglyze may also offer the additional benefit of reduced digestive discomfort because it includes a particular type of metformin, called "metformin extended-release," or metformin XR (which also enables once-daily dosing). While individual studies with different types of metformin have confirmed that metformin XR is associated with reduced digestive side effects, specific studies comparing different DPP-4 inhibitor/metformin combinations have not been conducted. We also note that the manufacturer of Janumet (Merck) is planning to submit a once-daily form of Janumet with metformin XR in the US for FDA approval before the end of 2010. In general, other than dosing and the type of metformin, Kombiglyze is largely similar to Janumet; both DPP-4 inhibitor components, Januvia and Onglyza, have demonstrated very similar safety and effectiveness in type 2 patients. For a general overview of DPP-4 inhibitors, please see the Learning Curve in diaTribe #8. For more information on programs that can make Kombiglyze more affordable, please visit AstraZeneca's Prescription Savings program. --ST
Advisory Committee Recommends the FDA to Approve Label Expansion of Allergan's LAP-BAND to Include Lower Body-Mass-Indexes
The LAP-BAND is a weight-loss device that is implanted around the top of the stomach using minimally invasive (laparoscopic) surgery, which effectively creates a small pouch for food at the top of the stomach and delays the passage of food into the lower part of the stomach. As the pouch in the upper part of the stomach fills, it sends signals to the brain telling it that the whole stomach is full. This in turn helps to promote fullness and satiety, with the intent of reducing hunger and food intake, and ultimately bring about weight loss. Ever since the LAP-BAND received FDA approval in 2001, the device has been approved for use in people with a BMI of 40 kg/m2 or higher, or a BMI of 35 kg/m2 or higher with the presence of one or more "serious comorbid conditions" (e.g. type 2 diabetes, high blood pressure). Earlier this month, members of the FDA Gastroenterology and Urology Advisory Committee met to consider expansion of the label for Allergan's LAP-BAND to include lower body-mass-indexes. In a move that surprised some (because the FDA has been so conservative as of late), the committee voted 8-2 in favor of expanding the LAP-BAND's label to include people with a BMI of 35 kg/m2 or higher, and people with a BMI of 30 kg/m2 or higher with at least one or more "comorbid conditions," effectively lowering the BMI requirement for use of the LAP-BAND by 5 kg/m2. Since the majority of panelists were clinicians who regularly treat obese patients, most recognized the need for more tools. However, panel members emphasized that with expansion of the label, long-term safety and efficacy of the LAP-BAND must be monitored carefully. Panel members raised concerns over the durability of the weight loss effect, potential reoperations and complications, and the lack of male and minority representation in LAP-BAND trials – all excellent points in our view. While the FDA advisory committee's vote is certainly a positive indication, the vote is only a recommendation to the FDA, albeit one that the FDA rarely goes against. We look forward to hearing the FDA's final decision shortly. --VW
What about the Parents!?
Often, parenting children with diabetes can be frightening and lonely, and few understand this better than Jeff and Natalie Kolok. With two type 1 children of their own, Jeff and Natalie sought to help other such parents overcome the isolation they often felt by providing them an online community. The result: www.parentingdiabetickids.com. Founded in 2007 and recently expanded, this website offers a number of helpful resources, including a forum in which visitors can reach out and learn from others in nearly 190 different topic rooms (covering subjects from school to travel to insulin pumping); a news page that breaks down relevant diabetes developments for even the most scientifically disinclined; and a resource page that provides lists and descriptions of valuable type 1 diabetes-related books, websites, magazines, tips, and camps. We were also impressed by the "ask our team" page of the website, which allows visitors to ask questions and receive answers from the site's team of diabetes management experts, including one of our favorite diabetes educators and regular diaTribe contributor Gary Scheiner. While the site is still growing, with just over 700 members, we liked its overall warmth and community-like feel, as well as its simplicity and ease of use. --BK
Type-1 University
Noted Certified Diabetes Educators Gary Scheiner and Karen Franey have created Type-1 University, which provides pre-recorded and live 40- to 60-minute courses that can be viewed on PCs, Macs, and smartphones. Special interactive opportunities accompany the live programs, which usually take place on Tuesdays and Thursdays, at 1 PM and 8 PM EST. Each individual seminar costs $29.95. Topics include Mastering Pump Therapy, Advanced Carb Counting, Blood Glucose Control During Sports & Exercise, Weight Loss for Insulin Users, Getting the Most from Your Continuous Glucose Monitor, Strike the Spike: After-Meal Glucose Control, Hypoglycemia Prevention and Management, and Fine-Tuning Basal Insulin. After participating, one student commented: “You can't get this information anywhere else. The Type-1 University instructors don't just teach diabetes... they live with it.” For more information, please visit: www.type1university.com. --MH/KC
Women with Diabetes Unite! Raleigh in the Spring...
Kelly here, the founder of diaTribe. Are you a woman interested in connecting with other women with diabetes and learning more about the unique challenges of diabetes? Then check out DiabetesSisters' national Weekend for Women Conference, April 29 - May 1, 2011 at the Marriott City Center in downtown Raleigh, North Carolina. I'm definitely going and I'd love to see you there! This conference will offer workshops on gender-specific diabetes treatment and management (such as pregnancy, body image, concurrent illnesses, nutrition, physical fitness); information on new methods to improve mental and physical health; views on new equipment and medications; and the opportunity to engage with other women living successfully with diabetes. Singer and entertainer Gloria Loring will appear, very cool. The Conference Exhibit Hall will be open from 8 AM to 5 PM on Saturday, April 30. Conference registration is open to all women with diabetes age 18 and older. Act quickly - this is only open to the first 200 women who register, and last year the conference sold out after just six weeks. Registration will open on January 1, 2011, at 8 AM and must be made online at www.diabetessisters.org.
The conference was fantastic in 2010 and promises to be even better in 2011, led by DiabetesSisters founder Brandy Barnes. Registration for the conference is offered at a subsidized rate of $100 (an amazing deal) and includes all meals and snacks on Saturday (including the Celebration of Strength Dinner), breakfast on Sunday, attendance at all eight educational sessions, and many other giveaway items. A discounted group rate of $99 per night has been secured at Marriott City Center. Hotel reservations can be made using group code DSSDSSA by phone at 1-888-236-2427 or online. DiabetesSisters is a national 501(c)3 non-profit health organization dedicated to advocating for and improving the lives of women with, and at risk of developing, diabetes. For more information, please visit www.diabetessisters.org. --KC