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GLP-1 agonists (for example, Byetta, Victoza, and Bydureon) were first approved in 2005 and stimulate the body to produce insulin only when blood glucose levels become too high. Lately, the concept of using a GLP-1 agonist with a basal insulin (such as Levemir and Lantus) has received more attention; the use of this combination to treat type 2 diabetes offers a number of advantages. One advantage is that GLP-1 agonists and basal insulins act in complementary ways to lower blood glucose, meaning that the use of both therapies together may well improve blood glucose control more effectively than either therapy alone. A major advantage of combination GLP-1/basal insulin therapy is that treatment with a GLP-1 agonist can lead to reduced food intake and weight loss, which may help overcome the weight gain typically observed with basal insulin therapy. Moreover, basal insulins act slowly and over a long period of time to cover background insulin needs, while GLP-1 agonists stimulate insulin secretion only when blood glucose levels are high. This makes GLP-1 agonists effective therapies f0r post-meal glucose spikes without increasing the risk for hypoglycemia.
April marked an exciting month for combination GLP-1/basal insulin therapy, with three notable announcements made. The first announcement was that the GLP-1 agonist Victoza was finally approved for use with any basal insulin in the US. The approval was based upon a study that looked at the safety and effectiveness of treating people with Levemir, a basal insulin, who were already using Victoza and metformin. Over 52 weeks, those treated with Levemir achieved an additional A1c reduction of 0.5% over those who were not. The risk for hypoglycemia was higher among those receiving Levemir, although the risk was still low (0.228 episodes per patient year vs. 0.0034 episodes per patient year). Finally, it was shown that the use of Levemir had a minimal effect on weight. Victoza’s approval for use alongside any basal insulin in the US follows the US approval of the GLP-1 agonist Byetta’s use with basal insulin Lantus last October (see new now next in diaTribe #37). In comparison to Byetta, Victoza offers the convenience of fewer injections (once per day vs. twice per day) and the freedom to use with any available basal insulin. To date, no trials have compared the effectiveness of Victoza and Byetta when used with a basal insulin, although some scientists have argued that shorter acting GLP-1 agonists (like Byetta) may offer greater effectiveness because of their greater effects on post-meal glucose levels. Nonetheless, this approval for Victoza is certainly exciting, and we expect reimbursement and access to this treatment option to improve in the months ahead.
The second piece of news this month came from GlaxoSmithKline, which announced positive clinical trial results for its new once-weekly GLP-1 agonist (albiglutide) when used in combination with basal insulin therapy. In the trial, 500 people with type 2 diabetes received either a weekly injection of albiglutide in combination with a daily injection of Lantus or a daily injection of Lantus in combination with mealtime injections of the prandial insulin Humalog. Over 26 weeks, those receiving albiglutide achieved significantly greater reductions in A1c than those receiving Humalog (0.82% vs. 0.66%). Weight loss was also greater among those receiving albiglutide (a loss of 1.16 lbs) than those receiving Humalog (a gain of 1.8 lbs). As expected, the most common side effects among those receiving albiglutide were nausea (13.0% with albiglutide vs. 2.1% with Humalog) and vomiting (7.0% vs. 1.4%). The use of albiglutide in combination with a basal insulin could reduce the number of required injections per week by 13 versus Byetta and six versus Victoza. GlaxoSmithKline has not yet revealed when it might apply for approval for albiglutide as a therapy for type 2 diabetes, but we believe it will likely be in 2013, placing a possible approval in early 2014.
Finally, even further down the road, we also heard an update from Sanofi and Zealand Pharma on their novel pen device that will allow users to inject both Lyxumia (the companies’ once-daily GLP-1 agonist) and Lantus at the same time, eliminating one extra shot per day. Notably, the companies announced that their pen device will allow users to adjust their Lantus dose while receiving the same dose of Lyxumia every time. The device is currently under development, and Sanofi has indicated that trials will begin in early 2013. If all goes well, the device could become available as early as late 2014. Meanwhile, Novo Nordisk is taking an alternative approach to its combination GLP-1 agonist/basal insulin pen device. Instead of allowing users to adjust their insulin dose separately from their GLP-1 dose, the drugs (Victoza and the company’s latest basal insulin called degludec) will always be injected together at a fixed ratio to one another. In other words, if a user reduces the amount of degludec they wish to inject, the amount of Victoza they will receive will be reduced as well. Novo Nordisk has indicated that this approach will still allow over 80% of people to receive the right amount of basal insulin and enough Victoza to be effective in the body. Two phase two trials for this device are underway, which are expected to complete in the second half of this year. Assuming the trials complete as expected, approval may be possible as early as the end of 2013. –BK
Earlier this month, an initial regulatory assessment committee recommended the novel type 2 diabetes therapy dapagliflozin (Forxiga) for approval in Europe. A final decision from the European Medicines Agency (the FDA equivalent in Europe) on whether to approve the drug is expected within three months. Dapagliflozin belongs to a class of drugs called SGLT-2 inhibitors, which lower blood glucose levels by disposing of excess blood glucose through the urine (for more information, please see new now next in diaTribe #35). If approved in Europe, dapagliflozin would become the first SGLT-2 inhibitor to receive approval anywhere in the world.
Dapagliflozin’s recommendation for European approval came as a surprise to some, as the FDA denied approval of the drug in January. While Bristol-Myers Squibb and AstraZeneca (the manufacturers of dapagliflozin) have not discussed in depth the reasons behind the FDA’s rejection, the agency is likely concerned over potential increased risks for bladder and breast cancer as well as the potential for liver damage (for more information, please see new now next in diaTribe #39). The committee that recommended the approval of dapagliflozin in Europe also noted some concerns about the drug’s safety, including cancer risk, but called for these concerns to be evaluated post-approval rather than pre-approval. In the US, the FDA has indicated that additional clinical trial data will be required before it will reconsider approving the drug, and we hope to hear further details from the companies shortly regarding their plans to address the FDA’s concerns. Still, we believe that dapagliflozin’s recommendation for European approval bodes well for its eventual approval in the US. –BK
On April 9, the FDA announced that it had extended the decision date for Vivus’ obesity medication Qnexa by three months to July 17. The agency postponed its approval decision in order to make sure that it has enough time to review Vivus’ proposed Risk Evaluation and Mitigation Strategy (REMS). REMS is the scheme by which the company would provide education to patients, physicians, and pharmacists on the appropriate use of the drug and its associated risks; have measures in place to restrict the drug’s use only to approved sets of patients; and be able to closely monitor the drug’s safety. (As a reminder, the safety concerns with Qnexa are a potential increased risk of birth defects [especially cleft lip or cleft palate] and a slight increase in heart rate). While this extension delays an official approval/non-approval decision, we think the fact that the extension only concerns REMS – that is, how to mitigate risk after the drug is approved – seems to bode well for ultimate approval of Qnexa. We look forward to hearing the FDA’s decision by July 17 and hope that the agency exceeds expectations and finishes its review faster than anticipated. To read more about Vivus’ Qnexa, please see new now next in diaTribe #40. –VW
We are encouraged to report that the FDA has approved Levemir for use in pregnant women with type 1, type 2, or gestational diabetes. Levemir is a long acting, or “basal” insulin analog made by Novo Nordisk. The FDA approval was based on a study that showed that Levemir is safe to use in pregnant women and does not appear to be associated with a risk of birth abnormalities. Both the study and the decision are important steps forward in helping women manage their diabetes during pregnancy. Strict glycemic control is especially important during pregnancy because abnormal glucose levels increase the risk of miscarriages and complications for the mother as well as birth defects and low birth weight for the infant. Currently, most women without an insulin pump use NPH (intermediate-acting human insulin), which is usually taken twice a day. Since Levemir is a steadier and longer-acting insulin treatment, it is sometimes taken only once a day, though some also take it twice daily. The insulin has also been associated with a smaller risk of hypoglycemia and may provide better glycemic control relative to NPH. We are eager to see how this more convenient and potentially more effective treatment will improve maternity care for US women who get pregnant each year and either have or get diabetes. –NR
We recently had the privilege of attending Medtronic’s 2nd Annual Diabetes Advocate Forum, held at the company’s headquarters in Northridge, CA, on March 30. The event gathered 28 diabetes bloggers and advocates from around the country, including diaTribe advisory board member Jeff Hitchcock (Children with Diabetes), TuDiabetes’ Manny Hernandez, David and Elizabeth Edelman of diabetes daily, Diabetes Mine’s Amy Tenderich, Scott Johnson from Scott’s Diabetes, #DSMA twitter chat founder Cherise Shockley, George Simmons (Ninjabetic), D-Mom Blog's Leighann Calentine, and many others. Some major highlights from the day included:
- An inside look at how Medtronic is developing the artificial pancreas (AP). Lane Desborough, a Medtronic engineer and father of a son with type 1, began with a unique presentation on control algorithm theory as it applies to the artificial pancreas. We then embarked on a tour of the office and got to meet many of the engineers (former rocket scientists!) involved in the development of Medtronic’s AP system. It was particularly fascinating to see “Lane’s Wall,” an impressive collage of posters with overarching design principles, patient data, goals, and timelines. As we understand it, much of this distinctive development approach is borrowed from software and product development at companies like Toyota, General Electric, and Honeywell. Overall, the opportunity to become better acquainted with Medtronic’s team and approach left us inspired and more optimistic about the development of the artificial pancreas. (To read more about recent artificial pancreas developments, see the learning curve in diaTribe #39, the conference pearls in diaTribe #40, and the last chapter of our e-book Targeting a Cure for 1 Diabetes).
- Dr. Francine Kaufman’s inspiring (and heart-wrenching) trips to Haiti. Dr. Kaufman, the Vice President of Global Medical Affairs at Medtronic Diabetes and a renowned pediatric endocrinologist, provided eye-opening stories about treating people with diabetes in Haiti – a country where type 1 diabetes carries an alarming 85% mortality rate at onset. Her candid accounts of seeing patients, educating medical students, and running the country’s first diabetes camp left us moved and incredibly grateful for all that we have access to here in the United States. (For those interested in reading more about Dr. Kaufman’s trips, visit her blog at http://www.reportingonhealth.org/user/1543/blogs.) She concluded her presentation by calling the audience of bloggers and advocates to action. "There is a ton of stuff to advocate for…we might not make it an equal playing field, but let's at least make it a playing field.”
- Our first in-person look at the recently FDA-approved mySentry, a remote monitoring system that enables parents and caregivers to see real-time insulin pump and CGM information from another room (see our detailed coverage of the device in new now next in diaTribe #39). We were most impressed with the monitor’s very loud alarms and sharp, highly readable color screen. Encouragingly, a couple small insurers are beginning to reimburse the $3,000 device (Ohio State Health Plan and AvMed Health Plan in Florida). We hope to see this trend continue, as we believe that a significant number of parents would use the device if they could afford it.
- A talk from Chuck Eichten, author of The Book of Better: Life with Diabetes Can't Be Perfect. Make It Better. Mr. Eichten, a design director at Nike who has had type 1 diabetes for over 30 years, focused on how the combination of creativity and failure ultimately makes us better off. We were thrilled to receive copies of his book, which features an engaging design, humorous drawings, and puts a positive and lighthearted spin on having diabetes. –AB/KC
We last wrote about Type 1 University (T1U) in our test drive in diaTribe #29 – at the time, we were quite impressed after attending two of Gary Scheiner’s advanced online courses for insulin users. The T1U website has now expanded to offer ten classes for those interested in learning more about a variety of topics (e.g., CGM, basal insulin adjustment, weight loss, etc.). However, given the wide breadth of interesting classes and the variance in diabetes education and knowledge, it may not be obvious which class(es) might be useful to take. Encouragingly, Gary and his team are now offering “placement exams” – those interested in one or more of the hour-long courses can take a short five-question test on the course material. To see if you have the knowledge to “test out,” visit http://bit.ly/Hy4Zwv. –AB
In 2011, over 20,000 children (!) in North America attended more than 200 diabetes camping programs. As the 2012 summer camp registration process gears up, we were excited to recently speak with Terry Ackley, the new Executive Director of the Diabetes Education & Camping Association (DECA). Terry reminded us of the excellent resources for families interested in attending a camp or getting more information. The DECA website (www.diabetescamps.org) offers a comprehensive directory of camps, searchable by location (we recommend searching by state rather than distance, as camps are often not located near big cities). The directory also includes camp descriptions and website information, contact details, and session dates. DECA also has a website devoted specifically to parents – you must catch the site’s five-minute YouTube video featuring excited campers, counselors, and DECA staff. –AB