The year 2016 was eventful in diabetes care and treatment. Breakthroughs in medications and methods of glucose monitoring made headlines.
The American Diabetes Association (ADA) noted that, “An individual diabetes care plan is a core tenet of our Standards of Care and woven throughout the Association’s guidelines. With each health-care device and medication, people with diabetes get access to new options that help them manage their diabetes more effectively, providing opportunities to improve quality of life and health outcomes. 2016 offered a number of key advancements in the tools available to people with diabetes.”
Insulin pump makes dosing decisions
The Food and Drug Administration (FDA) for the first time approved a continuous glucose monitoring (CGM) device that could make medication-dosing decisions automatically using the CGM data. Before, the monitor’s results required confirmation using a fingerstick glucometer before the patient made any insulin decisions.
The Medtronic MiniMed 670G automated insulin delivery pump (AIDP) combines an insulin pump with a sensor measuring a person’s blood glucose level. The device then automatically adjusts basal insulin coverage as needed.
“Some call it a ‘bionic pancreas’; while it isn’t that, the 670G does represent a big leap forward from a regulatory perspective,” said John Buse, MD, PhD, director of the Diabetes Center at the University of North Carolina School of Medicine at Chapel Hill. “This is the first time the FDA has allowed a device to actually administer insulin without human intervention.”
Usually, the pumps deliver insulin appropriate to meals and basal needs. The difference with the new system is that the 670G can independently modify the basal dose during sleep and inactivity. You will still need to make changes in doses around meals and exercise.
Concentrating more on basal insulin
“We always seem to concentrate on bolus delivery and haven’t done enough in stabilizing basal insulin,” said Jane Jeffrie Seley, DNP, CDE, a diabetes nurse practitioner in the Division of Endocrinology, Diabetes and Metabolism at New York-Presbyterian/Weill Cornell Medicine. “I have patients who only change their basal rates one or two times a day over 24 hours. This limits the benefits of insulin pump therapy, so I have to ask why they are even on a pump.”
Upon admittance to an intensive care unit, a patient may be given intravenous insulin continuously and the nurses take hourly blood glucose readings, noted Dr. Seley. Essentially the closed-loop system does the same thing, allowing for continuously changing basal rates at multiple times throughout the day with automatic adjustments based on glucose readings. This should help to stabilize blood sugars, especially while you are sleeping.
AIDP systems may become more important over the next few years. Not only will the next generations be more refined in their decision-making, but they also may be able to add bolus medications to their algorithms. The major limiting factor may be whether bolus medications that act quickly enough can be developed.
“This isn’t a panacea, and it isn’t yet everything we want to be, but it is a big step forward,” said Kieren Mather, MD, associate director for clinical research at the Center for Diabetes and Metabolic Diseases at the Indiana University School of Medicine in Indianapolis. “It is the first of a new wave of treatments that should help those with diabetes.”
Glucose monitoring without fingerstick
Another move forward was the FDA’s approval of the Dexcom G5 CGM system. Like Medtronic’s system, the G5 does not require you to confirm the reading with a blood glucose monitor. (This unit only monitors glucose and cannot make dosing decisions automatically.)
“There are many people using CGMs who don’t use the pumps,” said Dr. Buse. “With the Dexcom sensor, you still have to decide what to do about medications. However, this now eliminates the extra step you previously had to do of checking the reading’s accuracy with a fingerstick.”
From a practical point of view, many people were making decisions on medications without going through the extra step of using a glucometer. With this specific CGM system, the FDA has given the user extra confidence in the reading.
Medicare payments for first time
“Another important outcome from the FDA approval is that Medicare will now pay for CGM use,” said Robert Gabbay, MD, PhD, chief medical officer and senior vice president at the Joslin Diabetes Center. “Many people who had been successfully using these devices had to transition back to fingersticks when they reached Medicare age. This will increase access to CGM and is a clear benefit.”
Now that this initial product has been sanctioned, other manufacturers of CGMs are also seeking approval and could be bringing their products to the market soon. Having more models available should result in lower costs.
For professional use, the Freestyle Libre Pro continuous monitor was recently approved for marketing by the FDA. This glucose sensor is placed on the patient by a health-care professional and is used for 14 days to collect blood glucose data throughout the day and night. There is no need to calibrate the sensor.
At the end of the two weeks, the health-care provider downloads the information and can look at trends and other information to make customized adjustments to medication regimens. A patient version is under review.
“I think the technology will be useful because it is very accurate, comfortable for the patient to wear and easy to apply,” said Dr. Seley. “Meanwhile, for the next 14 days, it is collecting a lot of information so we can better figure out exactly what the patient needs from a medication standpoint and exactly what happens after he or she eats. I think this device could be life-changing.”
Medication lowers heart disease/death risk
There have been advances in medications over the last year. These include new medications, improved delivery systems, and additional indications for older drugs.
“One of the more interesting was the approval of a new label indication for Jardiance [empagliflozin],” said Dr. Mather. “The EMPA-REG study has shown an impact on cardiovascular disease (CVD) rates and lowered heart-related deaths among those with diabetes. This led the FDA to include an indication for this medicine’s use in the prevention of heart disease among people with diabetes who also have risk factors for heart disease.”
The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results — A Long Term Evaluation (LEADER) showed similar findings in those using Victoza (liraglutide). The FDA is still reviewing these results and hasn’t decided if it will allow a similar change in labeling.
Talk to doctor about value of medications
“CVD is the number one killer in diabetes,” said Dr. Gabbay. “The person with Type 2 diabetes and risk factors for heart disease should consider talking to his or her provider about the value of these drugs.”
Those with diabetes have two to four times higher risk for CVD than adults who do not have diabetes. The disease itself is considered a risk factor.
Currently, neither the FDA nor bodies such as the ADA or the American Association of Clinical Endocrinologists offer guidance about whether the cardiovascular benefits alone are a reason to choose among medicines for those with no heart problems or other risk factors. The general consensus of the experts is that at this time, there is no need to change to Jardiance if you are currently well controlled on other medications.
“These heart safety studies were undertaken because the FDA requires all diabetes drugs to have cardiovascular safety studies done after they are released to market,” said Dr. Gabbay. “The researchers were surprised to find that the medications were not only safe for the heart, but actually reduced CVD risk.”
U-500 insulin pen increases safety
The need for very high doses of insulin has lead to the development of U-500 insulin. Until this past year, no insulin pen delivery system had been calibrated for this kind of insulin. People were using U-100 or other syringes to take their medications, resulting in incorrect doses when the conversions were not calculated correctly. The FDA approved a U-500 pen in 2016.
“Some of my patients need hundreds of units a day, which would require as many as eight injections without the concentrated insulin,” said Dr. Mather. “Until this year, we had safety issues because people were drawing up U-500 insulin that was five or more times what the syringe was calibrated for.”
The new administration option eliminates the need to use mismatched insulin and syringe combinations. This lessens the possibility of math or other errors leading to doses that are too high or too low.
Combination medications simplify treatment
Two new combination medications were recently approved for use. Soliqua 100/33 (insulin glargine and lixisenatide injection) and Xultophy 100/3.6 (insulin degludec and liraglutide injection) both combine a basal insulin with a GLP-1 receptor agonist to help control glucose levels after eating or exercise in people with Type 2 diabetes.
As diabetes progresses over time, it can be very hard for patients to transition from pills to several daily injections. Often by this time, they are older and not as independent in their care, making proper basal/bolus insulin treatment more difficult to accomplish.
“By combining the two, you not only get synergies in lowering the needed dose and getting better glucose control, but you also mitigate the side effects of each component,” said Dr. Buse. “The big unanswered question is whether you should use the combination immediately after failing metformin and one of the component parts or wait until both haven’t worked as separate medications. The trials to answer that are ongoing.”
These medications are a combination of simplicity and efficacy. However, for an individual, the simplicity of a single shot daily may be the more important advancement.
After a certain amount of time, a pill becomes generic and other makers are able to produce their own versions, which often results in reduced costs to users. For injectable hormone medications, there is a different process that results in what the FDA will call a “biosimilar” drug that acts in basically the same way as the older medication.
The FDA approved the first biosimilar in the diabetes space in 2016. Basaglar (insulin glargine injection) is essentially the same as Lantus (glargine). While the early clinical results are good, the price changes have been disappointing.
“Biosimilars could have been big, but haven’t turned out that way,” said Dr. Gabbay. “The idea was that biosimilars being available would lead to lower prices like generics do for other medications. So far we haven’t seen that, although this journey is just beginning.”
Overall, 2016 was a year of many firsts in several areas of diabetes. Some, such the AIDP systems, are in their infancy. Others are finding new indications for older medications, including Jardiance. The future of diabetes treatment will sort out which advances are important and which aren’t as we acquire more understanding of how they fit with patient needs and how well they work in the wider diabetes population.