Better drugs, new devices help keep diabetes in check
By Yasmine Iqbal
Gregory O. Clark, MD, assistant professor in the Division of Endocrinology and Metabolism at Baltimore's Johns Hopkins University School of Medicine, calls a college student that he treats for Type 1 diabetes his "superstar" patient. The student recently received a continuous glucose monitoring system, which consists of a pager-sized monitor and a subcutaneous sensor that provides glucose readings every five minutes, as well as a graph showing fluctuations and trends in blood sugar levels.
"This patient had done a great job of managing his food intake and exercise, and his glucose was usually very well controlled," said Dr. Clark, who specializes in Type 1 diabetes. "Recently, however, he'd been developing frequent mild episodes of hypoglycemia and occasional hyperglycemia, especially after a large meal. Now, with the new monitoring system, he can see at a glance where his blood sugar is and where it's headed, and he can treat himself with insulin or food to avoid the highs and lows.
"Seeing motivated patients embrace these new technologies," said Dr. Clark, "is one of the most rewarding parts of my job."
Continuous glucose monitors aren't the only advances creating buzz in the diabetes community. Innovative insulin delivery methods and new medications are making diabetes management more practical and more effective than ever.
New technology and drugs are helping prevent the complications that come along with the disease.
"Physicians and patients will always need to be vigilant in managing diabetes," said John B. Buse, ACP Member, president-elect of the American Diabetes Association. "Now, we now have much better technology and medications for helping them do so and for attacking and preventing the complications that come along with the disease."
The FDA approved the first continuous glucose monitor system, the Medtronic Guardian RT, in July 2005 and it became available in several cities. Other models on the market include the DexCom STS system, available nationally, and the MiniMed Paradigm REAL-Time System, which integrates an insulin pump with a continuous glucose monitor.
Continuous glucose monitors aren't appropriate for all patients. They are expensive (costing up to $5,000 out-of-pocket), they only supplement finger stick values, and they may provide too much data for some patients to understand and digest.
But, noted Dr. Clark, as evidenced by his superstar patient—a tech-savvy engineering major—patients who make the transition to the monitors often can't imagine their lives without them.
"This patient had been doing finger sticks 10 times a day, and he's been able to reduce that to two or three times daily," said Dr. Clark. "Plus, even though he's never had problems with too-low overnight glucose levels, he says that it gives him an added measure of comfort to sleep with the monitor."
Insulin delivery methods
In January 2006, the FDA approved Pfizer's Exubera, a powder form of recombinant human insulin and the first-ever inhaled insulin. Dr. Clark noted that Exubera will probably prove to be most beneficial for patients with Type 2 diabetes because it can't be titrated as precisely as injectable insulin, and patients with Type 1 diabetes often need to adjust to half-unit increments.
The FDA approved the Pfizer Exubera, the first inhaled insulin, in January 2006
Potential downsides are the expense (it can cost up to $5 a day), a cumbersome inhaler, and the need for regular lung function tests (patients with asthma or other breathing conditions or smokers can't take inhaled insulin).
But Dr. Buse noted that for some patients, avoiding needles will outweigh all other considerations. "When you give patients an option of using an insulin pen versus an inhaler, it's remarkable how often they will choose the latter," he said. "I have to admit that I do not understand it. To me the pen seems smaller and more convenient, but it's not me that has to give myself five injections a day."
Stephen G. Rosen, M.D., chief of endocrinology at Pennsylvania Hospital in Philadelphia, added that a more traditional delivery system—the insulin pump—has been improved, as well. "Pumps have gotten smaller, more reliable, and more precise," he said. "They're also much better at helping patients do the math to help them decide on the appropriate insulin dose."
Because inhaled insulin can't be titrated as precisely as injectable insulin, it likely will be most beneficial for patients with Type 2 diabetes.
Other novel insulin delivery methods are in development. Dermal and oral insulin are currently in Phase I studies and buccal insulin is in Phase II studies. These innovations might be key to overcoming one of the biggest problems in Type 2 diabetes management—starting insulin therapy too late.
"Many people are afraid of insulin injections, and physicians often choose to delay insulin therapy or on occasion even use it as a threat to get patients to change their lifestyles," said Sunder Mudaliar, ACP Member, associate clinical professor of medicine at the University of California, San Diego. "But it's really important that patients know that since type 2 diabetes is a progressive disease with progressive decline in insulin secretion, most patients will need insulin at some point in order to achieve optimal glycemic control. By starting insulin earlier, rather than later, they can prevent a lot of the complications that might result if they put it off too long and continue to be in poor glycemic control."
In April 2006, the FDA approved the first in a new class of medications for Type 2 diabetes called incretin mimetics, which mimic the glucose-lowering actions of naturally occurring incretin hormones. Byetta (exenatide) injections stimulate insulin production, inhibit glucagon production, slow the rate of nutrient absorption into the blood stream, and—perhaps most importantly to patients—promote weight loss by increasing satiety.
Exanatide, which is manufactured by Amylin Pharmaceuticals and Eli Lilly and Company, is used with metformin, a sulfonylurea, or a combination of both.
"Byetta can be a dramatically impactful drug for many patients," said Dr. Buse, citing the example of a 65-year-old patient with diabetes who had been on a combination of metformin, pioglitazone, and long-acting insulin. "This patient had always had a hard time controlling his appetite, and he'd been reluctant to start on rapid-acting insulin because he feared he'd gain even more weight.
"After starting Byetta in June, he reduced his metformin and pioglitazone dosages by half and his insulin dose by two-thirds, achieved consistent HbA1C levels of 6, and lost 53 pounds." And, noted Dr. Buse, the nausea that most patients on exanatide experience at first seems to diminish with time.
The newest oral agent is sitagliptin phosphate (Januvia), which was approved in October 2006. It is the first of the DPP-4 inhibitor medications, which enhance active levels of incretin hormones in the body in response to elevated glucose levels. According to Dr. Mudaliar, the effects of Januvia on HbA1C levels aren't as pronounced as exanatide's, but it can be taken orally and doesn't produce nausea, which are clear benefits.
Experts say that the holy grail of an internal artificial pancreas is still years away. However, researchers are close to achieving an external closed-loop system of an insulin pump and continuous glucose monitor in which the pump will automatically administer insulin boluses without the patient's input. Pancreas transplants and islet cell transplantation hold promise, but at this point, the attendant risks of immunosuppressant drugs make this an option for only a few patients, particularly those with severe hypoglycemia or kidney failure.
No matter how far research advances, experts agree that, at least for Type 2 diabetes, the key to better management lies in convincing patients to take charge of their own health.
"About 10% of my patients make dramatic changes in their lifestyles, and when they combine that with medication, their diabetes is completely controlled," said Dr. Buse. While there's a long way to go before the majority of patients start adopting healthy habits, he added, there is plenty of reason for hope.
"Years ago, seeing a diabetes patient come in with a new amputation or a seeing eye dog was almost a weekly event, and now they're few and far between," he said. "That, in itself, is great progress."
Yasmine Iqbal is a freelance writer in the Philadelphia area specializing in healthcare.
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