Fighting the nation’s related epidemics of obesity and type 2 diabetes mellitus (T2DM) will take a nationwide strategy that increasingly tailors treatment to individual patient needs. Additionally, new approaches are needed to improve patient adherence and encourage lifestyle changes, which will lead to a healthier population.
That was the consensus of an expert panel convened by The American Journal of Managed Care as part of its conference, “Patient-Centered Diabetes Care: Putting Theory Into Practice,” held April 10-11, 2014, at the Princeton Marriott at Forrestal in New Jersey. Panelists taking part were Jeffrey D. Dunn, PharmD, MBA, senior vice president, VRx Pharmacy Services, LLC, Salt Lake City, UT; Yehuda Handelsman, MD, FACP, FACE, FNLA, medical director and principal investigator, Metabolic Institute of America, Tarzana, CA, and president-elect of the American Association of Clinical Endocrinologists (AACE); Maria Lopes, MD, MS, chief medical officer, AMC Health, New York City, NY; and Kari Uusinarkaus, MD, FAAFP, FNLA, associate medical director, adult primary care and health management, Colorado Springs Health Partners, Woodland Park, CO. Peter Salgo, MD, professor of medicine and anesthesiology at Columbia University and associate director of surgical intensive care, NewYork-Pres-byterian Hospital, served as moderator.
The 90-minute discussion covered the challenges to treatment, including woeful adherence rates to therapies despite recent advances in medication; how to weigh medical therapy against surgical options; and indications for the newest classes of diabetes therapies, the dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 receptor agonists, and sodium glucose cotransporter 2 (SGLT2) inhibitors.
The discussion opened with a snapshot of obesity and diabetes in the United States, where, according to the latest figures reported by the American Diabetes Association (ADA), nearly 26 million people are affected by diabetes, almost all of them with T2DM. Increases in diabetes have closely followed rising rates of obesity by state in recent decades, a point Handelsman noted when he said that California now “is where Mississippi was” years ago. Handelsman said that “turning the tide” on diabetes would require a “nationwide, proactive intervention,” with government health agencies taking a role. The trends are not good, the panelists agreed. Uusinarkaus said that though his home state of Colorado is statistically the nation’s fittest, “Our obesity has finally crept up.…The trends are certainly in the wrong direction.”
The statistics outlined by Salgo are alarming: he quoted an ADA study that shows the economic costs of diabetes are $245 billion a year in the United States, including $176 billion in direct medical cost (28% is for medication).When Salgo asked if therapies alone could do the trick, given the distressing statistics on lifestyle modification, Handelsman insisted that past failures could not be a reason to give up options like better diet and exercise. “We know changing lifestyle works,” he said. The challenge comes when it’s time to pay for intensive, personalized efforts to help patients exercise and make better food choices over the long haul. These interventions are expensive, and not all insurers or employers are willing to include these items in a health plan.
Lopes agreed that prevention has to be part of the solution if the nation is to “bend the cost curve” on treating diabetes and its many complications. Tailoring treatment to individual patients is essential, she said. “We have to figure out what works, and more importantly, what does not work. A lot of this is going to be predicated on data from real-world situations,” Lopes said. The panelists agreed that methods such as using newsletters or mailed reminders to diabetes patients were outdated and simply did not work. Group counseling has produced better results, Lopes said.
New therapies that help patients lose weight, alongside controlling diabetes, offer promise, because the patient can be motivated by seeing progress; studies show that glycated hemoglobin (A1C) levels drop along with excess pounds, even when the amount lost is initially small. Uusinarkaus said the promise of significant weight loss can help motivate a patient, who might refuse an injectable drug for diabetes, to give it a try.
New Agents: The SGLT2 Inhibitors
Salgo led a section of the exchange on the SGLT2 inhibitors, which are the latest tool for clinicians to combat T2DM. The excitement around these drugs comes from their ability to reduce A1C levels and blood pressure, and even aid weight loss, independent of what is happening with insulin and beta cell function.
As Handelsman noted, the basic mechanism of SGLT2 inhibitors has been understood for more than 40 years, but it was only recently that drug development progressed to harness what researchers have known. The kidney has an important role in glucose metabolism. In a patient without T2DM, the kidney reabsorbs glucose and returns it to the body, with SGLT2s accounting for 90% of this process and SGLT1s handling the other 10%. Normally, when the body reabsorbs a certain level of glucose, the rest is discharged in the urine. In T2DM patients, however, this mechanism runs off course, and SGLT2s uptake more glucose than is healthy. The new SGLT2 inhibitors block that process, at least to a point, precipitating more discharge of glucose through
“We know the kidney reabsorbs glucose,” Handelsman said. “When you stop it, you really reduce a lot of exposure to glucose.” He said that in time, this mechanism may be shown to limit some of the more serious longterm effects of T2DM. Salgo noted that the mechanism of SGLT2s upends one of the fundamentals from diabetes care from decades past: letting persons with T2DM “spill sugar.” Tests that measured sugar levels in the urine are no more, and have been replaced with modern blood glucose measurements.
The SGLT2s currently approved by FDA are canagliflozin, which Salgo said starts at a 100-mg dose, and dapagliflozin, which he said starts at 5 mg. Both can be used as monotherapy or in combination with other drugs. As Handelsman explained, while the weight loss effects of these drugs may seem modest (perhaps about 5 pounds), when SGLT2s are added to other therapies that also produce weight loss, the overall effect can be enough to encourage a patient to make lifestyle changes.
Who is a good candidate for SGTL2 inhibitors? Uusinarkaus said that typically, T2DM patients will already be on metformin, but if they remain obese or hypertensive, adding SGLT2 inhibitors may reduce these effects. In his review of the literature, “They do seem to be a little more potent than the DPP-4s.” Due to the way the drugs work in the renal system, however, Uusinarkaus said SGLT2 inhibitors are not recommended for patients who lack good renal function.
Is the weight loss effect beneficial? Lopes said, “Any degree of weight loss is good in these patients, especially since they are obese.” Whether the weight loss is clinically meaningful is measured not only in pounds lost, she said, but also in the way the weight loss affects other comorbidities. When A1C levels and blood pressure readings improve, “That’s quite important to reduction of cardiovascular risks as well.”
View of Payers, Pharmacy Benefit Managers
Dunn said payers and pharmacy benefit managers are open to new approaches and are not unwilling to pay for relatively expensive new therapies if they see signs of progress. Payers and employers balk, he said, when a patient is taking up to 4 drugs and still not achieving control of A1C or blood pressure.
“Every plan out there has thrown everything under the sun at diabetes,” Dunn said. Plans cannot afford to provide intensive monitoring of every person with diabetes, but it does make financial sense to identify those patients most at risk of hospitalization or serious complications, and make highly targeted efforts to guide them to better health.
“We need risk stratification and coordination,” he said. “It has to be done on the right patients.” Dunn also called for shared risk among providers, payers, and the pharmaceutical companies that develop new, expensive treatments. Right now, he said, the risk is all on the payer, and that cannot continue.
Editor’s Note: To view a webcast of the Peer Exchange, visit http://www.ajmc.com/ajmc-tv/peer-exchange.