The Los Angeles gathering of the Institute for Value-Based Medicine focused on the need to intervene early in the course of diabetes, so that patients can avoid long-term complications. Over the past decade, cardiovascular outcomes trials for glucose-lowering therapies have revealed unexpected benefits, offering new opportunities for cardiologists.
To show why diabetes has become a public health crisis, Peter Butler, MD, the renowned endocrinologist from the University of California at Los Angeles (UCLA), tells the story with pictures: The food portions are bigger. The amount of time spent in front of screens last longer. The distances we commute are farther. Too much eating and sitting do not add up to good health, he explained, creating a $327 billion tab for diabetes just in the United States.1
What’s worse, Butler said, “We’ve exported our lifestyle,” making diabetes, driven by rising obesity rates, a growing global threat. In 2018, the journal Diabetes estimated there are 500 million cases of type 2 diabetes (T2D) worldwide, and rates are comparable between wealthy and poor countries.2 “Clearly, we have to take care of people and manage it,” he said.
To understand the challenges that health systems face—and what must be done do to meet them—Butler, the division chief of endocrinology and director of the Larry Hillblom Islet Research Center at UCLA, hosted the April 17, 2019, session of the Institute for Value-Based Medicine®, “Diabetes Management: Advances in Treatment and Management to Reduce Cost and Improve Outcomes.” The session, presented by The American Journal of Managed Care®, explored how investing in better interventions—from newer therapies to improved monitoring to more attention to the whole person—leads to better health and saves money in the long run.
An all-star lineup joined Butler at the Loews Santa Monica Hotel: Anne L. Peters, MD, professor of medicine at the Keck School of Medicine at the University of Southern California (USC) and director of the USC Clinical Diabetes Programs; Karol E. Watson, MD, PhD, FACC, director of the UCLA Barbra Streisand Women’s Heart Health Program, codirector of the UCLA Program in Preventive Cardiology, and director of the UCLA Cardiology Fellowship; and Sachin H. Jain, MD, MBA, president and chief executive officer for CareMore Health.
Getting Empagliflozin on Formulary: A Case for Cost-Effectiveness
Peters is not a typical diabetes expert. Besides being involved in cutting-edge research in both drug and device development, she splits her time between patients on both the west side of Los Angeles County, where most patients have health coverage, and the east side, where she said, “there are some of the saddest stories you’ve ever seen.”
Her service on the county’s Department of Health Services formulary committee offera a front-row seat for debates about price and value. “One of the things I know the most about is cost,” Peters said. She’s had to make the case that certain therapies that may have higher acquisition costs ultimately save money by preventing complications that occur when diabetes is not well controlled.
She is not a fan of insulin or sulfonylureas, but she recognizes that both will stay on formulary in T2D for now. But Peters succeeded in getting empagliflozin on the Los Angeles County formulary 2 years before the EMPA-REG OUTCOME trial results were reported.3 She told the IVBM attendees how she convinced the committee that the sodium glucose cotransporter 2 (SGLT2) inhibitor was keeping patients out of the hospital for heart failure—a result that has been borne out across the class in multiple studies.4-6
With empagliflozin, she said, “You get an immediate benefit.” For low-income patients especially, that makes a difference. “Heart failure is so hard for these patients. It’s heartbreaking. They don’t have the home environments where they can deal with sodium and everything else that would really make their lives better.”
Overall, avoidable complications persist in diabetes. Peters said only 14.3% of adults with diabetes reach all of their targets—not just glycated hemoglobin (A1C), but also blood pressure (BP) and cholesterol,7 and there are serious knowledge gaps among primary care physicians. “I’ve asked some of my best internist friends, ‘What do you do after metformin?’ And most of them look at me blankly. That is not a good start. We’ve made the algorithm too complicated.”
Diabetes causes suffering, Peters said, such as blindness, kidney failure, amputations, and tooth loss. “There’s an increased risk of depression and a whole host of other things,” she said. “Diabetes is not your friend, but my feeling is, if you take care of it well, none of this stuff has to happen. It’s the taking care of it well that matters, and that means access to healthcare, which I think is the most important part of all of this.”
As patients get T2D at younger ages,8 it’s essential to achieve and maintain glycemic control. “A 45-year-old who gets diabetes is someone who is going to live long enough to get complications,” she said. This is what costs the health system money. Patients classified as obese, in particular, incur high costs from joint replacements and sleep apnea. “But more than that, their lived experience is miserable.”
Even when patients get outstanding care, they remain at high risk for heart attacks. “Every time I hear a patient of mine [died suddenly], I race back to their chart to make sure I didn’t miss something,” Peters said. “One of the reasons I’m so passionate about this is that most of my patients are really well risk-modified, and they still die. “I know we’re all going to die,” Peters said. “But I’d prefer it not be in your 50s and 60s.”
Which New Therapy Makes Sense in Type 2 Diabetes?
Metformin remains the first therapy patients take when T2D is diagnosed. Now that SGLT2 inhibitors have been shown to have cardiovascular benefits, Peters said, there’s an argument to be made that they should be foundational for patients with T2D with comorbid cardiovascular disease. The question becomes: Which of the newer T2D therapies should come next? First Peters, and then Watson, reviewed evidence from a key set of studies—the cardiovascular outcomes trials (CVOTs)—that have fundamentally changed treatment of T2D and brought cardiologists into the mix in the treatment of this condition.
As Watson later explained, in 2008, the FDA began requiring CVOTs to show that new glucose-lowering therapies at least did not cause harm—meaning
they did not cause heart attacks, strokes, or other events—to patients with T2D.9 Watson shared how the 2015 announcement of the EMPA-REG OUTCOME results3—that the SGLT2 inhibitor had reduced hospitalization for heart failure by 35% and all-cause mortality by 32%—hit like a thunderclap. That set off the wave of rethinking among both endocrinologists and cardiologists that culminated with the American College of Cardiologists’ (ACC) 2018 Expert Consensus Decision Pathway on Novel Therapies for Cardiovascular Risk Reduction in Patients With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease.10
CVOTs for 2 classes of therapy—SGLT2 inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists—have shown results with cardiovascular benefits. Peters reviewed the results and the criteria physicians should consider in deciding which class makes sense for a patient:
A1C Is No Longer the Measurement That Matters
Peters concluded with a discussion about moving away from A1C as the holy grail of measuring glycemic control. Use of continuous glucose monitoring (CGM) systems has highlighted the importance of time in range—which tells patients and physicians what percentage of time a person’s blood glucose stays out of hypo- or hyperglycemia, or between 70-180 mg/dL. Time in range, she said, is a much better indicator of a person’s likelihood of developing microsvascular and macrovascular
complications. With the availability of factory-calibrated systems, such as Dexcom’s G6 and Abbott’s Freestyle Libre, or the Eversense implant that requires no day-to-day involvement from the patient, a more complete picture emerges of the importance of maintaining glycemic control.
“The thing we know from these devices is that probably the A1C is a useless number,” Peters said. The next step is moving toward consistency in CGM reports, more like those that come from an electrocardiogram. Use of CGM allows physicians to demonstrate to insurers that even if a patient’s A1C seems normal, if time in range is volatile, a person with diabetes needs the glycemic control that an SGLT2 inhibitor provides to avoid long-term complications.
Peters expects that re-examining data from landmark studies like the Diabetes Complications and Control Trial will show the link between time in range and retinopathy or nephropathy. Thus, using CGM “will help us find the patients who need more or less help.”
“But it’s going to take a lot of teaching to get people to understand CGM,” she said.
For Cardiologists, “This Is Your Lane”
For years, Watson explained, the success that cardiologists saw in managing lipids and high blood pressure—due in large part to improved therapies—wasn’t repeated when it came to diabetes. “Peter and I and Anne and I have patients in common, who, despite perfect lipids and blood pressure, were still having events, which is heartbreaking,” she said.
“We know cardiovascular disease is the leading cause of death and morbidity for patients with diabetes, and it costs a lot of money,” Watson said. “And we know that it comes with a lot of co-existing risk factors like hypertension or dyslipidemia, but it doesn’t matter…I can get their lipids perfect, I can get their blood pressure perfect, and diabetes itself is going to confer increased risk.”
But getting cardiologists involved in diabetes care, to encourage them to target this risk with antihyperglycemic agents, represents a change in thinking. And this was the point of ACC’s Expert Consensus Pathway document. “It’s one of the most revolutionary documents that ACC has ever released,” she said. “We’re trying to get cardiologists to understand: This is your lane.”
Watson said the document has 3 essential points: (1) Cardiologists should screen for T2D, (2) they should treat the risk factors, and (3) they should treat with antihyperglycemic agents, specifically SGLT2 inhibitors and GLP-1 receptor agonists. “We understood that when we put out this document, cardiologists would need a lot of hand-holding.”
The document further identified empagliflozin as the preferred SGLT2 inhibitor, and liraglutide as the preferred GLP-1 receptor agonist; as Peters did, Watson identified SGLT2 inhibitors as the preferred class for those at risk of heart failure. If patients have osteoporosis, are overweight, or are at risk for amputation, GLP-1 receptor agonists may be the better choice.
SGLT2 inhibitors, Watson noted, compare favorably in treating heart failure to many drugs developed specifically to target this condition; several trials are studying this class in heart failure for patients with and without diabetes. The first studies will report findings in 2020.11-15 “I’m putting my money on the agents,” she said.
Evidence Propels Change in Thinking
Prescribing antihyperglycemic agents is just one area where cardiologists have shifted their thinking in light of new evidence, Watson said. Besides ACC’s Expert Consensus Pathway, updated primary prevention guidelines16 reflect recent findings:
Aspirin. Watson said the ASCEND trial results, which showed that taking aspirin for primary prevention reduced vascular events but was offset 1:1 by bleeding risk, was “the nail in the coffin” for giving aspirin to older adults who do not have coronary heart disease.17 Under the new primary prevention guideline, ACC has sharply curtailed who is recommended to receive daily aspirin.
Hypertension. New guidelines adopted in 2017 by ACC and the American Heart Association redefined what constitutes high BP and lowered the threshold for treatment, based on the SPRINT study results.18,19 BP ≤120/80 mm Hg or below is considered normal. Systolic BP >120 and ≤130 mm Hg is elevated; stage 1 high BP is defined as systolic BP >130 and ≤139 mm Hg or diastolic BP >80 and ≤89 mm Hg. Stage 2 high BP is defined as systolic BP <140 mm Hg or diastolic BP <90 mm Hg.
Cholesterol. Watson was an author on the 2013 guidelines that identified 4 groups that need statins: (1) patients who have had an event, (2) patients with low-density lipoprotein (LDL) cholesterol above 190 mg/dL, (3) patients with diabetes, and (4) very-high-risk primary prevention patients, based on age and other factors.
The idea of cardiologists screening for diabetes and treating risk factors is new, but necessary, Watson said. “If we don’t do something to improve outcomes in patients with diabetes, they’re going to keep having events, and that’s why cardiologists are going to become diabetologists.”
Organizing Healthcare Delivery Around the Whole Patient
So, if every patient just gets the right medication, we can solve this problem called diabetes, right? If only.
CareMore’s Jain reminded the providers gathered at the session of a disturbing fact: “We are developing 21st century medicine with a 19th century delivery model,” he said. The idea that closing the gaps in healthcare is as simple as making patients better consumers might make sense to economists and people who don’t practice medicine, Jain said. Then he shared an anecdote that illustrated how the solutions being developed for consumers don’t always match the needs—or desires—of the people who use the most healthcare.
Early in his career, Jain served in the Office of the National Coordinator (ONC) for Health Information Technology. So, when he was home visiting his family recently, his mother asked him to put that experience to use and set up all her patient portals with her doctors. The bell went off that so much money and time has been expended on something that has very little value for his mother. “There is the false idea that people want to use this stuff,” he said, that patients are going to order healthcare the way they order things on Amazon.
Patients with chronic disease, the kind of patients that CareMore sees, are likely not using this type of technology in a meaningful way. The health system held a town hall with them at a hotel and listened to what the patients had to say.
“Healthcare should anticipate and deliver on people’s needs,” he said. Instead of giving them choices they don’t understand, healthcare should understand that expertise matters and that the cheapest solution may not be the best one. The idea that poor people need “skin in the game” to responsibly use healthcare is also out of touch. “People should not pay out of pocket for the things they need,” he said. “We should not have co-pays for the things that people need to live,” such as insulin.
If health systems want to keep patients from returning to the hospital, then things like using Lyft to get them home, ensuring there’s a healthy meal waiting for them when they arrive, making sure they have social contacts, and confirming that they see the same doctor for follow-up care all matter.
CareMore has pioneered services like toenail clippings because they offer regular touch points with the healthcare system, Jain said. When the average daily cost of a hospital bed in Los Angeles County is $3500 to $4000, he said, “You can buy a lot of prevention” by focusing on cost avoidance.
CareMore integrates dental coverage and uses a patient’s time in the chair to check on other vital signs. Its Togetherness Program touches at-risk seniors who either live alone or need support to adhere to medications or get engaged in community or fitness programs.
How does CareMore do it? The fully integrated care and delivery system for Medicare and Medicaid patients is fully at risk, because as Jain puts it, CareMore’s way of doing things would not be possible in “our broken fee-for-service delivery system.”
“We believe risk is freedom,” he said.
So, when Butler asked how to explain why the field of diabetes has better drugs than ever, but the average A1C is not better than it was 10 years ago, Jain said the need to reinvent the delivery system is the issue.
“A lot of the talk in health policy is around delivery science,” he said. “A lot of what we need is more common sense. Radical common sense.”
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