Endocrine Today 20th Anniversary

Endocrine Today 20th Anniversary

Issue: January 2022
Disclosures: Anhalt is vice president and global head of medical and clinical affairs, diabetes care, for BD. Eckel reports receiving remuneration from Amarin, Novo Nordisk and WW for advisory board participation. Einhorn reports no relevant financial disclosures. Gavin reports receiving consulting fees from Abbott, Medtronic and Novo Nordisk. Grunberger reports receiving speaking or research fees from Abbott, Eli Lilly and Novo Nordisk. Peters reports participating on advisory boards for Abbott Diabetes Care, AstraZeneca, Eli Lilly, Medscape, Novo Nordisk and Zealand; receiving research support from Dexcom, Insulet and donated devices from Abbott Diabetes Care; and holding stock options with Omada Health and Teladoc. Rodbard reports relationships with Bayer, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk, Sanofi and Zealand.
January 26, 2022
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Technology, unexpected study findings redefine diabetes management over 20 years

Issue: January 2022
Disclosures: Anhalt is vice president and global head of medical and clinical affairs, diabetes care, for BD. Eckel reports receiving remuneration from Amarin, Novo Nordisk and WW for advisory board participation. Einhorn reports no relevant financial disclosures. Gavin reports receiving consulting fees from Abbott, Medtronic and Novo Nordisk. Grunberger reports receiving speaking or research fees from Abbott, Eli Lilly and Novo Nordisk. Peters reports participating on advisory boards for Abbott Diabetes Care, AstraZeneca, Eli Lilly, Medscape, Novo Nordisk and Zealand; receiving research support from Dexcom, Insulet and donated devices from Abbott Diabetes Care; and holding stock options with Omada Health and Teladoc. Rodbard reports relationships with Bayer, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk, Sanofi and Zealand.
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This year marks the 20th anniversary of Endocrine Today. In the 2 decades since Endocrine Today was launched, the field of diabetes has undergone immense change.

Clinical developments and studies have catalyzed changes in the way health care providers think about the goals of diabetes care and what the approaches and tools for managing the disease should be, according to Healio | Endocrine Today Co-editor James R. Gavin III, MD, PhD, clinical professor of medicine at Emory University and chief medical officer of Healing Our Village.

“For somebody who’s been in this space for 50 years, the last 20 years have been unbelievable in terms of the pace of change, the impact of that change and what is now possible with respect to changing outcomes in diabetes writ large,” Gavin told Endocrine Today.

James R. Gavin III

Diabetes management has moved from finger sticks and insulin injections to revolutionary devices for monitoring blood glucose and delivering a selection of insulin products. New medication classes help people with type 2 diabetes maintain lower glucose levels without risking hypoglycemia, and safety studies of these drugs revealed physiologic connections that now recommend their use for treating diabetes comorbidities, including obesity and cardiovascular and renal diseases.

“We are living in exciting times around continuous glucose monitoring. There are more opportunities to provide solutions that work — miniaturizing devices, customizing them, marrying them to insight tools in a holistic way,” Henry Anhalt, DO, a pediatric endocrinologist and vice president and global head of medical and clinical affairs for BD Diabetes Care, told Endocrine Today. “But this is one part of a three-legged stool: We talk about biology, drugs and technology. All three of those play such an important role in diabetes care.”

Technology allows patients to ‘own their disease’

The first CGM was approved for professional use in 1998 and did not provide real-time data. Finger sticks were the best way to assess blood glucose on the spot. The somewhat painful and cumbersome process of jabbing and recording meant many people avoided performing finger sticks often or at all, according to Anne L. Peters, MD, professor of clinical medicine at Keck School of Medicine of the University of Southern California and an Endocrine Today Editorial Board Member.

Anne L. Peters

Today, finger sticks are still often necessary, but many glucose meters have eliminated the logbook and can record and share data via a smartphone app. Most people using insulin still perform multiple daily injections, typically with a pen device, but a “smart” insulin pen can now track data and recommend doses.

“CGM is important, but you must remember, only about 1 in 10 today have access to CGM, either because it is not covered, their practitioner doesn’t use it, or they do not want it,” Daniel Einhorn, MD, FACE, FACP, a clinical endocrinologist with Diabetes and Endocrine Associates and medical director of Scripps Whittier Diabetes Institute in La Jolla, California, told Endocrine Today.

“CGM tells a story, rather than a list of facts [as with a logbook]. Patients finally see the story of their diabetes that they never saw before,” said Einhorn, who is also an Endocrine Today Editorial Board Member. “Structured blood glucose monitoring — ‘BGM’ — which means getting enough BGM readings to create a true profile of glucose, is like a CGM. The American Diabetes Association has recommended this. Devices and strategies that make more BGM easier and which create the glucose profile are critical.”

CGM for consumer use became available in the U.S. in 2001 with a wrist-worn, noninvasive sensor, which was discontinued in 2007. More contemporary CGM devices became available beginning in 2004 with the Guardian REAL-Time CGM system from Medtronic and then with systems from Abbott and Dexcom. Medtronic introduced an integrated sensor and insulin pump in 2006.

Since then, CGM sensors have become smaller, more accurate and longer-wearing with data and trend reports instantly available via smartphone apps. Insulin delivery systems, too, have become “smarter” with advanced decision-support tools using artificial intelligence technology. And the two types of devices have come together in automated insulin delivery systems or “artificial pancreas.”

“[Twenty years ago,] we didn’t have the ability to easily see 24/7 glucose profiles, and so adjustments to insulin were not nearly as fine-tuned. [People using insulin] would have a lot more hypoglycemia,” Peters said. “There was a lot of guessing — the trend arrows that you see on CGM don’t happen with finger sticks. [Now,] my ability to help people avoid lows is much greater, and it’s been easier to, for instance, adjust the basal insulin. I have such a better handle on the profile.”

George Grunberger

George Grunberger, MD, FACP, MACE, chairman of the Grunberger Diabetes Institute in Bloomfield Hills, Michigan, said he uses professional CGM for every new patient.

CGM allows people with diabetes to “own the disease,” Grunberger said.

“For me to walk into an exam room now, sit down, and the patient tells me what they already did because of what they saw — now they own the disease,” he said. “The CGM totally revolutionized not only my life as a practitioner, but the patients’ lives too.”

Drug trials yield new understanding of diabetes ‘control’

CGM and other diabetes technology have so far been adopted by people with type 1 diabetes and those with type 2 diabetes who require insulin. For others with type 2 diabetes, new drug classes developed during the past 20 years — including DPP-IV inhibitors, GLP-1 receptor agonists and SGLT2 inhibitors — have enhanced patient safety, and some have reduced risks presented by comorbidities.

Physicians have long recognized the strong correlation between diabetes and cardiovascular disease, but research over the past 20 years cemented the relationships not only between diabetes and CVD, but also renal disease and obesity.

“Changes in our thinking about differences in the paradigm of diabetes management actually start with things like STENO-2 [published in 2003], a study that said it’s not just important to target glucose, but you’ve got to target these other risk factors. Why? Because that’s what’s necessary to prevent the vascular outcomes that we worry about,” Gavin said.

STENO-2 showed that targeting such things as blood pressure, lipids and albuminuria along with glucose could reduce risks for CV and microvascular events.

Complicating the changing paradigm, however, was a fear that glucose-lowering drugs might increase risks for CV mortality, myocardial infarction and stroke. A 2007 meta-analysis of clinical trial data noted an increased rate of MI with rosiglitazone. This finding prompted the FDA in 2008 to require that all new diabetes drug trials investigate CV risk. These CV outcome trials (CVOTs) not only cleared rosiglitazone, but also showed unexpected CV and renal benefits along with weight reduction.

“Any new drug coming to the market for diabetes had to show CV safety — not superiority,” Helena W. Rodbard, MD, FACP, MACE, medical director at Endocrine and Metabolic Consultants in Rockville, Maryland, told Endocrine Today. “Back in 2008, at the onset of the CVOTs, no one would have anticipated that so much would be learned so quickly. These studies added immensely to our understanding of not just diabetes, but cardiovascular disease.”

Henry Anhalt

Subsequent CVOTs demonstrated dramatic benefits from several medications from several classes with respect to heart failure and renal disease, even for people without diabetes, Rodbard said.

The CVOTs changed practice as well as understanding, according to Gavin.

“[These studies] demonstrated the kind of impact that actually shifted the paradigm of what ‘control’ really means,” Gavin said. “We no longer think of type 2 diabetes as being controlled just because you reach an HbA1c target. That’s now become just one of the stops along the way. Controlling this disease really means you have gotten your arms around those risk factors and other pathophysiologic processes that drive cardiovascular outcomes.”

Robert H. Eckel

The experience of the CVOTs, together with thinking about metabolic syndrome, has led to an expanded understanding of how diabetes merges with CVD through insulin resistance and obesity in cardiometabolic diseases, according to Robert H. Eckel, MD, emeritus professor of medicine in the divisions of cardiology and endocrinology, diabetes and metabolism, former professor of physiology and biophysics, and Charles A. Boettcher II Chair in Atherosclerosis at the University of Colorado Anschutz Medical Campus.

“There is a domino effect that transitions simple obesity to outcomes that relate to heart attack and stroke and death from cardiovascular disease,” Eckel, who is also a past president of ADA, the American Heart Association and the Obesity Society, told Endocrine Today.

“Over 20 years ... ‘cardiometabolic disease’ has become an accepted term in this interface between diabetes, obesity, metabolic syndrome and cardiovascular disease. That, in my opinion, is the largest advance,” Eckel said.

Rodbard attested to the expanded understanding of the place of diabetes in medicine.

“There has been a much closer relationship among specialties [since the CVOTs],” she said. “Now, endocrinologists, cardiologists, nephrologists, primary care physicians, we all interact closely and learn from each other. All that is good.”

Guidelines move to precision medicine

Until recently, type 2 diabetes management guidelines from the ADA and the American Association of Clinical Endocrinology began with lifestyle changes and a metformin prescription followed by newer agents in succession over time.

“Most everyone was trained on the idea that you start with lifestyle, and then there are a series of steps before you get to the latest drugs. To turn that on its head is still taking a little bit of time,” Einhorn said. “[Eventually, guidelines] will change to say regardless of who you are, you get both agents — an SGLT2 inhibitor and a GLP-1 receptor agonist — and lifestyle, and at least a little CGM to see that you are accomplishing what you can. Then you’ve got the package.”

The ADA’s 2022 Standards of Medical Care in Diabetes is a step closer to Einhorn’s prediction. It calls for individualizing therapy for adults with type 2 diabetes by choosing a first-line therapy based on the patient’s comorbidities and factors such as cost, access and management needs. The guideline also states that all people on multiple daily insulin injections or an insulin pump should be offered CGM and those on basal insulin alone can be monitored with a CGM. In addition, automated insulin delivery systems are the preferred method for the treatment of type 1 diabetes, but the choice of treatment modality should always be based on patient circumstances and preferences.

“The guidelines for the very first time are making specific recommendations based on the pathophysiology and based on clinical characteristics of patients that are not ambiguous, and that’s a real sea change in diabetes management,” Gavin said.

The concept of “precision diabetes” has developed over the past decade in response to knowledge gleaned from CGM and CVOT data, Eckel said.

“How can I identify patients who we can personalize treatment for, in terms of lifestyle and therapeutic interventions that may be beneficial? That’s not only true for treatment of the glycemia in relation diabetes, but also related conditions like blood pressure, lipids and other considerations that relate to cardiovascular disease complications,” Eckel said. “The American Heart Association and the American College Cardiology and many other related professional organizations have signed on to guidelines that now include the benefit of SGLT2 inhibitors and GLP-1 receptor agonists in the treatment of patients with diabetes or who are at high risk for complications of cardiovascular disease and renal disease.”

Bright future, but challenges remain

“For people who can access the technology and the meds, this is the best time ever to have diabetes because you can live as if you do not have diabetes,” Einhorn said. “Even frequent blood glucose monitoring may not be so necessary now with these new agents. You can take your medicine once a day or even once a week, leave your house and live life like anybody else, and expect to live a long healthy life.”

What has not improved in the diabetes setting is related to social issues — more children are now presenting with type 2 diabetes, prices for newer medications and insulin are unaffordable for many, even with biosimilar insulins on the market, and a shortage of endocrinologists and diabetes experts mean most people with diabetes never see a specialist [see Endocrinologists propose diabetes fellowship programs to address growing gap in care].

Peters said she finds diabetes technology “both wonderful and constraining at the same time” with too much paperwork and data overload for office staffers.

However, at least in terms of the science, further breakthroughs in diabetes care are perhaps on the way.

“What will happen in the next 20 years? I would say the sky is the limit,” Rodbard said. “I would predict we may see a cure, especially for people with type 1 diabetes, with stem cell research and other things we can’t even fathom. If we can even delay it, we delay complications and improve quality of life for kids and their families. The future is very bright.”