Will Diabetes Be Taken by Cardiology? Not That, Too!

Richard M Plotzker, MD

Disclosures

April 19, 2019

My fellowship chief, of blessed memory, had a pet peeve.

He was an internationally renowned authority on bone metabolism, president of his professional society during my fellowship, and a man who merged knowledge and insight. But he sometimes viewed endocrinologists as similar to shoppers who would go to a car dealership and put a down payment on the flashiest wheels, only to have them repossessed the next month: They get the car first, but they don't keep it for long.

His view of endocrinology history reflected that sentiment. Endocrinologists pioneered our understanding of the thyroid, only to later compete with nuclear medicine physicians for patients with thyroid pathology.

Adrenal hypertension with or without hypokalemia found its way to the nephrologists only after the endocrinology mavens assessed the chemistry, assays, and algorithms. Hyperlipidemia became the province of the cardiologists and primary care providers, although the understanding of lipid metabolism that enabled the therapy was developed largely by endocrinologists.

My chief, working when DEXA scans were new and bisphosphonates other than etidronate were experimental, correctly predicted that patients with osteoporosis would go to gynecologists and rheumatologists instead of endocrinologists.

We have not yet been usurped in diabetes; however, it may be on the horizon.

Glucose Control Is the Battle, but Longevity Is the War

Although we know that patients with diabetes with better glucose control have better outcomes than those with more severe hyperglycemia, focusing on glucose alone does not fully avert end-organ morbidity. The introduction of statins and renal-protective antihypertensives during the past 30 years has resulted in documented reductions in cardiovascular disease among the diabetic population,[1] even as the prevalence of diabetes has expanded rapidly.

From the other direction, some of the options introduced for glycemic control had untoward cardiovascular effects, including fluid retention from thiazolidinediones and, within that class of drugs, evidence of myocardial infarction and mortality with rosiglitazone.[2]

In 2008, the US Food and Drug Administration mandated, wisely I believe, that all new antihyperglycemic agents had to be assessed for cardiovascular effects during the approval process, and again after a period of common use. This has resulted in several landmark findings of great benefit, albeit with some limitations, to the many people with type 2 diabetes who have already had problems with coronary or congestive failure.

Heart benefits have been identified for the GLP-1 receptor agonists liraglutide[3] and albiglutide,[4] and for the SGLT2 inhibitor empagliflozin.[5] Results from at least one trial of the DPP4-inhibitor linagliptin seemed neutral.[6]

In each of these trials, the glucose-lowering effect of the drug was not very robust, with about a 0.4% reduction in A1c. The various protocols allowed the treating physicians the discretion of continuing nonstudy antihyperglycemics to optimize glycemic control, but these also did not seem to improve A1c levels.

In the 2019 American Diabetes Association Standards of Care, a section was added to review these findings and incorporate these agents with favorable heart outcomes into the treatment sequence, sometimes bypassing less expensive or better tolerated options to attain these heart benefits.

Of note, however, the studies limited their populations to those who already had heart disease. Wretched diabetes control, as in double-digit A1c levels, generally excluded participation. And in the liraglutide trial, the dose was set at the maximum, which may be higher than what is needed for improved glycemic control.

Will Cardiology Cross Into Our Lane?

As these important additional options take their place in diabetes care, it is unclear whether the cardiologists' toolbox will expand. This may have mixed consequences. Cardiology office patients are generally prescreened for existing heart disease, and thus, these physicians may have the option of placing one of these drugs higher on their radar than will my fellow endocrinologists, who tend to look at current metabolic status. Yet, these are not forceful A1c-lowering drugs, and they do have adverse effects.

I can certainly envision getting a couple of phone calls from people whose crotches start to itch after they start getting samples of SGLT2 inhibitors from their cardiologist's cabinet. It may come as a surprise at the next visit to the endocrinologist that the DPP4 inhibitor, which had been quite successful, was stopped by the cardiologist in favor of liraglutide or empagliflozin, or even that liraglutide was added without withdrawing the DPP4 inhibitor, neither of which will correct an A1c of 10.5% as effectively as other therapeutic options.

Blurring the lines of who should be prescribing what, or which lanes physicians of different disciplines should cross, invites some snafus. But data from these studies clearly indicate that these diabetes options have an expanded role for select patients and are probably underused.

So will diabetes go to the cardiologists, just as osteoporosis went to the gynecologists and hyperthyroidism to our nuclear medicine brethren? My fellowship chief seemed almost clairvoyant at times in his predictions.

But they can never take pituitary tumors away from us, at least not the ones the neurosurgeons cannot fully excise.

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