Aus Alzaid, MD

Disclosures

July 09, 2015

It was obvious to anyone attending this year's annual American Diabetes Association (ADA) meeting in Boston that the rising cost of diabetes medications was high on the agenda of the conference organizers. The notion that insulin therapy is becoming unaffordable in the United States has raised real concerns within the diabetes community.

Aus Alzaid, MD

The price of insulin has apparently gone out of control over the past decade: The cumulative inflation rate has increased by 20%, whereas the price of several insulins has increased by a staggering 300%-500%. Even insured patients are now feeling the pinch, through higher copays demanded before they can receive the medication.

Unfortunately, no clear strategy is in place to regulate the price of insulin and rein in the costs. The "buck" has been passed down the line to the healthcare provider to manage costs and decide which insulin to prescribe and which one to ration. The treating physician has to contend with being responsible for not only the patient's health, but also his or her wallet.

Deciding whether a given treatment provides value for money, however, is subject to a physician's personal sentiment as much as to his or her clinical judgment. As individuals, physicians may view the value of money in different ways. Moreover, some of us are quickly dazzled by glitter, advertising, and the subtleties of the various pharmaceutical companies.

At the annual meeting, the ADA stepped into the controversy with a debate[1] to provide a rational basis for making decisions on behalf of our patients with diabetes. Because of the high cost of the new insulins and the fact that the majority of patients taking insulin have type 2 diabetes (T2DM), the debate was restricted to evidence relevant to this population only.

The question put forward was, are the new insulins worthwhile in the management of T2DM?[1] Two veteran diabetes experts with contrasting personal styles but matching academic status and clinical expertise argued the case for and against the place of new insulins in diabetes practice. Dr Richard Bergenstal, executive director of the International Diabetes Center in Minneapolis, Minnesota, debated in support of the costly new insulins; Dr David Nathan, director of the General Clinical Research Center and of the Diabetes Center at Massachusetts General Hospital in Boston, Massachusetts, argued against them.

Dr Bergenstal: New Insulins Are Worth It; Let's Not Stop the Tide of Innovation

Dr Bergenstal opened the debate by reminding everyone that only 30% of patients with T2DM on insulin reach their glycemic target level and that this disappointing figure has stayed the same for decades. The arrival of the new insulins may bring about a change in the diabetes scene and improve the management of T2DM. Given their superior kinetic properties, the new basal insulins (such as degludec, concentrated glargine, and peglispro) offer a longer, smoother, and much more predictable glucose response than the current basal insulins.

Bergenstal urged that we should embrace such novel insulin technologies and adopt a "trust but verify" approach to new insulins: Trust the unique properties that they offer, and later verify their wider clinical benefits with surveillance studies in the real world.

The other clinical advantage that Bergenstal emphasized was the low risk for nocturnal hypoglycemia associated with insulin analogues. The clinical and scientific evidence regarding this is overwhelming. Severe hypoglycemia is a serious and ugly complication of insulin therapy and is very much feared by patients and their families. Bergenstal estimated the annual cost of hospital admissions due to hypoglycemia in people with T2DM to be around $4 billion, implying that some of this cost could be avoided if we used insulin analogues.

Bergenstal insisted that the patient's experience should always be taken into account. Issues important to patients should also be important to healthcare providers. He further suggested that the patient's quality of life should be assigned its own price tag when the cost of insulin is being considered. Convenience, flexibility of injection timing, avoidance of weight gain, and minimal disruption of daily routines are issues that genuinely matter to patients—and by using the new insulins, these matters can be readily addressed.

Bergenstal concluded his presentation by calling for the development of a better way to quantify the cost of diabetes management that includes hypoglycemia management and quality-of-life measures. He urged the introduction of effective markers of dysglycemia and encouraged the use of continuous glucose monitoring to detect "invisible" glycemic risks and benefits that go beyond the patient's symptoms or the bare A1c values.

Bergenstal conceded that if this current trend in cost continues, we should try to reserve expensive insulins for patients who need them the most. If such an approach becomes a desirable clinical option, he said, then we should establish clinical guidelines to identify such patients.

Dr Nathan: New Insulins Are Not Worth it; They Only Exemplify the Power of Advertising Over Substance

Dr Nathan began his argument by pointing out that the reduction in mortality and diabetes complications seen in studies[2,3,4] conducted in patients with type 1 diabetes mellitus (T1DM) and those with T2DM was achieved with the standard, old-fashioned insulins, such as neutral protamine Hagedorn (NPH), ultralente, and regular insulin. By contrast, insulin analogues have yet to prove their value in relation to clinical outcome (the ORIGIN Trial[5] being an inadvertent omission).

Nathan suggested that we should draw clear distinctions between clinical experiences observed in patients with T1DM vs those with T2DM. He gave two clinical examples to highlight this point.

First, severe hypoglycemia, a common and serious complication of insulin therapy in patients with T1DM, is rare in patients with T2DM. Data presented showed the frequency of nocturnal hypoglycemia to be 20 times lower in T2DM than in T1DM when patients were matched for similar A1c level.[1]

Second, prandial insulin analogues, although a welcome addition to the care of patients with T1DM, are clinically less important in the treatment T2DM because "Insulin therapy relies mostly on basal insulin administration in T2DM," Nathan said.

Nathan presented data showing similar glycemic effects between old and new basal insulins in patients with T2DM. The differences in A1c levels observed were small (< 0.1%) and therefore of doubtful clinical significance. Furthermore, the rate of severe hypoglycemia found in studies was exceedingly low and did not warrant concern. If the rate of hypoglycemia was higher during the day with one insulin regimen, it was higher at night with the other.

Nathan then asked: Why should the patient with T2DM pay nearly three times the price for insulin glargine if NPH insulin is just as effective and the risk for severe hypoglycemia is rare, no matter which basal insulin is used? One could almost hear Nathan implying that the issue of nocturnal hypoglycemia has been deliberately manipulated to instigate fear and promote certain insulin products.

Nathan remarked on the recently approved inhaled insulin powder. He argued that no matter how you look at the evidence, whether it was studies in patients with T1DM or T2DM, inhaled insulin performed no better and may have been slightly (albeit not significantly) worse than the standard insulin injection regimen. Inhaled insulin powder is "just more expensive" than the regular insulin regimen, he repeated.

Nathan then referred to the New England Comparative Effectiveness Public Advisory Council, which relies on a combination of clinical, scientific, and economic factors to determine the true value of medications used to treat diseases. It recently concluded that NPH insulin is just as effective in lowering blood glucose as newer insulin analogs while costing only one third as much.[6] The group says that about 80% of patients with type 2 diabetes who take insulin rely on insulin analogs, suggesting that NPH may represent a significant cost-savings opportunity.

This Observer's Thoughts

My initial impression was that both speakers were there to present their own views on the subject, but I later learned that the speakers were randomly assigned which side of the argument to take by the ADA. Thus, I must congratulate both speakers on making such passionate and convincing presentations, regardless of their personal convictions. The debate was outstanding, and at times, it looked as if it were a dispute between a physician worried about issues of today and another who saw the clear promise of tomorrow.

Bergenstal made some excellent points, including his reminder that the patient's quality of life should not be overlooked. If you are a person with diabetes, a good quality of life is priceless. He also argued in favor of technology and innovation as the way to advance diabetes care in the future—a belief dearly held by most of us. However, I found that the rest of Bergenstal's argument sounded much better on paper than if applied to clinical practice.

I was swayed by the practical points raised by Nathan. I hope it was not just his tainted views of pharmaceutical companies that influenced my decision. I left the room convinced that new insulins were not worth the money and should not be distributed routinely and across the board in the management of T2DM. I also believe that the bandwagon for nocturnal hypoglycemia has gone too far and lacks adequate justification in patients with T2DM.

We should not hesitate to prescribe standard insulins or be intimidated into using new analogues without discretion. In some sense, going back to the old insulins is going forward in the management of T2DM.

I will continue to keep a place for old and new insulins in my clinical practice. Haggling for fairer prices may be a skill that the United States needs to master as a means to reduce the cost of diabetes medications and break the confines so that insulin therapy can be readily available to all of those who need it.

Finally, we must congratulate the ADA for holding such a successful and stimulating debate. I believe, however, that this is a token response to a serious and growing diabetes problem in the United States, a view expressed by another member of the audience who received a loud applause for her comment.

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