As insulin prices rise, endocrinologists confront growing crisis
The number of Americans with diabetes continues to grow, along with the need for insulin therapy. Between 1997 and 2011, the age-adjusted percentage of adults with diagnosed diabetes prescribed both insulin and other antihyperglycemic agents increased from 9.1% to 13%, with another 17.8% prescribed insulin alone, according to the CDC.
Several new insulin therapies are now available or in the pipeline for 2017, including eight basal insulins, six prandial insulins and a “follow-on” product to insulin glargine, Eli Lilly’s Basaglar, approved by the FDA in December 2015.
In the past decade, estimated inflation-adjusted spending for insulin per patient tripled, from $231.48 in 2002 to $736.09 in 2013, according to an analysis of individual and prescription-level data published in the April 2016 issue of JAMA; those data combined both human and analogue insulins. The mean price per milliliter of insulin increased by 197%, whereas the mean price of dipeptidyl peptidase-4 (DPP-4) inhibitors increased by 34% from 2006 to 2013, and the mean price of metformin decreased by 93% from 2002 to 2013. The 2013 insulin cost, the researchers noted, was greater than expenditures on all other antihyperglycemic drugs combined, which was estimated at $502.57 in 2013.
Today, list prices for popular therapies such as insulin lispro (Humalog, Eli Lilly) and insulin aspart (NovoLog, Novo Nordisk) can reach $600 before applying any pharmacy or manufacturer coupons, according to the drug comparison website GoodRx.com.
Patients without health insurance, those with high-deductible plans or older adults who reach the temporary spending limit for their Medicare Part D drug plan — commonly known as the “donut hole” — often have no choice but to pay the high list prices, Irl B. Hirsch, MD, professor of medicine at the University of Washington School of Medicine in Seattle, told Endocrine Today. Patients who cannot afford their insulin, Hirsch said, sometimes restrict their use or, worse, forgo therapy entirely. Endocrinologists, he added, must find alternatives for these patients, who risk serious complications, including heart disease, stroke and kidney failure from poor glycemic control.
“The issues of why [insulin is expensive] and how do we deal with it and how do we fix it are three different questions, and all of them are complex,” Hirsch said. “The big issue with patient management is that the endocrine community needs to become more expert with the use of human insulin. More importantly than that, we need to teach our primary care colleagues how to more effectively use human insulin.”
“Even in my university clinic, where they require some type of insurance, I’m having patients call back and say, ‘I can’t afford this,’” David C. Robbins, MD, professor of medicine and director of the University of Kansas Diabetes Institute, told Endocrine Today. “I would say a fair percentage of people don’t take their insulin either as much, or at all, because of the cost.”
Robbins, who also volunteers at a free clinic serving uninsured patients, said the situation has worsened there.
“In the free clinic, it even goes a step further,” he said. “I’ve seen people sharing insulin with other family members — cutting it in half — or going without medication.”
The price hikes are also affecting patients with low-deductible health insurance, who are increasingly shouldering more of the cost for their drugs through higher copays, according to Henry Anhalt, DO, FAAP, FACE, FACOP, chief medical officer of T1D Exchange. Patients with type 1 diabetes, he said, are particularly rattled when they discover an insulin they may have used for years is no longer covered due to changes in the formularies — the lists of drugs covered by insurers and pharmacy benefit managers (PBMs).
“There are a lot of determinants that impact insulin pricing, but patients typically don’t see them,” Anhalt told Endocrine Today. “For the patient, what happens is it all gets translated as a letter that comes in the mail that says ‘this drug is no longer on formulary.’ So, the patient — especially one with type 1 diabetes, who sees the responsibility of managing their disease as wholly theirs — is now left in a situation where, once again, decisions are being made about their health care, and they don’t understand why.”
The rapidly rising cost of insulin therapy is directly affecting clinical management, experts told Endocrine Today. Patients who limit or forgo insulin therapy risk developing new or increasing complications that must be managed, and health care providers are devoting more time to help patients navigate formulary changes or find resources to assist with the increased cost burden.
For patients who cannot afford the list price for newer insulin analogues, the solution may involve “going backward” to the older — but still reliable — regular or NPH insulins that were commonly used before the introduction of insulin analogues in 1996, Hirsch said. The current retail cost for human insulin ranges between $25 and $150 for a vial, according to drug price comparison websites; Eli Lilly offers NPH insulin in pen form.
At retailer Walmart, NPH insulin, through a contract with Novo Nordisk, is available under the brand name ReliOn for $25 a vial.
“Whenever doctors complain to me about the cost of insulin, I recommend that they send their patients to Walmart,” Richard O. Dolinar, MD, of the Arizona Endocrinology Center in Phoenix and an Endocrine Today Editorial Board member, said in an interview. “When used correctly, you can get good control of diabetes with regular and NPH insulin.”
Some health care providers may be less inclined to recommend older insulins to patients due to a lack of training with those therapies, according to Robert Lash, MD, professor of internal medicine in the division of metabolism, endocrinology and diabetes at the University of Michigan and chair of the clinical affairs core committee for the Endocrine Society.
“When you talk to younger physicians about using NPH and the different ways we used to use NPH, they kind of look at you like, ‘And did you carve your prescriptions in stone, too?’” Lash told Endocrine Today.
Robbins agreed. “Part of the problem is we haven’t been trained how to [use NPH], and the drug companies haven’t given us the guidance,” Robbins said. “If you have someone on Lantus [insulin glargine, Sanofi], how many times a day do you have to give NPH to get an equivalent basal insulin level? Those data aren’t there.”
However, a switch to NPH insulin may not be the solution for every patient who cannot afford their insulin, according to Kenneth Snow, MD, an endocrinologist and medical director for northeast regional care management at Aetna.
“I’ve heard it on the provider side and I’ve heard it on the payer side,” Snow told Endocrine Today. “As a provider, there are clearly instances where newer insulins, because of specific properties, do add a significant value for a patient. And it gets to be a frank conversation with the patient about what is affordable and what is not. No product does any good if a patient doesn’t fill their prescription.”
Providers must carefully evaluate all insulin options to determine which product will provide the most benefit to a specific patient, he said.
“If product A has a slightly lower rate of hypoglycemia, but the goal for this patient is to have an HbA1c of 8% and the likelihood of hypoglycemia is small, is it really of significant value to start off with the more expensive prescription as opposed to starting off with possibly an older product — maybe an NPH — which for that person, because of what their needs are, should work equally well?” Snow said. “You don’t want to spend a lot more money for a benefit that you’re never going to get. And patients can understand that.”
Managing insulin changes
Patients who are faced with switching from one rapid-acting insulin to another due to a change in their branded insulin’s preferred formulary status may have to make some adjustments, but any changes are typically inconsequential, Robbins said.
“Some of the insulin changes are a big deal, particularly with the basals,” he said. “Levemir (insulin detemir, Novo Nordisk), for example, I don’t think is, unit-for-unit, equal to glargine insulin for some patients, and I dislike that when the insurance company [makes that switch]. Some us have concerns, too, with using Apidra (insulin glulisine, Sanofi Aventis), particularly in a pump, where in my experience it has not been as stable. I would put most of this in the category of aggravation, particularly for the patient, but the seriousness of [a change] is fairly unusual.”
The decision to initiate human insulin therapy brings its own caveats for patients and physicians, Hirsch said. NPH insulin, for example, is more likely to increase the risk for hypoglycemia in patients with type 2 diabetes vs. an analogue, meaning clinicians should caution patients about middle-of-the-night glucose checks and having snacks on hand for blood glucose lows.
“NPH is linked to making sure people don’t skip meals,” Susan Cornell, PharmD, CDE, FAPhA, FAADE, associate director of experiential education and associate professor in the department of pharmacy practice at Chicago College of Pharmacy at Midwestern University in Downers Grove, Illinois, told Endocrine Today. “I always say, ‘Whatever you’re doing 6 to 8 hours after that injection, it better be eating (to reduce the hypoglycemia risk).’”
NPH is also a suspension insulin, Cornell said, noting that practitioners may forget to tell patients that they need to make sure the insulin is evenly distributed in the vial.
“The newer grads coming out [of medical school] are taught how to use NPH, but not preparation or practice, because it’s hardly used,” she said. “If the patient is not rolling their insulin 20 times in the palm of their hand to suspend it, the dose is inaccurate. The dose is not a U-100 dose unless it’s suspended. And patients can be completely oblivious to this.”
Practitioners must also work with patients used to insulin pens to practice how to use a vial and syringe, she said.
“If practitioners can at least refer the patient to someone who can do it ... that’s where the voice and education skills of a CDE come in,” Cornell said.
But the new reality for patients has caused Hirsch to change his prescribing practices, he said.
“In our hospital now, for the typical patient with type 2 diabetes [not newly diagnosed] who is going to be starting insulin, our strong recommendation is going to be to start those patients on NPH now,” Hirsch said. “And the reason is that we saw those patients leave the hospital, and then they couldn’t afford the analogue. If they get out and they go back to their primary care provider and it turns out that they can then switch to an analogue, that’s great. But we don’t want anyone stopping their insulin because they can’t afford it. It’s a safety valve at our hospital, and I’m really proud of that.”
The promise of biosimilars
In December, Eli Lilly and Boehringer Ingelheim announced that their long-acting human insulin analogue, Basaglar, was available by prescription in the United States. It is considered a “follow-on biologic” insulin to Lantus and has an identical amino acid sequence, but it is not considered to be a biosimilar due to its FDA regulatory submission pathway via the federal Food, Drug, and Cosmetic Act. No insulin glargine products are currently licensed under the Public Health Service Act; insulins are approved and regulated as chemical drugs, so there is no “reference product” for a proposed biosimilar, according to the FDA.
Currently, any follow-on insulin must be approved under the abbreviated new drug pathway; the FDA plans to eliminate this pathway in 2020 when all biosimilar drugs will be licensed under section 351 of the Public Health Service Act.
The introduction of follow-ons like Basaglar may help to reign in the rising costs, Lash said.
“Basaglar has reset the game and put the first real price pressure on long-acting insulins,” he said. “Insurance companies are embracing it, even though it’s not that much cheaper than Lantus, to send a message that says, ‘We will reward you for making the commitment to a biosimilar.’”
“[I am] delighted to see Lilly come into the market with a basal,” Robbins said. “Whether or not it’s going to start a price war is anyone’s guess. It’s too complex — it’s not like having two gas stations on opposite corners — but it’s a step in the right direction. The holy grail of having true generics, like we do with some of the older drugs, is just not going to happen with insulin. It’s so expensive to make and ship. The market is always going to be a little bit different.”
Although regulatory pathways for biosimilar insulin are being finalized in the United States and Europe, economists warn that the introduction of biosimilars may not lead to price reductions equivalent to those seen with typical generic medicines, Jeremy A. Greene, MD, PhD, and Kevin R. Riggs, MD, MPH, both of the Berman Institute of Bioethics at John Hopkins University School of Medicine, wrote in a commentary published in the March 2015 issue of the The New England Journal of Medicine. That is because even an abbreviated approval process for biosimilars will require substantially more original data than the typical abbreviated new drug application required for small-molecule generics, they noted.
“Price reductions for biosimilar insulins in the United States are predicted to be about 20% to 40% — much less than the reductions of 80% or greater for most small-molecule generics,” Greene and Riggs wrote. “Europe, which has already approved numerous noninsulin biosimilars, has seen similarly disappointing price reductions in biosimilar products.”
Efforts to address pricing
Advocacy groups have stepped up efforts to raise awareness about the growing price problem. In December, the American Diabetes Association launched a new online hub advocating for insulin affordability, including a petition calling for congressional action on the issue. The new site — www.makeinsulinaffordable.org — is part of the ADA Stand Up for Affordable Insulin initiative, which launched in November. According to the website, more than 248,000 people have signed the petition to support those struggling with insulin affordability.
Drug makers have also responded to criticism with several new initiatives. Eli Lilly has partnered with Express Scripts to use its platform, Blink Health, to access price discounts on insulin via mobile and web platforms.
The program, which began Jan. 1, allows patients who pay full price for Lilly insulins to save up to 40%.
In a position statement on its website, Novo Nordisk notes that three tenets are key to make a positive impact on insulin affordability for patients: transforming the complex pricing system, creating pricing predictability and reducing the burden of out-of-pocket costs. The company states that it continues to maintain and invest in copay assistance programs.
Sanofi recently finalized its corporate pricing policy to reflect a “focus on value,” Sanofi spokesperson Anna Robinson told Endocrine Today. Goals include limiting price increases to National Health Expenditure projections and disclosing the aggregate gross and net prices of medicines to foster greater transparency, she said.
“We recently enhanced our copay program limiting out-of-pocket expenses to $10 for eligible Lantus and Toujeo [insulin glargine, Sanofi] patients regardless of formulary status or insurance coverage,” Robinson said. “This copay offer helps patients on traditional commercial insurance, including those on high-deductible plans, as well as those who pay cash.”
The patient-assistance efforts, Lash said, are a good start, but more must be done.
“It’s important for everyone who has a stake in this to realize that insulin prices will not come down until we make a concerted effort to bring them down,” Lash said. “That’s going to mean public pressure, looking for those best prices, looking at other cost alternatives. Patients and physicians and the providers have a lot more power in this story than we think we do. We just have to be willing to look for those opportunities and maybe endure a little inconvenience on our own part to avail ourselves of less expensive options. Because if there is price pressure, prices will come down.” – by Regina Schaffer
- American Diabetes Association. Stand Up for Affordable Insulin. Available at: makeinsulinaffordable.org/. Accessed May 31, 2017.
- Blink Health. Available at: www.lilly.com/blinkhealth. Accessed May 31, 2017.
- CDC. Age-adjusted Percentage of Adults with Diabetes Using Diabetes Medication, By Type of Medication, United States, 1997-2011. Available at: www.cdc.gov/diabetes/statistics/ meduse/fig2.htm. Accessed May 31, 2017.
- Greene JA, Riggs KR. N Engl J Med. 2015:doi:10.1056/NEJMms1411398.
- Hua X, et al. JAMA. 2016;doi:10.1001/jama.2016.0126.
- Novo Nordisk. Our Position on Pricing and Affordability. www.novonordisk-us.com/whoweare/about-novo-nordisk/our-position-on-pricing-and-affordability.html. Accessed on May 31, 2017.
- For more information:
- Henry Anhalt, DO, FAAP, FACE, FACOP, can be reached at T1D Exchange, 11 Avenue de Lafayette, Fifth Floor, Boston, MA 02111; email: firstname.lastname@example.org.
- Susan Cornell, PharmD, CDE, FAPHA, FAADE, can be reached at Midwestern University Chicago College of Pharmacy, 555 31st St., Downers Grove, IL 60515; email: email@example.com.
- Richard O. Dolinar, MD, can be reached at the Arizona Endocrinology Center, 15640 N. 28th Drive, Phoenix, AZ 85053; email: firstname.lastname@example.org.
- Irl B. Hirsch, MD, can be reached at University of Washington Med Center – Roosevelt, 4245 Roosevelt Way NE, Third Floor, Box 354691, Seattle, WA 98105; email: email@example.com.
- Robert Lash, MD, can be reached at the University of Michigan, 3101 Taubman Center, SPC 5368, 1500 East Medical Center Drive, Ann Arbor, MI 48109; email: firstname.lastname@example.org.
- David C. Robbins, MD, can be reached at the University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160; email: email@example.com.
- Anna Robinson can be reached at Sanofi US, 55 Corporate Drive, Bridgewater, NJ 08807; email: firstname.lastname@example.org.
- Kenneth Snow, MD, can be reached at 151 Farmington Ave., Hartford, CT 06156; email: email@example.com.
Disclosure: Anhalt is chief medical officer of T1D Exchange and chairman of the Hormone Health Network, part of the Endocrine Society. Dolinar reports serving on the speakers bureau for Eli Lilly and receiving editorial writing support from Sanofi. Hirsch reports receiving consultant fees from Abbott Diabetes Care, Intarcia and Roche Diagnostics. Lash reports consulting for Express Scripts. Robbins reports owning shares of Eli Lilly. Robinson is an employee at Sanofi. Snow is medical director for Aetna. Cornell reports no relevant financial disclosures.