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Diabetes Forecast

The Healthy Living Magazine

Can Switching From Analog to Human Insulin Save You Money?

Why some people with diabetes are giving up newer analogs and using human insulin instead

By Allison Tsai , ,

Terry Doran/Mittera

If you don’t take your multivitamin every day, it’s not the end of the world. But if you skip your insulin, you put your health at risk. Unfortunately, as the price of insulin rises, some people are forced to ask an impossible question: Do I make ends meet or buy the insulin I need?

“Not only are [insurance] premiums getting higher, [but] deductibles and copays are getting higher. And the price of drugs is the highest ever, so people are not taking their medications,” says George Grunberger, MD, FACP, FACE, chairman of the Grunberger Diabetes Institute and clinical professor of internal medicine at Wayne State University School of Medicine in Detroit. “[These patients have] been on insulin many years, and yet, for the first time in their lives, they have to make these kinds of decisions.”

Switching from pricey analogs to the older, lower-priced human formulas may be an option for some people with diabetes. But does the lower price of human insulin offset potential drawbacks?

Human Era

To understand the term “human insulin,” you have to consider the history of insulin production, says Evan Sisson, PharmD, MSHA, CDE, FAADE, an associate professor at Virginia Commonwealth University School of Pharmacy and a spokesman for the American Association of Diabetes Educators. “When insulin was first purified to be used in humans, it was actually coming from animal products,” he says. As cows and pigs were slaughtered, workers would save the pancreases. Once two tons of pig parts were collected, they would crush them and eventually extract 8 ounces of purified insulin.

In the 1970s, researchers discovered how to program bacteria in the lab to manufacture human insulin, and in 1982, regular human insulin became the first “recombinant DNA” drug product. “It’s a very pure, clean product, and it’s exactly what we as humans make,” Sisson says. Human insulin is now available as short-acting “regular” (or “R”) insulin, which is used at mealtimes, and intermediate-acting NPH (or “N”) insulin, which is used as a basal insulin. A big difference between the two? NPH insulin needs to be mixed, at which point it becomes cloudy due to insulin-protein microcrystals. Those teeny crystals slowly dissolve at the injection site and prolong the release of insulin into the bloodstream.

Analog debut

While the development of human insulin was a major advancement, it wasn’t perfect. Regular insulin didn’t hit the bloodstream quick enough to cover the rapid absorption of carbohydrates after meals, and it stuck around too long after meals, causing hypoglycemia. In 1996, Eli Lilly introduced the first rapid-acting insulin analog to the market: insulin lispro (Humalog). Insulin aspart (Novo Nordisk’s Novolog) and insulin glulisine (Sanofi’s Apidra) quickly followed. With rapid-acting insulin analogs, onset occurs 10 to 20 minutes after injection, instead of the 30 to 60 minutes it takes for regular human insulin to take effect. This allows people to inject their insulin right before a meal, rather than having to dose 30 minutes or more before eating.

But scientists, and people with diabetes, were still eager for more long-acting insulin options—versions that wouldn’t have NPH’s peak (which can cause hypoglycemia hours after injecting) or fairly short duration. They modified the insulin molecule to be absorbed more slowly and consistently from the insulin injection site. The result: long-acting analogs such as insulin glargine (Lantus), insulin detemir (Levemir), and last year, Basaglar, which is a newer form of insulin glargine by a different manufacturer. These newer, long-acting insulins work in the body for 20 to 26 hours and typically permit once-daily dosing. Newer ultra-long-acting insulins—degludec (Tresiba) and glargine (Toujeo)—last even longer.

Insulin Comparisons

With all of these insulins on the market, it’s hard to know which is best. Studies have shown that analogs have some advantages over human insulins, but not all experts agree they’re the best choice for everyone. Three experts weigh in on important factors to consider when prescribing types of insulin:

Hypoglycemia

Deliver a dose of NPH insulin, and it’ll reach its peak about six to eight hours later. This means your insulin may peak while you’re sleeping, posing a serious danger if you don’t wake up to treat. Long-acting analogs, on the other hand, don’t peak, resulting in more-stable blood glucose levels and fewer unexpected highs or lows. In fact, one study showed that long-acting analog insulin glargine reduced overnight bouts of hypoglycemia by up to 48 percent compared with NPH. In another study, detemir reduced nighttime hypoglycemia by 34 percent. This is especially beneficial for people with type 1, who need to be much more precise about matching insulin dosages with their insulin needs to avoid nighttime lows, says Sisson.

But for people with type 2 diabetes who are capable of some degree of insulin production, it’s less clear whether the benefits of analog insulin warrant the higher price, says Mayer Davidson, MD, professor of medicine in the Department of Internal Medicine at Charles R. Drew University in Los Angeles. According to the American Diabetes Association 2017 Standards of Medical Care in Diabetes, people with type 2, and without a history of hypoglycemia, may use NPH as basal insulin safely and at a much lower price than analogs. Davidson also says that people taking human insulin can potentially avoid overnight hypoglycemia by eating a bedtime snack, such as an apple with a tablespoon of peanut butter, something he strongly recommends to his patients.

Inject regular insulin at mealtime, and it’ll stick around longer after eating, upping your risk for delayed lows, says Grunberger. Because regular insulin peaks two to four hours after injection, people with type 1 who take it have to be careful about activity a few hours after meals. If you decide to take a long walk two hours after dinner, you may end up having a low in the middle of your walk. Injections of regular insulin for your evening meal can also increase the risk of overnight hypoglycemia.

The 2017 Standards of Medical Care recommends that most people with type 1 use rapid-acting insulin analogs (which leave the body in about four hours) to reduce hypoglycemia risk. However, for people with type 2 who are still able to produce insulin, this isn’t as much of an issue. “What you do is consistently under-dose them a little bit so that their pancreas makes up the difference,” says Sisson.

Weight Gain

The peak and duration of human insulin may create a need for more snacking during the day to prevent lows, says Grunberger. This can increase caloric intake and cause weight gain. Davidson suggests this workaround: Eat fewer calories at meals to offset calories from snacks during the day.

Convenience

When it comes to meals, regular insulin requires a bit of planning. It needs to be injected 30 to 45 minutes before you eat, says Grunberger. Rapid-acting analogs, on the other hand, allow you to inject right before eating, offering more flexibility in your schedule. You can even inject the analogs after a meal, adjusting the dose to cover what you ate, although blood glucose will be slightly higher after the meal using this approach.

Effectiveness

All types of insulin lower blood glucose effectively. From a user perspective, the logistics of analogs are much simpler: You can inject your mealtime insulin immediately before the meal, and you generally have one daily basal insulin injection. (Glargine and, more often, detemir sometimes have to be given twice daily for maximum efficacy.) There are other benefits to analogs over human insulins—namely less hypoglycemia. Rapid-acting analogs also lead to slightly lower after-meal glucose levels. Even so, good control of blood glucose levels can be attained with human insulins in most cases.

Those benefits, however, do not necessarily translate to a better A1C (a measure of how well your diabetes is controlled over a period of time), says Davidson. “The right insulin depends on when you want the insulin to peak, how long you want it to last, and, honestly, what insurance company you have and how you are going to pay for this stuff,” Sisson says.

The Cost Conundrum

Rising insulin prices have caused many people to question what necessities they’ll do without to be able to pay for their meds. “No one in need of lifesaving insulin should ever go without it due to prohibitive costs,” says Desmond Schatz, MD, immediate past president of medicine and science at the American Diabetes Association. In November 2016, the Association issued a resolution and launched a petition calling for access to affordable insulin.

Worldwide, the analogs are 2½ times more expensive than human insulins, says Davidson, who has been tracking the wholesale cost of insulin for six years. From 2011 to 2015, the average wholesale price of a box of five disposable insulin glargine pens (300 units each) went from $234 to $447, a 91 percent increase. A 10-milliliter vial (1,000 units) of the same insulin rose from $121 to $298—a 146 percent price hike. Some of the rapid-acting analogs jumped by as much as 88 percent, raising the cost to more than $500 for a box of disposable pens (300 units each) in 2015.

Human insulin is rapidly increasing in price, too. Regular and NPH jumped from about $66 for a 10-milliliter (1,000-unit) vial to $144.72 between 2011 and 2015—a 118 percent jump. Human insulin is considerably cheaper because the price started out much lower, says Davidson.

Also, while human insulin may have a lower wholesale price tag than analogs, insurance coverage will ultimately dictate the cost to the consumer. Some drug companies have suggested that many people pay less than wholesale prices due to rebates that are privately negotiated between the pharmaceutical companies, pharmacies, and pharmacy benefit managers—middlemen who work for commercial and government-run health plans to negotiate drug prices—and payers such as insurance companies, Medicare, and Medicaid.

Advocates, however, say that is not always the case. Whether you have a high-deductible insurance plan, a gap in Medicare drug coverage (called the donut hole), or pricey drug co-pays, people with diabetes are increasingly feeling squeezed by these price hikes. “Insulin has become obscenely expensive,” says Grunberger. “The longer they’ve been on the market, the more expensive they become,” he says.

All three insulin companies—Eli Lilly, Novo Nordisk, and Sanofi—have raised their prices in lockstep every year. When one company increases the price, the other two follow suit with a similar increase. The price hikes have become so excessive that in November, Sen. Bernie Sanders (I-Vt.) and Rep. Elijah Cummings (D-Md.) called on the Department of Justice and the Federal Trade Commission to investigate possible collusion among the insulin companies.

Making the Switch

Many providers are switching patients from analog to human insulin due to its lower cost, and the cheapest options are the regular and NPH products, which retail at Walmart for $25 per 1,000-unit vial. You can find it under the names ReliOn Novolin R, ReliOn Novolin N, and ReliOn Novolin 70/30 (70 percent NPH/30 percent regular). Brand-name human insulin is available from other pharmacies, though the cost varies and is typically higher.

James MacDonald, 51, switched from insulin glargine to branded 70/30 human insulin because he could no longer get insulin glargine through the patient assistance program at Sisson’s clinic. The swap worked well for MacDonald, who has type 2, but his financial struggles were just beginning. He lost Medicaid eligibility, which meant he had to buy his own insurance. He went from paying nothing for his insulin to shelling out over $700 a month with his new policy. “It would cost $120 a vial, and I need six vials a month to live,” he says. He has since discovered the ReliOn brand and has kept his A1C at 6.5 percent.

In most states, human insulin requires no prescription, says Grunberger. If you take a large daily dose of insulin and have insurance, check to see if it covers ReliOn insulin, or if your out-of-pocket expenses for ReliOn would be lower than your co-pay for branded insulin.

Beware: If you’re buying your insulin out of pocket from a pharmacy like Walmart, some insurers may no longer cover your test strips because you’re no longer getting insulin through insurance. Instead, you’ll be covered as someone with type 2 who’s not on insulin therapy. Private insurers and Medicare typically pay for only one test strip per day for those not on insulin therapy. Work with your doctor to get what you need.

Competitive Boost

Researchers say people with diabetes can expect more follow-on biologics—the equivalent of a generic for drugs that are made from living material, like insulin; Basaglar is one example—for insulin to enter the marketplace in the near future. That would result in greater competition among brand-name insulins, potentially helping to bring down costs and lessen the financial burden for many families.

Check out the wholesale price of insulins.

Go to care.diabetesjournals.org/insulin_cost.

Find out more about the rising cost of insulin.

Stand Up for Affordable Insulin

Join more than 150,000 others and sign the American Diabetes Association’s petition at makeinsulinaffordable.org. You’ll also find resources to help you pay for insulin, a place to share your story, and more.

 
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