Andrew Smith

JDRF’s mission is to seek new treatments for type 1 diabetes (T1D), but the skyrocketing costs of existing insulin formulations have hurt so many patients that the new CEO of the 50-year-old organization has asked legislators to reduce the cost of currently available medications. The JDRF officially backs a new bill that would ban rebates on insulin formations that sell above their 2006 prices.

Aaron Kowalski, PhD, said in an interview with 

 that action is needed not only by Congress, but also by insulin makers, health plans, and the executive branch. The most important goal: ending a crosspayment scheme that many blame for potentially deadly price increases.

“We see the issues related to the rebate system as being the biggest challenge for us right now,” Kowalski said. “In a normal capital market where you have at least 3 similar products, as we do for most types of insulin, you’d see competition driving retail prices down. The rebate system lets the 3 insulin makers chase the prices up rather than chase them down. It hurts everyone, but it is extremely painful to people who are uninsured, who are underinsured, and who have high deductibles or copays.”

Pharmaceutical companies and payers keep nearly everything related to drug costs as confidential as the law allows, so many market specifics remain unknown, but the basics seem clear:

Drug makers typically revise each product’s list price about once a year and then negotiate rebates with each of the health insurers and pharmacy benefits managers (PBMs) that buy those products.

Insurers and PBMs negotiate rebate size aggressively, but they have no reason to ask drug makers to lower the list prices they never pay. No other organization has power to get drug companies to lower list prices, so those prices rise. A lot.

Researchers estimate that the price of a 40-day supply of insulin rose from $344 in 2012 to $666 by 2016.

 Out-of-pocket insulin costs for Medicare patients have more than quadrupled since 2007.2

It’s unclear what effect the rise in list prices has had on major payers. They may be negotiating such good rebates that their net insulin costs have risen very little, if they have risen at all. But skyrocketing list prices have hammered people who pay list prices or make copayments that are based on list prices—even very affluent people. Kowalski, the first CEO of the JDRF who has T1D, has seen it up close.

“My brother is a successful architect who runs his own business, but it’s a small business, 15 people or so, and his deductible was $12,000 or $14,000 a year,” Kowalski said. “His wife switched jobs for insurance because he was paying out of pocket for this insulin, at full list price, until he hit his deductible every year. He is a successful business person, but paying $300 a vial, multiple times a month, is a life-altering cost. For anybody who is living on a more normal income, which is the bulk of our population, that is an incredibly painful price for a drug that sustains your life.”

The legislation, whose primary sponsor is US Senator Jeanne Shaheen, D-New Hampshire,  is also supported by the American Diabetes Association. It would restrict the use of rebates, both in Medicare Part D and the private insurance market, for insulins whose list prices were initially rolled back to 2006 levels and then increased at no more than the general rate of medical inflation. The legislation would also require private insurance plans to waive deductibles for medications whose list prices fell to the required levels.3

“If that passes and all goes as expected, that would drive list prices down about 70%, but prices would still be considerably higher than they are in Canada, where people are paying about $40 a vial,” Kowalski said. “During recent Congressional hearings, the manufacturers admitted they were making money at the Canadian price. They’re not giving away insulin or selling it at a loss. And that tells us that there is plenty of room for profitability at 30% of current prices.”

Even if this particular bill does not pass, Kowalski believes there’s a very good chance that patients will get some relief.

“We have been encouraged that there is bipartisan anger at the situation that we’re in,” he said. “I’ve talked about this in both the House and Senate, and both sides of the aisle are very frustrated, as are both President Trump and the Democratic candidates [for president]. The reason for this support is that diabetes doesn’t affect only [Republicans or Democrats]. It affects both, and that should drive a bipartisan effort to help fix this problem.”

The US patent and market exclusivity systems attempt to balance the need for innovation and affordability in the drug market. Patents award a 20-year period of patent protection at any time during the development of a new drug before (theoretically) allowing generics or biosimilars to the market. Exclusive marketing rights are granted by the FDA upon approval of new drugs, the length of which depends on the type of product. Patents and exclusivity are separate and may or may not run concurrently. Analysis from JDRF’s health policy team, among others, has convinced Kowalski that pharmaceutical companies have undermined this balance with tactics that range from gaming the patent system for longer protection to bribing would-be competitors not to compete.

“We at the JDRF believe that the key to getting pricing down further is to get more biosimilars to market, increase competition, and provide more options to patients, but, frankly, we’re fairly disappointed at the pace that the biosimilar market has played out in the United States,” Kowalski said. “The same seems to be true for the senior leadership at the FDA. They seem very committed to doing everything possible to get biosimilars to market as quickly as they can without compromising the quality of the product, so the real problem here seems to be the aggressive use of the patent system and everything else that companies do to keep competition off the market. It’s definitely a problem, but we haven’t taken a stance on how to fix it because we are focusing on the rebate issue first.”

The price of patent-protected drugs in the United States tends to be 20% to 40% higher than in other rich nations, and there are many economists who believe that reducing American prices would greatly reduce development spending by pharmaceutical companies, which currently make about half of all their profits here.

 The insulin market may be different, however, as the price premium on insulin formulations is much greater. Insulin prices here can be more than 10 times what they are in Canada, and prices remain way above production costs for medications that have been off patent for years. As a result, there is much more room for cutting prices while maintaining incentives for innovations that Kowalski says are still very badly needed.

“Insulins have improved greatly over the past few decades, but there is still a lot of room for improvement,” he said. “Today’s insulins are easier to use, but they’re still too difficult, and we know that from data. The bulk of people don’t get to target A1C [glycated hemoglobin] levels because dosing insulin is like walking on a tightrope. If you use just a little too much, you have hypoglycemia, which is immediately dangerous. If you use just a little too little, you have hyperglycemia, which brings about long-term complications. Insulins also work faster than they used to, but they’re not even close to what the body can do. We’d certainly like a faster-acting insulin. We’d also like what some people call a smart insulin, a product that only reacted when your blood sugar was high. We need innovation, so we do need enough profit to be made for innovation. But we also need fair pricing once things get to market.”

Although the JDRF hopes that dramatic price cuts will soon allow anyone to go to their local pharmacy and load up on the most sophisticated insulins, Kowalski says there are workarounds for people who cannot buy such products at current prices.

“No one should be using so little insulin that they put their lives in jeopardy. There are options,” Kowalski said. “For people who live near Canada, that is an option. I have a friend who is a doctor in Seattle, and he says that nearly half of his patients who need insulin get it in Canada, where the price of analogue insulins is about $40 a vial.”

Community health centers can provide help, too, as can company drug assistance programs (the JDRF has listed information at jdrf.org/insurance). Another option is using older insulin formulations.

“I went out for my daughter’s graduation this May, and I realized I didn’t have insulin with me. I have good coverage, but I had just filled my prescription, so my options were to pay cash for the insulin I normally use or to go back to the nonanalogue human insulin that I used back in the 80s or 90s. I chose the old insulin because it was much cheaper. You can buy it at Walmart for about $25 a vial, and it’s a genuine alternative. If your options are full doses of cheap, nonanalogue insulin or way too little of the newer formulations, the older insulin is clearly the better option. It will keep you alive.”

But it’s nothing like a perfect solution.

“It simply isn’t as good,” Kowalski said. “I’m a PhD scientist, I work in the business, and I had more than a decade of experience using these formulations before analogue insulins came around, but my blood sugar was still an absolute mess when I was using that older formulation.”

Importing medicines from Canada also has obvious difficulties for individuals. As for reimportation at the national level, which President Trump recently proposed, Kowalski believes there has to be a better way to drive prices down.

“It shouldn’t come to that,” he said. “It is silly to devise this Rube Goldberg system for sending drugs from here to Canada and bringing them back to here. We need systemic change.”

JDRF’s very public advocacy for price-reducing measures from Washington has been well received by other advocates for patients with T1D. Some of those advocates have accused the JDRF of shying away from stances that would upset the pharmaceutical companies and device makers that are developing the next generation of treatments and that donate some money to JDRF coffers—a criticism that Kowalski says is utterly unfounded.

“I strongly object to that characterization. The dollars we receive from pharmaceutical companies or other companies in the medical field make up a tiny fraction of our budget; I believe it’s less than 3%. And those are unrestricted grants or targeted to educational programs that we run,” Kowalski said. “That amount of money wouldn’t affect decisions anywhere, let alone at an organization that is governed by people who have type 1 diabetes and people whose children have type 1 diabetes. Parents whose children have type 1 diabetes are not going to compromise patient care for pharma dollars. That money has no effect on any of our decisions. This organization is driven by a passion for helping people with this disease, not for seeking corporate support.”

Hargraves J, Frost A. Price of insulin prescription doubled between 2012 and 2016. Health Care Cost Institute website. healthcostinstitute.org/blog/entry/price-of-insulin-prescription-doubled-between-2012-and-2016. Published November 29, 2017. Accessed August 19, 2019.

Cubanski J, Neuman T, True S, Damico A. How much does Medicare spend on insulin? Kaiser Family Foundation website. 

kff.org/medicare/issue-brief/how-much-does-medicare-spend-on-insulin/

. Published April 1, 2019. Accessed August 19, 2019.

Summary of the Insulin Price Reduction Act. Senator Jeanne Shaheen, D-New Hampshire, website. 

shaheen.senate.gov/imo/media/doc/Insulin%20Price%20Reduction%20Act%20Summary.pdf

. Published July 22, 2019. Accessed August 19, 2019.

Goldman D, Lakdawalla D. The global burden of medical innovation. The Brookings Institute website. 

brookings.edu/research/the-global-burden-of-medical-innovation/

. Published January 30, 2018. Accessed August 19, 2019.

Articles

Aaron Kowalski, PhD, the new CEO of the JDRF, says in a discussion about insulin pricing that action is needed not only by Congress, but also by insulin makers, health plans, and the executive branch. The most important goal: ending a crosspayment scheme that many blame for potentially deadly price increases.

JDRF's Kowalski Sees Hope in Bipartisan Support for Insulin Pricing Reform

Andrew W. Lo, PhD, the Charles E. and Susan T. Harris Professor at the MIT Sloan School of Management, has a wide variety of research interests. He's best known in the healthcare world for ideas that could greatly increase the development of new drugs and access to expensive cures. The director of the MIT Laboratory for Financial Engineering, Lo is a principal investigator at the MIT Computer Science and Artificial Intelligence Laboratory and an affiliated faculty member of the MIT Department of Electrical Engineering and Computer Science. He is a past winner of the Battermarch, Guggenheim, and Sloan fellowships and has been named one of the 100 most influential people in the world by 

His proposals seek to increase investment in medical innovation and utilization by giving investors many more ways to support both research organizations and individual patients. For example, Lo sees opportunities for attracting new investment via securitization, the practice of combining individually risky assets into large pools that provide more predictable returns. The resulting cash flows are then divided into tiers based on levels of risk and reward favored by different investors.

Lo’s proposals typically rely solely on investors, drug developers, and patients acting in their own self-interest to produce the desired outcomes. However, he does see some opportunities for relatively small investments by philanthropies or the public sector to produce outsized returns in areas like pediatric cancer, where traditional finance tools would not be enough to attract socially optimal levels of investment. Indeed, by simply protecting private investors against loss during the riskiest phases of pediatric drug development, charities or governments may secure far more investment than they could fund on their own.

 This concept was presented in June at the American Society of Clinical Oncology annual meeting,

with full results published in September in 

) spoke with Lo about his ideas, including those in his recent paper.

: How did you get interested in how we finance drug development and usage?

It was really for personal reasons. A few years ago, a number of friends and a family member were dealing with different types of cancer, and it was through the process of trying to understand what they were dealing with that I realized that finance actually plays a pretty significant role in drug development.

For example, even though we seem to be on the verge of a number of breakthroughs in how we deal with these diseases, funding for early-stage drug discovery is actually getting scarcer. Why do we see this so-called “Valley of Death” for preclinical [research and development] and phase 1 clinical trials? In trying to make sense of this conundrum, I began doing research on the economics of the biopharma industry and realized that we could actually make a difference for patients if we used better methods for financing drug development.

My conjecture, which now has substantial supporting evidence, is risk. Drug development is really at its riskiest between the preclinical stage and phase 2 clinical trials. As financial pressures have increased on drug companies and venture capitalists [VCs] to improve performance, the response has been to focus on better bets, bets that are more of a sure thing. This means waiting until drug development projects reach certain milestones before investing.

Another risk that drug companies face is the risk that—thanks to all the recent biomedical innovation that’s been going on&mdash;a better drug gets developed, destroying the valuable franchise that these companies have invested billions in. We see this happening now with gene therapies that are on the verge of curing certain diseases that used to be chronic manageable conditions. It’s going to be a very interesting market dynamic as we see patients choosing between one kind of therapy and another and what kinds of pricing policies will emerge.

Despite those risks, overall returns on drug development are high enough to suggest we’re not investing nearly enough in it.

Drug development has 3 unique characteristics that, taken together, make it very challenging for investors. First, it takes a long time: typically 3 to 5 years before you hit the first major milestone and 10 to 15 years until you get an approved therapy. Second, it takes a large amount of capital to bring a single product to market, typically 1 or 2 orders of magnitude more than you need for start-ups in other industries. Third, the success rate is very low, about 5% in oncology for example, based on historical data.

There’s a small group of traditional biotech investors that are very sophisticated and understand how to manage these risks, but the larger pools of capital from ordinary investors that have been rushing into other areas like technology, social media, or cryptocurrencies simply aren’t there for this market. This is where the opportunity lies for better financing. If you structure the investments differently, you can make biotech attractive to more people and draw more money into drug development.

There are actually 2 ideas that have been used for decades in other industries and demonstrated the ability to reduce risk and improve average returns for investors. The first idea is “multiple shots on goal,” to use a hockey or soccer analogy. If you put together series of investments into a single financial vehicle, you are, in most cases, going to be able to reduce the risk and increase the likelihood that you have at least 1 or 2 successes. And in biomedicine, you only need 1 or 2 approved drugs to pay for all the other tries and still earn significant profits for investors.

But to create a large enough portfolio of multiple shots on goal, you need [a] much larger scale than the typical VC would have— on the order of billions of dollars in the case of cancer therapeutics, rather than a few hundred million dollars. This is counter to the traditional VC view that “small is beautiful.”

Which brings us to the second idea: using different kinds of financial instruments to fund these multiple shots on goal. Traditionally, biotech VCs use convertible preferred debt and then eventually equity to finance these start-ups. That’s certainly the tried-and-true approach. But to create a large enough portfolio of multiple shots on goal for drug development, you need to attract more capital, and the way to do that is to offer different kinds of securities. You can divide the underlying portfolio of assets—claims on future drug sales of multiple drug targets&mdash;in ways that let you sell low-risk, low-return bonds to investors who want safety, higher-risk equity to investors who want to gamble for big returns and every other type of security for investors who fall somewhere in between.

: You also believe that finance can increase utilization of expensive short-term treatments that either cure diseases or provide lifelong benefits. The idea is to find pools of capital that would be used to lend patients money that could be paid back over time.

Yes, but that’s not the new idea. It’s being done right now for all sorts of elective surgeries. Dental reconstruction is a good example. The typical cost of full-mouth reconstruction can range from $20,000 to $50,000, and candidates for these kinds of procedures can get consumer loans to pay for them right now.

What’s new in our proposal is to do this on a much larger scale, greatly increasing patient access to costly therapies, and to be able to securitize and package these “healthcare loans” and sell them to investors who are perfectly happy to take on large pools of diversified kinds of risks. Again, the investors get multiple shots on goal, but in this case, you’re talking about multiple consumer loans or loans to health insurers.

The idea really came about because of the possibility of curative gene therapies as well as other shorter-duration treatments like Sovaldi and Harvoni, 12 weeks of pills that can cure hepatitis C. Taking traditional medications is like renting an apartment: You pay for your benefit a month at a time and keep on paying as long as you want to live in that apartment. New medications like gene therapies are more akin to buying a house. You pay the whole cost up front and the benefit lasts for many years. But most people can’t afford to pay for the entire house in cash, so they get a mortgage, and that’s what we’re talking about here: drug mortgages. It’s the difference between “renting health,” one pill at a time, versus “buying a cure” and paying for it in installments.

The reason that this is an interesting approach is not just because it makes expensive one-time therapies more affordable for patients and payers. It can also serve as a way of dealing with cures that don’t really cure. We don’t yet know how permanent the effects of gene therapies really are; they’re supposed to be permanent, but we don’t have any real experience to rely on. What if it turns out that, after 2 or 3 years, the “cure” stops working and the patient relapses? Well, if you’ve paid for the therapy through a drug mortgage, you can simply stop making payments. That aligns the interest of the drug companies with the patients and the payers.

Based upon some very simple simulations that we’ve run by paralleling this submarket with the student loan market, we think there are tremendous amounts of resources that could be devoted to increasing patient access to these kinds of therapies. And with the 300-plus gene therapies currently in clinical trials, this is only the beginning of a huge wave of cures coming to patients over the next few years.

: You have also explored the idea that insurance companies, rather than patients, would take out these loans.

Yes, the idea of stretching out payments over a period of time is pretty straightforward, but the big question is who’s going to be paying that mortgage, and the natural response is insurers. That’s why we have health insurance.

The problem is that insurers expose themselves to potentially huge losses when they make large up-front payments for treatments that provide their policyholders with decades of benefits. This wouldn’t be true if policyholders always stayed with the same company. If you pay for a cure for one of your policyholders and that policyholder now lives for the next 30 years instead of dying in 1 or 2 years, you’ve got 28 more years of premiums that you can use to offset the cost of this cure.

But in practice, that policyholder can leave her health plan at any time. Suppose she moves to another state after only 5 years. So now, instead of having 28 years of premiums, you’ve only collected 5 years’ worth; the remaining 23 years of premiums go to an insurer in another state. That insurer will benefit from a healthy policyholder who’s now cured of this disease, thanks to the previous insurer. She may have other problems, but that’s one really serious disease that the new insurer doesn’t have to pay for.

There are a number of ideas for solving this patient-migration problem through regulation or legislation to protect insurers. This is critical because insurers are going to be very reluctant to finance expensive cures until they’re protected against this scenario. And currently, they’re the only ones who have the resources to finance the most expensive cures.

: Because the idea of lending money directly to patients doesn’t work when the loans get much bigger than $40,000?

Exactly. There are very few patients that can afford million-dollar therapies. And we’re now on the verge of developing a gene therapy for hemophilia. The best guess today for that price tag is about $1.5 million. There are few enough people who can afford $1.5-million homes, never mind $1.5-million drugs. And in the case of a home, at least there’s some pretty substantial collateral. In the case of your health, it’s very difficult to repossess a lung, so that’s why we used student loans as a model for this market: You purchased a college education, but they can’t really repossess your math courses. That’s why, ultimately, insurance companies are the ones that will be taking out these loans, and we need to deal with the patient-migration issue that they face.

: Talk about the research on how you could use these financial tools on pediatric disease, particularly cancer. Why doesn’t the market work now, and how can finance improve it?

Ironically, I think part of it is because we care so much about our children. Traditionally, pharma companies have not developed drugs for children exclusively. They start with adults for the simple reason that drug testing is a very dangerous business that often involves toxic side effects. Patients do die in clinical trials, so it’s a matter of ethical consideration to have adults take on these risks first before we expose children to them. But the consequence of that kind of ethical perspective is that pediatric oncology drugs are harder to come by. Drug developers will focus first on adults and unless, and until, they develop a successful therapy, they won’t try it on children. Now that’s changing, particularly with recent legislation requiring drug companies to develop therapies for adults and children simultaneously. But historically it’s been a challenge.

It’s also harder to develop pediatric oncology drugs because children have far fewer mutations than adults, implying fewer genetic biomarkers and druggable targets. Also, the biology of a 5-year-old can be quite different from that of a 12-year-old, and both are different from the biology of an adult, so it can be more complex to develop therapies for pediatric indications. Finally, the smaller patient populations make the economics of pediatric cancer drugs less attractive than those of adult counterparts, even with incentives like priority review vouchers and orphan drug designation. We ran the numbers and were shocked to discover that the simulated rates of return for pediatric oncology drug-development programs typically yielded double-digit negative returns on capital. Companies still do develop pediatric cancer drugs, but it’s probably more for ethical than financial reasons. And while it’s laudable that companies and investors still do invest in pediatric cancer drug development, they don’t invest nearly enough because the financial risk/reward profile isn’t very compelling.

Our proposal to get more investment into this field is a public—private partnership where the government and/or philanthropic organizations get involved in funding some of the riskiest parts of the development chain, preclinical R&D and phase 1 trials, and then hand it off to the private sector for completion after phase 1. We found that relatively reasonable amounts of public-sector funding, certainly much less than what goes into other areas of the drug development, could actually go a long way toward making the private sector interested in these kinds of health issues. Now that our paper is published (including our simulation software), our hope is that it’ll attract the attention of industry participants as well as philanthropic organizations and government agencies and that might spur them to collaborate with private-sector investors and biopharma companies.

: If you were the Trump administration’s health policy czar, what’s the first thing you would do?

The first thing that I would do is to use the convening power of the White House to bring together various stakeholders to work together collaboratively to develop solutions to some of the biggest medical challenges facing our country. The 3 areas I would prioritize are Alzheimer’s, infectious diseases, and antibiotics. These 3 areas present huge challenges, both current and pending, not only for our country but for the world, and they’ve gotten far too little resources and attention to date. As we saw with the Biden Cancer Moonshot, the White House can be extremely effective in coordinating the efforts of various groups to deal with the biggest issues facing humankind.

 How could things improve on the regulatory side?

Having now spent some time interacting with the FDA, I have to say that I’m incredibly impressed by the quality of their staff, their dedication, and how effective they’ve been. One of the most surprising things about them is their openness to new ideas and constant focus on improving “regulatory science.” To that end, I’ve been collaborating with several of their researchers to incorporate patient preferences into drug approval decisions. The standard approach for weighing the evidence from a clinical trial is to use a fixed statistical threshold of significance, also known as a 

 value or false positive rate, of 5% to determine whether a treatment is meaningful. Clinical trials with treatment effects that have a 

 value lower than 5% have traditionally been interpreted as statistically significant and those with higher 

 values are interpreted as insignificant. This 5% threshold is almost always applied across all diseases, but there’s reason to think that patients would be better served if the threshold were disease-specific.

For example, if we’re dealing with a disease that’s not particularly life-threatening, say acne medication, using a threshold of 5% for screening out false positives may be perfectly reasonable. But if we’re dealing with a potential therapy for a deadly disease like glioblastoma or pancreatic cancer where there’s currently no existing effective therapy and patients are likely to die anyway, patients might prefer to take more of a risk of a false positive so as not to miss a potentially effective therapy. We’ve developed a method for calculating the optimal threshold of false positives, given the severity of a disease and patient preferences regarding the costs and benefits of false positives versus false negatives. The FDA has been collaborating with us to construct a practical version of this framework.

: What are you doing to get your ideas for financing healthcare put into practice?

I’ve advised a number of companies pro bono on how to apply these ideas and have been more directly involved in 2 start-ups, BridgeBio and Roivant, as a seed investor and a director. I’m now in the process of talking with a number of stakeholders about possible financing structures that can make gene therapies more widely accessible. The hope is that we can get something in place in time to be used as a template for the many other gene therapies that are coming online.

: How enthusiastic are people about working with you and putting these ideas into practice?

I’m seeing tremendous enthusiasm from investors, drug manufacturers, and patients. There’s definitely money out there, waiting to be deployed and clearly a need for these new financing structures. Where we’re getting some hesitation—not so much pushback, but cautiousness&mdash;is among payers. State Medicaid plans don’t have an ability to amortize expenses; their budgets are set year to year and it’s not trivial for them to borrow funds or move expenses across budget years. As a result, they’re interested but more hesitant because they don’t really know what’s involved and they’ve got enough challenges to deal with currently. But given how many gene therapies are likely to be approved over the next few years, I suspect they’ll figure out a way to use these creative financing methods when the time comes.

Andrew W. Lo biography. MIT website. alo.mit.edu/biography/. Accessed October 19, 2018.

Das S, Rousseau R, Adamson PC, Lo AW. New business models to accelerate innovation in pediatric oncology therapeutics: a review. 

. 2018;4(9):1274-1280. doi: 10.1001/jamaoncol.2018.1739.

Das S. Rousseau R, Adamson PC, Lo AW. The challenge of pediatric oncology: new business models to accelerate innovation. 

. 2018;36(suppl 15). ascopubs.org/doi/abs/10.1200/JCO.2018.36.15_suppl.10528.

Evidence-Based OncologyTM sat down with Andrew W. Lo, PhD, to discuss his proposals to increase investment in medical innovation and utilization by giving investors more ways to support both research organizations and individual patients.

Renting Health vs Buying Cures: How New Financing Tools Can Boost Cancer Therapy Development

LARGE CARDIOVASCULAR OUTCOMES trials (CVOTs), designed to show how new diabetes medications afect the incidences of cardiovascular (CV) death, heart attacks, and strokes, also provide limited insight into another area: microvascular complications, such as renal neuropathy and retinopathy.

The data, however, do not tell a consistent story. Glucagon-like peptide 1 (GLP-1) receptor agonists may reduce the overall risk of kidney problems, but at least 1 medication in the class was associated with proliferative retinopathy progression in trial patients. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, on the other hand, appear to reduce the overall risk of kidney problems more than any of the GLP-1 agonists, all without any reported short-term efect on retinopathy. However, the SGLT2 inhibitor, canaglifozin—but no other drug from this class to date&mdash;is associated with a higher risk of amputation compared with placebo, although overall rates were small. As for dipeptidyl peptidase-4 (DPP-4) inhibitors, there’s no evidence that they have any particular infuence on any microvascular outcome (although these outcomes were not rigorously evaluated with these agents in CVOTs).

The strength for all of these vascular fndings is far from conclusive, but according to John B. Buse, MD, PhD, there’s more evidence of renal protection, particularly for the SGLT2 inhibitors, than damage elsewhere. The ease of measuring creatinine levels ensures that most CVOTs collect regular data on every patient’s kidney function, but no CVOT has regularly measured circulation to the eyes and extremities, so the outcome data have come from the very few patients whose adverse events required surgical procedures.

“The CVOTs to date haven’t made any efort to systematically measure neuropathy or retinopathy in all patients, and there just aren’t enough surgeries to use them as proxies. I suspect the association between some drugs and increased surgeries may stem from the suddenness with which they lower blood sugar,” said Buse, a distinguished professor at the University of North Carolina (UNC) School of Medicine who has participated in several CVOTs. “Previous work has shown that fasting blood sugar reductions can exacerbate preexisting eye problems, even though lower blood sugar reduces long-term complications, so doctors might want to take the precaution of starting small and gradually increasing the dose, particularly in poorly controlled patients who already have eye damage. For patients with clinical CV disease, the benefts on heart attack, stroke, and CV death far exceeds these small risks.

“The evidence on kidney function is much more robust, and it shows that both GLP-1 agonists and SGLT2 inhibitors tend to improve outcomes. That said, the fndings are not yet strong enough that they should be a major consideration in drug selection,” said Buse, who is also the chief of UNC Health Care’s Division of Endocrinology and head of its diabetes center. “The main consideration is still what it has always been: getting the patient’s A1C [glycated hemoglobin] to target levels of blood sugar control with whatever combination of medications works best for each patient.”

The LEADER trial, which randomized 9340 patients between liraglutide (Victoza) and placebo and followed them for a median period of 3.8 years, made headlines by finding that the GLP-1 analogue was associated with lower rates of stroke, myocardial infarction, and CV death. Less publicized was the fact that liraglutide use was associated with a signifcant reduction in nephropathy events, which were defned as “a new onset of persistent macroalbuminuria or persistent doubling of serum creatinine level and creatinine clearance per MDRD<45 mL/min/1.73m

[Modifcation of Diet in Renal Disease Study equation] or the need for continuous renal-replacement therapy (in the absence of an acute reversible cause) or death due to renal disease.” There were 1.5 such events per 100 patient-years in the liraglutide group and 1.9 per 100 patient-years in the placebo group (HR, 0.78; 95% CI, 0.67-0.92; P = .003). There was no signifcant diference in retinopathy between the 2 groups and no specifc attempt to measure neuropathy by amputations or other vascular outcomes.

The SUSTAIN-6 trial, which randomized 3297 patients among placebo and 2 doses of semaglutide (a longer-acting version of liraglutide), found that the GLP-1 agonist resulted in signifcantly less nephropathy than placebo (defned as in the LEADER trial) and signifcantly more proliferative retinopathy progression (defined as “the need for retinal photocoagulation or treatment with intravitreal agents or vitreous hemorrhage or diabetes-related blindness). Neuropathy events were detected in 62 semaglutide patients and 100 placebo patients (HR, 0.64; 95% CI, 0.46-0.88; P = .005). Retinopathy was detected in 50 semaglutide patients and 26 placebo patients (HR, 1.76; 95% CI, 1.11-2.78; P = .02).

The ELIXA trial, which randomized 6068 patients between lixisenatide (Adlyxin) and placebo, found that the albumin/creatine ratio in urine samples rose 26% in lixisenatide users (to 11.9 mg/g) and 32% in placebo users (to 13.4 mg/g). Renal and urinary adverse events were also found in fewer lixisenatide patients (12) than placebo patients (20). Neither result rose to the level of signifcance, however, and there were no data on retinopathy or neuropathy.

The EXSCEL trial, which randomized 14,752 patients between weekly exenatide (Byetta) and placebo, did not report any microvascular data in the main paper.

The EMPA-REG OUTCOME trial, which randomized 7020 patients among 2 doses of the SGLT2 inhibitor, empaglifozin (Jardiance), and placebo, also found evidence of CV beneft, but the initial write-up provided no signifcant microvascular data. The rate of kidney failure was lower in empaglifozin users than in the placebo group (5.2% vs 6.6%, respectively), but the diference was not signifcant. The study did not publish any comparative data related to neuropathy or retinopathy.

The CANVAS program, which followed 10,142 patients who were randomized between canaglifozin (Invokana) and placebo for a mean period of more than 3 years, also found better renal outcomes in the canaglifozin group than in the placebo group. There was a 40% reduction in combined endpoint of estimated glomerular fltration rate, the need for renal-replacement therapy, or death from renal causes (HR of canaglifozin was signifcantly associated with increased risk of lower extremity amputation. There were 6.3 amputations (mostly toes or metatarsals) per 1000 patient-years in the canaglifozin group and 3.4 amputations per 1000 patient-years in the placebo group (HR, 1.97; 95% CI, 1.41-2.75).

The EXAMINE trial, which followed 5380 patients randomized between alogliptin (Nesina) and placebo, tracked kidney function over a median period of 18 months and found no signifcant diference between the 2 arms. The study paper did not disclose any data about retinopathy or neuropathy.

The SAVOR-TIMI-53 trial, which randomized 16,492 patients between saxagliptin and placebo, did not reveal meaningful diferences in signifcant renal events. The study authors did not disclose data on less serious kidney problems or on neuropathy or retinopathy.

The TECOS trial, which randomized 14,671 patients between sitagliptin (Januvia) and placebo, reported on several types of microvascular outcomes but found little diference between the medication and placebo. Renal failure occurred in 1.4% (100) of sitagliptin patients and 1.5% (111) of placebo patients, which was not a signifcant diference. Similar numbers of sitagliptin and placebo patients also experienced peripheral arterial disease (2.7% [197] vs 2.9% [209]), amputation (0.8% [60] vs 0.9% [66]), diabetic neuropathy (4.1% [303 vs 3.8% [281]), diabetic blindness (0.3% [24] vs 0.3% [25]), and retinopathy (2.8% [205] vs 2.2% [158]).

Physicians should have more microvascular outcome data to guide their decisions. Another major CVOT, the DECLARE-TIMI-58 trial of dapaglifozin (Farxiga), is expected to report results in 2019. Researchers, moreover, are mining the huge amounts of data generated by existing CVOTs to find additional results. All of the initial papers focused very heavily on the CV outcomes such trials are designed to measure.)

Researchers have already mined data from the EMPA-REG trial for more information about empaglifozin and renal function, and they have found that SGLT2 inhibitor use is associated with slower progression of kidney disease and fewer renal events. New or worsening nephropathy occurred in 525 of 4124 (12.7%) empaglifozin patients and 388 of 2061 (18.8%) placebo patients (HR, 0.61; 95% CI, 0.53-0.70; P <.001).

“The renal outcomes analysis from EMPA-REG evaluated several measures of renal disease progression and found that empaglifozin use was consistently associated with relative risk reduction in important renal events of approximately 40%. Analysis of canaglifozin data from the CANVAS program produced similar fndings. Although these studies were not specifcally designed to evaluate chronic kidney disease [CKD] progression as a primary outcome (most patients in these trials did not have signifcant CKD at baseline), these results are still pretty compelling,” said Mikhail Kosiborod, MD, a professor of medicine at Saint Luke’s Mid America Heart Institute and University of Missouri-Kansas City School of Medicine, who was not involved in either EMPA-REG or CANVAS, but is participating in other CVOTs of antidiabetic agents.

“All other things being equal, these fndings suggest that, clinically, one might consider an SGLT2 inhibitor for a patient with evidence of early diabetic nephropathy. More data will be generated on this very topic in the next few years, with several dedicated large clinical trial programs currently evaluating the efects of various SGLT2 [inhibitors] on renal outcomes in patients with CKD, regardless of diabetes status.”

Other research teams are working to combine data from various trials to perform meta-analyses. The hope, as always, is that truly giant patient populations will create the statistical power needed to reach fndings that go beyond the scope of the individual studies.

Better still, the makers of empaglifozin and dapaglifozin have already begun new trials in patients with CKD. The frst of the trials will have 5000 patients

The CREDENCE trial of canaglifozin’s renal outcomes, moreover, has already been going on for several years.

There will be limits, however, to the ability of all of this research to answer questions about microvascular outcomes. Many of the trials that are available for researchers to analyze simply did not collect much data on neuropathy or retinopathy, and CVOT patients, depending on the trial, may not be refective of patients with type 2 diabetes as a whole. Most of them have longstanding and poorly controlled disease that has already led to a CV event, and although their microvascular profles may be more representative, there’s no guarantee that their outcomes will mirror those of other patients.

Despite these limitations, physicians have little reason to expect more robust microvascular data anytime soon. Trials specifcally designed to discover how new drugs afect neuropathy and retinopathy seem unlikely. The Diabetes Control and Complications Trial took 10 years to demonstrate the microvascular benefts of a 2 percentage point reduction of A1C levels (in patients with type 1 diabetes).

Establishing the beneft, if any, of lesser reductions associated with the use of new medications would likely take longer and cost more, even if the specifc effects of those medications improved outcomes by means other than blood sugar reduction, Buse said.

Efforts to mine real-world data can help, but have their own limitations. Coding errors can occur with microvascular outcomes, which may impact the findings. If patients switch medications frequently, as patients with diabetes do, this may complicate interpretation of the results. Even in places like the United Kingdom or Denmark, where most citizens are publicly insured and limited formularies minimize drug switching, it’s hard for retrospective analyses to provide a high degree of certainty for microvascular events.

1. Marso SP, Daniels GH, Brown-Frandsen K, et al; LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. 

. 2016;375(4):311-322. doi: 10.1056/ NEJMoa1603827.

2. Marso SP, Bain SC, Consoli A, et al; SUSTAIN-6 Investigators. Semaglutide and cardiovascular outcomes in type 2 diabetes. 

. 2016;375(19):1834-1844. doi: 10.1056/NEJMoa1607141.

3. Pfeffer MA, Claggett B, Diaz R, et al; ELIXA Investigators. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. 

. 2015;373(23):2247-2257. doi: 10.1056/NEJMoa1509225.

4. Holman RR, Bethel MA, Mentz RJ, et al; EXSCEL Study Group. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. 

. 2017;377(13):1228-1239. doi: 10.1056/NEJMoa1612917.

5. Zinman B, Wanner C, Lachin JM, et al; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. 

. 2015;373(22):2117-2128. doi: 10.1056/NEJMoa1504720.

6. Neal B, Perkovic V, Mahaffey KW, et al; CANVAS Program Collaborative Group. Canagliflozin and cardiovascular and renal events in type 2 diabetes. 

. 2017;377(7):644-657. doi: 10.1056/NEJMoa1611925.

7. White WB, Cannon CP, Heller SR, et al; EXAMINE Investigators. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. 

. 2013;369(14):1327-1335. doi: 10.1056/NEJMoa1305889.

8. Scirica BM, Bhatt DL, Braunwald E, et al; SAVOR-TIMI-53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. 

. 2013;369(14):1317-1326. doi: 10.1056/NEJMoa1307684.

9. Green JB, Bethel MA, Armstrong PW, et al; TECOS Study Group. Effects of sitagliptin on cardiovascular outcomes in type 2 diabetes. 

. 2015;373(3):232-242. doi: 10.1056/NEJMoa1501352.

10. Wanner C, Inzucchi SE, Lachin JM, et al; EMPA-REG OUTCOME Investigators. Empagliflozin and progression of kidney disease in type 2 diabetes. 

. 2016;375(4):323-334. doi: 10.1056/NEJMoa1515920.

11. AstraZeneca announces two new phase IIIb trials for Farxiga in chronic kidney disease and chronic heart failure [press release]. Cambridge, UK: AstraZeneca; September 12, 2016. astrazeneca.com/media-centre/press-releases/2016/astrazeneca-announces-two-new-phase-IIIb-trials-for-Forxiga-in-chronic-kidney-disease-and-chronic-heart-failure-120920161.html. Accessed November 27, 2017.

12. Empagliflozin (Jardiance) to be studied in chronic kidney disease [press release]. Ingelheim, Germany, and Indianapolis, IN: Boehringer Ingelheim; June 12, 2017.

https://www.boehringer-ingelheim.com/press-release/empagliflozin-be-studied-chronic-kidney-disease. Accessed November 27, 2017.

13. Evaluation of the effects of canagliflozin on renal and cardiovascular outcomes in participants with diabetic nephropathy (CREDENCE). clinicaltrials. gov/ct2/show/NCT02065791. Updated August 28, 2017. Accessed November 27, 2017.

14. Nathan DM; DCCT/EDIC Research Group. The diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: overview. 

. 2014;37(1):9-16. doi: 10.2337/dc13-2112.

Evidence is more robust on kidney function but not sufficient to make drug decisions, one expert said. A whole separate trial, called CREDENCE, is examining renal function in patients taking canagliflozin.

As Trials Report Cardiovascular Outcomes Data, What About Microvascular Results?

When UnitedHealthcare (UHC) announced in May 2016 that it would only cover insulin pumps made by Medtronic for most adults, patient advocates decried the news as both a major loss for those affected and, quite possibly, a harbinger of a world where exclusivity pacts stifled competitive innovation. Investors, it seemed, were in full agreement. Shares of smaller pump maker Tandem Diabetes Care immediately dropped 20% when news of the deal became public.

  Such predictions, however, may prove overly dramatic. The past 16 months have seen Medtronic sign an outcomes-based payment agreement with another insurer, but no insurer has followed UHC’s lead and signed exclusivity pacts with Medtronic or any other pump maker. If UHC patients are protesting the policy, they have been less visible in recent months. The exclusivity deal helped inspire a campaign by JDRF (formerly the Juvenile Diabetes Research Foundation),

  As for the deal’s impact on UHC patients, outsiders are forced to guess. UHC has declined to disclose any figures related to the policy: how many of its policyholders use insulin pumps, what pumps they chose before the transition, or how many have switched to Medtronic after preferred pumps broke or were out of warranty. An estimated 1.25 million

 (0.4%) of the nation’s 325 million people

 have type 1 diabetes (T1D). Estimates of the percentage of American patients with T1D who use a pump vary, but the JDRF currently reports the figure at 40%.

 Roughly 75% of all pump users have a Medtronic pump. The vast majority have T1D, although a very small number have type 2 diabetes.

  Still, it’s hard to get a precise handle on the number of patients affected by the UHC decision, since the policy excludes Medicare Advantage patients, those younger than 18, and enrollees of UHC Sierra Life and Life Commercial.

 Based on UHC’s combined commercial and Medicaid population of 36.5 million, the number of people who might be asked to switch pumps is likely between 10,000 and 12,000.

Eventually, nearly all adult Medicaid and commercial UHC patients who refuse to buy other pump brands out-of-pocket will have to switch, either to a Medtronic pump or to insulin injections. Those who used their benefits to buy a non-Medtronic pump before the policy took effect can still get coverage for supplies so long as the pump keeps working and remains under warranty. Warranties typically last 4 years, so the transition probably has yet to affect more than one-third of UHC patients who prefer non-Medtronic pumps.   Such numbers only tell part of the story. It is impossible to know the strength of patient preferences overall and for individual patients.

Michele Hynes, who is covered by UHC, switched from Medtronic to Animas more than 4 years ago because the Animas pump was waterproof (as some Medtronic models now are) and because it had a remote control. “As a woman, I often don’t have access to pockets if I am wearing a skirt or dress. As such, in these cases, I generally clip my pump to my bra. It is SO convenient to be able to dose from my meter and not have to leave the table or grab my pump out of my bra,” she wrote to 

An even bigger deal for Hynes is the sensor. The 41-year-old mother of 2 young children wants an integrated system that automatically delivers insulin based on readings from a continuous glucose monitor (CGM), but she wants a system that works with a Dexcom sensor. If she moved to a Medtronic pump, the only way to automate delivery would be to move to a Medtronic sensor as well.  

“In general, I have found that anyone who has used Dexcom is less than impressed with Medtronic sensors. And as such, I am hesitant to switch—to the point I am still using an out-of-warranty Animas pump,” she wrote. “I will probably concede defeat and order a new pump in the next 2 months.”

Looking beyond patient preferences, the other important metrics for evaluating the policy are, obviously, health outcomes, total cost savings, and how any savings are distributed among UHC, premium payers, and pump-using patients. UHC, again, declined to disclose any details.  

“Patient safety, service, and cost were key considerations in our decision-making process to partner with Medtronic,” wrote UHC spokeswoman Kristen A. Hellmer in an emailed response to 

™ to requests for specific numbers. “We have finalized a value-based agreement, which rewards improved outcomes for UnitedHealthcare members on insulin pumps and places greater focus on quality rather than the volume of care delivered.”  

Some observers have argued that patients might suffer worse outcomes after being pushed away from first-choice machines and toward devices they found less intuitive or less suited to their needs,

 but there’s no trial data connecting current Medtronic pumps to inferior outcomes. There is, on the other hand, solid evidence tying Medtronic’s most advanced pump system to superior outcomes.  

Medtronic’s MiniMed 670G, the first system to receive the FDA designation of “artificial pancreas,”

became available to US patients in June. It combines a pump with a CGM and software to automate many dosing decisions. Even in manual mode, it automatically suspends insulin delivery when blood glucose levels fall dangerously low (and resume it when they rise). In auto mode, the system uses CGM readings to adjust insulin delivery levels every 60 seconds. It’s nowhere near perfect, but trial data strongly suggest that the automation—which is unique to Medtronic’s system&mdash;significantly improves outcomes. Among 124 patients in a 3-month trial, auto mode reduced the following: average glycated hemoglobin (A1C) from 7.4% to 6.9%, dangerous hypoglycemia by 40%, and reduced time spent with excessive blood glucose by 11%.

“Although we are in favor of more, rather than less, patient choice, there’s good reason to believe that this UnitedHealthcare policy doesn’t change that much negatively. It’s likely that most UnitedHealthcare pumpers already use Medtronic, that those pumpers will be among the earlier ones to upgrade, and that outcomes will be as good or better with most that are in line to shift from another brand. Medtronic has shown that this product will improve outcomes, that’s what matters to payers in this era of value-based healthcare, and there’s good reason to think that UHC’s policy will deliver on outcomes,” said diaTribe Foundation founder Kelly L. Close, who advised patients who don’t want Medtronic to raise their voices, especially on social media.

“Assuming it’s true that Medtronic systems improve outcomes, the question would then become, which is more important: patient choice or better outcomes? The math would say better outcomes, but I also doubt that deep down, Medtronic or UnitedHealthcare wants this controversy,” Close said in an interview.   There is no definitive proof that the 670G produces superior results in real-world settings.

Obviously, Medtronic has not had time to complete a postmarketing study required by the FDA. Until it does, the only indicator of efficacy comes via anecdotes from early adopters and testers, which have generally been positive. Close spends much of her time talking to people about medical devices for T1D, and she says she rarely hears a negative review from anyone who has lived with the 670G. Even the people who are nervous about surrendering dosing control to an algorithm, people who are predisposed to be cautious about turning control over to a system, or even to dislike the system, usually end up telling her that it doses them better than they can dose themselves.  

Medtronic, moreover, appears confident that the 670G will improve real-world outcomes and save money for payers. In June, Medtronic announced a deal with Aetna that ties payment rates for its systems to the results those systems produce in patients who switch over from insulin injections.

 The companies declined to disclose the financial details of the deal, but Medtronic said that the achievement of A1C targets will be the first metric used to determine payments. Other metrics, such as reductions of hypoglycemic episodes, could be added later.

“This agreement is an important first step as we look to broadening our partnership to facilitate patient access to the most advanced diabetes management solutions across the care continuum that not only ensure outcomes, but lower the overall cost of care for this chronic and burdensome disease,” said Suzanne Winter, vice president of the company’s Americas Diabetes Group, in the press release that announced the deal.

“We recognize the important role that health plans make in coverage, affordability, and choice for type 1 diabetes therapies,” wrote JDRF spokesman Christopher Rucas in an email about the group’s opposition to exclusivity deals. “We have put together a campaign we’re calling Coverage2Control, which will call on insurance companies to provide members with diabetes 3 things to give them control.”  

  1. Predictable and reasonable out-of-pocket costs for insulin and diabetes management tools.

  2. Freedom to choose an insulin pump that makes sense for the individual, which means no exclusive agreements with pump makers that limit choice.

  3. Coverage of all life-saving devices, including artificial pancreas technology.

Rucas said the JDRF is “engaging directly with health plans, but also wants to provide the T1D community with opportunities to take action.” The JDRF and other patient advocates believe that widespread coverage for all FDA-approved pumps benefits patients not only by letting them choose whatever current machine works best for them, but also by spreading revenue enough to encourage competition and innovation. There is a widespread belief among both patient advocates and financial analysts that at least 1 smaller player, possibly more, could soon drop out of the market.

Tandem Diabetes Care lost nearly $24 million in the first quarter of 2017 as pump shipments fell 30% to 2816.

 The company lost more than $83 million in 2016 and more than $72 million in 2015.

 Johnson & Johnson has said it is considering selling its diabetes care business, including Animas, a pump-making subsidiary that’s based in suburban Philadelphia.

This comes after the Animas deal won FDA approval in December 2016 for the OneTouch Vibe insulin pump, the first to integrate with the Dexcom G5 CGM.

 Also in the mix is Insulet, which has struggled to convince Medicare to offer reimbursement for its tubeless Omnipod pump.

 And in August, the remaining patients using pumps from Roche Diabetes Care were turned over to Medtronic for ongoing support after Roche announced plans to stop selling its Accu-Chek pumps in the United States.

Such a situation would not be historically unique. The number of pump makers has waxed and waned considerably over the past 40 years. New entrants have kept coming in with new technology, trying to dethrone MiniMed, the dominant player purchased by Medtronic for $3.7 billion in 2001.

 None have succeeded, but their efforts have helped fuel a steady improvement in pump technology. Pumps have gotten considerably smaller, more discrete, smarter, easier to use, and more reliable since they first appeared in the 1970s.

   There is reason to believe that more players will enter the market with new ideas. For example, Bigfoot Biomedical is performing clinical trials on a system that includes a pump that has no controls on its body because it is controlled through a smart phone app.

Even if fewer new companies enter the market and the pace of traditional pump development slows, patients will see differences. Today’s models are good enough that observers like Close see little need for dramatic hardware improvement, regardless of how competitive the pump market is. Mechanical improvement will continue, she thinks, but more of the value will come from the brains of the pump.

“Insulin is an incredibly dangerous drug, and a machine will always figure out dosing better than patients or parents or partners. Automation is where we’re going, and it’s all about the algorithms and who can make the easiest-to-use systems—take away steps, make things easier to use and smarter. That could come from the largest pump manufacturer, but it doesn’t necessarily have to. It can come from another company or academic or even hobbyist who wants to write it,” said Close, who gave the interview while testing a system that used software written by 1 individual to control her insulin.

“I can’t wait to try the 670G, and I can’t wait until it’s widely available. For now, having a smart algorithm in a box that costs $126 and keeps me between 80 and 120 all night every night is pretty excellent. Medtronic raised the bar with its new pump and the outcomes that they have proven (mainly less hypoglcyemia)—and they shouldn’t, and won’t, take their eye off the ball because the field will keep raising the bar ever higher.”

	1. Lawrence S. Tandem off 20% as it loses insurer to Medtronic for insulin pumps. Fierce Biotech website. http://www.fiercebiotech.com/medical-devices/tandemoff-20-as-it-loses-insurer-to-medtronic-for-insulin-pumps. Published May 3, 2016. Accessed August 20, 2017.

	2. JDRF launches “Coverage2Control,” a campaign to urge insurance companies to provide coverage that works for the type 1 diabetes community [press release]. New York, NY: JDRF; May 23, 2017. http://www.jdrf.org/press-releases/jdrf-launches-coverage2control-campaign-urge-insurance-companies-provide-coverage-works-type-1-diabetes-community/. Accessed August 201, 2017.

	3. Type 1 diabetes facts. JDRF website. http://www.jdrf.org/about/fact-sheets/type-1-diabetes-facts/. Accessed August 20, 2017.

	4. US Census Bureau. US and world population clock. https://www.census.gov/popclock/. Accessed August 29, 2017.

	5. UK still trails Europe and the USA on providing insulin pumps for type 1 diabetes. JDRF website. https://jdrf.org.uk/news/uk-still-trails-europe-usa-providing-insulinpumps-type-1-diabetes/. Published April 5, 2016. Accessed August 20, 2016.

	6. Idlebrook C. A look into Medtronic’s game plan. Insulin Nation website. http://insulinnation.com/treatment/a-look-into-medtronics-pump-game-plan/. Published August 19, 2016. Updated August 22, 2016. Accessed August 20, 2017.

	7. UnitedHealthcare. Network Bulletin, May 2016. UHC website. https://www.unitedhealthcareonline.com/ccmcontent/ProviderII/UHC/en-S/Assets/ProviderStaticFiles/ProviderStaticFilesPdf/News/May-Network-Bulletin_PCA-1-001514-04052016_R5.pdf. Published May 1, 2016. Accessed August 28, 2017.

	8. UnitedHealth Group website. Webcast replay: medical members, 2016. UHC Group website. http://www.unitedhealthgroup.com/Investors.aspx#close. Published

UnitedHealthcare has not released numbers on how many patients are affected by its exclusivity deal with Medtronic. While the initial press stories criticizing the transaction have died down, a JDRF initiative calls on insurers to preserve patient choice.

Andrew Smith

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