Life After Islet Cell Therapy: What It’s Like To Take Immunosuppressants

Over the last 100 years, insulin and diabetes technology have transformed type 1 diabetes care. 

However, some people with type 1 experience unpredictable high and low blood sugar swings,  no matter how careful they are with their insulin regimen. Severe low blood sugar can be sudden and dangerous, and may render a person unconscious or unresponsive at moments of particular vulnerability, like while they are sleeping or driving.

For people who have trouble managing type 1 diabetes, the best option may be an islet cell transplant. 

What is islet cell therapy?

The goal of islet cell therapy is to replace beta cells that are absent or not functioning properly. Generally speaking, it is usually performed in people who have type 1 diabetes, and currently, the new islet cells come from a different person with a different genetic makeup. 

When someone with a functional pancreas dies, surgeons can remove the organ and then transplant either the whole organ or implant the insulin-producing islet cells in the pancreas into a person with type 1 diabetes. 

In many countries, both options are routine medical procedures, but in the U.S., islet cells isolated from a deceased donor are regulated by the FDA. Consequently, most forms of islet cell therapy are currently limited to Americans who participate in clinical trials.

Historically, these transplant procedures have been reserved for a very limited number of people for two reasons: First, there’s a limited supply of pancreases and islet cells from recently deceased donors, and second, living with a transplant requires careful management to ensure your immune system does not attack and reject the donor’s organ or insulin-producing islet cells.

Now, progress is being made. Vertex has recently demonstrated in a clinical trial that its lab-grown, stem cell-derived zimislecel (VX-880) islet cells can produce insulin just like deceased donor islet cells. In an ongoing trial, 10 participants with type 1 who received zimislecel no longer needed daily insulin after one year, though all required ongoing immunosuppressive therapy. The company’s results point the way towards a future in which there are no longer limits on the supply of these cells. 

How does the procedure work?

The most common method is to give the recipient the islet cells via an intravenous infusion into the hepatic portal vein of the liver. After preparing the cells, a minor surgery is performed to insert a catheter into the vein, where the transplanted cells will make a home for themselves.

The infusion is over fairly quickly, and the entire procedure is minimally invasive. Recipients receive a local anesthetic and a sedative, but do not require general anesthesia. The main risk involved is minor bleeding from the liver.

“Once the procedure is done, the catheter is removed, and it’s just a small band-aid on the skin,” said Dr. Piotr Witkowski, a transplant surgeon at the University of Chicago.

The new islet cells take a little bit of time to settle in and ramp up insulin production, but people who receive the therapy may be able to taper off their insulin treatment in the weeks following the surgery.

However, many people do not achieve complete insulin independence after the treatment and may require more infusions. In addition, the transplanted islet cells can become less effective at producing insulin over time. 

Researchers are not always certain why any given infusion of islet cells proves less effective than another. One reason could be that transplanted cells are of different quality, especially if they are being taken from donors who lived to different ages and led different lifestyles. The process of isolating the cells may also lead to different yields. Then, once the cells are in the recipient’s body, how long they last depends on factors like the recipient’s level of insulin resistance and the amount of immunosuppressants they are taking.

“We’re doing this dance where we don’t know what all the partners are,” said Peter Senior, an endocrinologist at the University of Alberta, about managing transplanted islet cells. 

Why does islet cell therapy require immunosuppression?

Although the procedure itself is simple, the preparation and follow-up are far more intensive. Right now, a person with type 1 diabetes receives islet cells that have someone else’s DNA. That means their immune system will try to eliminate them – unless the person takes immunosuppressants to tamp down their natural immune response.

Immunosuppressants are any drugs that suppress the immune system. Many people who have autoimmune diseases like rheumatoid arthritis, lupus, and psoriasis regularly take immunosuppressants. However, people with these types of chronic conditions usually need just enough of their medication to manage symptoms during flare-ups. When they are in remission, they can usually stay off the meds altogether.

In contrast, people who receive transplants generally need to commit to taking higher doses of immunosuppressants for the rest of their lives – or for at least as long as their transplants survive, anyway. 

Healthcare providers approach immunosuppression for islet cell therapy in the same way they would approach it for any other transplant procedure – albeit with lower doses than someone who is receiving something more intensive, like a bone marrow transplant, might receive. 

Treating with immunosuppressants also appears to protect the islet cells from the autoimmune response that caused type 1 diabetes in the first place, but there are many remaining questions. Dr. Melena Bellin, an endocrinologist at the University of Minnesota, explained that most people with type 1 diabetes who are currently eligible for islet cell therapy were diagnosed years or even decades before receiving the transplant procedure. 

“Their autoimmunity may not be as active as someone who’s just been diagnosed,” she said. “We don’t know how well our immunosuppression would control autoimmunity in those people.”

However, Senior pointed out that the immune system can be unpredictable, and the time since diagnosis does not necessarily tell you how active someone’s autoimmunity is at present.

“There might be situations where it might pop up again,” he said.

The truth is that researchers need to try islet cell therapy in more people to understand exactly how the immune system is responding to it. Until then, there’s a limit on how much they can experiment with immunosuppression to find the ideal dose that minimizes side effects without sacrificing effectiveness.

What is it like to take immunosuppressants for islet cell therapy?

The largest dose of immunosuppressants that a person receiving islet cell therapy will have to take comes in the days leading up to and following the procedure. When the new islet cells are first introduced, the immune system is more likely to launch an all-out attack, causing high levels of inflammation that can make a person feel really sick.

This large initial dose of immunosuppressants is one of the reasons that islet cell therapy is not an outpatient procedure. For the five days surrounding the procedure, Bellin said that the patients she works with will typically receive an infusion of anti-thymocyte globulin, a strong immunosuppression drug. Because this is a particularly vulnerable moment for the patient, care is taken to ensure that the person is fully vaccinated and does not have an active infection.

After a person is released from the hospital, they start taking the kinds of immunosuppressant medications that they will be on for the long haul. The most effective ones are calcineurin inhibitors (CNIs). However, these drugs also have a negative impact on a person’s kidney function and appear to damage beta islet cells over time.

Healthcare providers try to minimize the amount of CNIs any transplant recipient has to take by combining them with other, less toxic immunosuppressants, but currently available alternatives are usually not as effective at keeping transplanted cells alive.

The right combination of drugs and dosages will be different for everyone. In the first month after the procedure, people will be returning to the hospital multiple times a week for blood tests. Further out from the procedure, hospital trips become less frequent, but at least for the first few years, people who have received islet cell therapy will need to have monthly blood tests.

People who are taking immunosuppressants have a higher risk of getting sick and more trouble getting better. These drugs make people more susceptible not only to infections, but also to certain types of cancer. 

Consequently, people who have received a transplant must be more diligent about their checkups, and they cannot just shrug off cold symptoms – they have to keep their healthcare providers in the loop about their health and carefully respond to any changes. Other side effects of these medications may include:

• Acne and other skin or hair changes
• High blood pressure and high cholesterol
• Headaches and insomnia
• Fatigue

All of that being said, day-to-day life is not all that different for a person who is taking immunosuppressants. Senior noted that many people think they will be wearing a hazmat suit for the rest of their lives, but in reality, it’s more like post-vaccine COVID-19.

“If you’ve got friends and neighbors who are sick and coughing and sneezing, maybe don’t go and hang out with them. Or, wear a mask, wash your hands, and those things really work very, very well,” he said.

As of June 2025, Senior and the team at the University of Alberta have administered islet cell therapy to 330 patients. In total, more than 2,500 people around the world have undergone the procedure following the particular protocol that was first established in Alberta in 1999. 

“We’ve got people who are elementary school teachers, kindergarten teachers, doctors, lawyers, nurses,” he said. “They all go back to work.”

Perhaps most importantly, Senior said that there can be leeway with immunosuppressants if a person’s health needs change.

“The hierarchy is: You’re alive, your kidneys are alive, and, three, the islets are alive,” he said. In terms of immunosuppressants, “it’s just not this one-size-fits-all ‘thou shalt take these forever no matter what the cost.’ That’s not how we roll.”

What does the future of immunosuppressants for islet cell therapy look like?

Although life on immunosuppressants is manageable, they carry side effects and require the person taking them to put a lot of time and energy into monitoring their health. So, researchers are always looking for new ways to keep the immune system from attacking transplants.

There are already some newer immunosuppressants available, and others could be on the way. Witkowski is currently running a trial testing the effectiveness of tegoprubart, an investigational antibody drug, which appears to be less toxic than other medicines and can be administered less frequently. 

Witkowski also wonders if many people could get by with lower doses of the immunosuppressants that are currently available. He pointed out that transplant recipients have been able to cut back on immunosuppressants during infections and still retain their islet cells. 

Researchers also continue to explore options that would eliminate the need for immunosuppressants. Recently, scientists used gene editing tools to modify donor-derived islet cells, cloaking them from the recipient’s immune system. They demonstrated that the edited cells could survive in the body of a person with type 1 diabetes for six months and produce insulin, even though that person was not taking immunosuppressants.

Other researchers are working on different approaches for making immunosuppressants unnecessary, and Witkowski hopes to see one or more of them crack the code in the not-too-distant future.

“As a first step, I do believe that less toxic immunosuppression will be the solution until we sort out how we can completely avoid immunosuppression,” he said.

The bottom line

Islet cell therapy has helped people with type 1 diabetes live their lives without the fear of severe, unpredictable changes in blood sugar. For these people, successfully managing transplanted islet cells with immunosuppressants may be a better option than unsuccessfully managing diabetes with insulin.

With stem cell-derived islet cells moving closer to becoming an approved treatment option, it seems plausible that more people with diabetes will have the option to try the therapy in the future. At the moment, for the few who have the option, deciding to get the procedure requires weighing the risks and benefits of long-term immunosuppressant therapy. 

Those who opt for the procedure typically find that they can continue to live the lives they want, provided they take the necessary precautions to manage their health. However, researchers continue to develop and test new medications that they hope will make immunosuppression easier to manage and make islet cell therapy available for more people.

Learn more about islet cell therapy here:

• First FDA-Approved Islet Cell Transplant Performed
• Clinical Trial Tests Cell Therapy To Cure People With Type 1 Diabetes
• When You Don’t Know You’re Low – Hypoglycemia Unawareness 101

This educational article was made possible through the support of Vertex Pharmaceuticals. diaTribe maintains final editorial discretion.