Did fenofibrate – a common cholesterol drug – reverse one 19-year old woman’s newly diagnosed Type 1 diabetes?
This is the question at the heart of a tantalizing medical mystery from Denmark. A study, recently published in the journal Case Reports in Medicine, tells of a single patient that achieved insulin independence shortly after diagnosis with Type 1 diabetes. One week after learning of her new condition, the young woman began a course of fenofibrate. Her insulin requirements dropped quickly and dramatically, and twenty days later she had reduced her daily use from 30 units to zero. Today, nearly two years later, she’s still going strong, enjoying effortless and healthy blood sugar levels without insulin. It appears to be a very rare case of complete Type 1 diabetes remission. The hope is that her success will be replicable.
I got in touch with the lead researcher, Dr. Karsten Buschard, who was both elated at the patient’s recovery and cautious about its meaning: “A trial is necessary. Before that, we have no scientific proof.”
If you’re wondering whether or not the young woman ever really had Type 1 diabetes to begin with, Dr. Buschard brushes aside the idea: “There is no doubt about that.” The patient was initially diagnosed in a state of diabetic ketoacidosis, blood sugar as high as 550 mg/dl, and with an A1c of 13.5%, displaying the classic symptoms of acute hyperglycemia. She additionally tested positive for two types of Type 1 antibodies.
Stories of robust honeymoon phases are not at all unknown, and various studies have found that a certain small percentage of patients newly diagnosed with Type 1 diabetes will experience honeymoons phases strong enough to resemble partial or complete remission lasting as long as a year. It is possible that she coincidentally enjoyed a tremendous honeymoon effect while on her experimental treatment. What makes this story remarkable – and perhaps less likely to represent a fluke occurrence – is the story of how and why the doctors decided to try fenofibrate.
It starts with Dr. Buschard’s team of Danish researchers. In a 2018 paper, his team showed that fenofibrate could completely prevent the development of diabetes in NOD mice, animals that have been bred to spontaneously develop diabetes as they age. Fenofibrate furthermore reversed the diabetes in half of the mice that had already developed the condition.
Promising news, perhaps, but mice are not men, and the scientific literature is cluttered with many cures for rodent diabetes that did not work on human patients. The paper, titled “Abnormal islet sphingolipid metabolism in type 1 diabetes,” was not the kind of eye-catching work likely to interest the general public. It was obscure and highly technical, difficult for a layman to interpret, and of apparently limited relevance to anyone but other researchers. It would have been unreasonable to expect that Dr. Buschard had hit upon a treatment that might have immediate applicability among us humans.
But somehow or other, Dr. Buschard’s recently-published paper came to the attention of the father of a teen newly diagnosed with Type 1 diabetes. He quickly established a correspondence with Dr. Buschard, and they discussed a plan to try the fenofibrate with his daughter. Fenofibrate, also sold under the brand names Fenoglide, Tricor and Triglide, is most commonly prescribed to treat high cholesterol, especially high triglycerides. It’s considered to have relatively few side effects, and has been well tolerated by people with diabetes in the past. There seemed to be nothing to lose.
The family’s commitment to this hail mary pass of a medical treatment – Dr. Buschard characterized the father as “a man taking action!” – is underscored by the fact that fenofibrate was not actually available in their home country of Denmark. They crossed the border south to Flensburg, the northernmost city in Germany, to fill the prescription. For Dr. Buschard, it was a rare opportunity to see his work put into immediate practice: “It was exciting. And when we learned that she could cope without taking insulin, that was very exciting. It was exciting for the poor patient, the father, and for me of course.”
I have already summarized the results, which were remarkable. The young patient’s latest tested A1c was 5.7%. Her fasting C-peptide levels have normalized. Her concentration of autoantibodies has even declined. At publication, it had been “21 months since she took her last regular injection of insulin at day 19 after initiation of fenofibrate treatment. She stopped measuring her blood glucose daily after 410 days.”
As a medical miracle, the teenager’s case is almost, but not quite, unique. A review of the medical literature finds more than a few case studies of similarly profound Type 1 remission. Many of these studies also propose a plausible mechanism to explain the medical marvel (such as sitagliptin or immunosuppressants) that we can presume did not stand further scrutiny as an avenue for widespread use. Some are so inexplicable as to strain credulity. This case report from 2015 describes a 32-year old that ignored her condition and stopped taking insulin entirely, only to spontaneously improve (during a 7-month prison sentence!) from a 16.6% A1c to a 5.6%. One wonders if there was a case of mistaken identity.
But the case for fenofibrate is strengthened by the decades of hard work that Dr. Buschard put into understanding and revealing the mechanism by which it is theorized to work. The key is the molecule sulfatide, which Buschard calls “a chaperone for insulin,” a critical component to the beta cell’s work of forming and secreting insulin. “The main thing is that fenofibrate increases the amount of sulfatide, which seems to be a very important molecule in the life of the Beta cell.” Dr. Buschard’s own research indicated that patients with newly-diagnosed Type 1 diabetese have about 77% less sulfatide than healthy controls. If sulfatide could be upregulated back to healthy levels, maybe it could halt the progression of the disease.
That appears to be exactly what happened. The marvelous success in the teenager was welcome, but not totally unexpected: “I really hope and expect that it would work. Maybe not in 100% of patients, but maybe one-third of them, or half of them.” Nevertheless, he remains cautious about making bold claims: “It’s important for me to stress that there is no scientific proof. Good animal data, but we need to have final scientific proof. That’s how it is.”
When I asked Dr. Buschard if I should take fenofibrate, he said, “I would be astonished if you had the same effect.” He doesn’t think there is any likelihood that the drug would help much with any patient with longstanding diabetes. Indeed, many people with diabetes already take fenofibrate, not only for its cholesterol-lowering properties but also because it has been found to particularly benefit patients with diabetic retinopathy. Surely, if the drug had miraculous properties, it would have been noticed by now.
Dr. Buschard theorizes that swift application is essential to the success of the drug:
“It needs to be immediately after diagnosis. It should be set in before the T-cells are really active. When the T-cells are really active, it is no doubt too late. It should be started as soon as possible, and we are talking days, or a few weeks, not months.”
I asked him if he were ready for our article to prompt patients to request the drug from their doctors. The perils of inadequately tested drug recommendations have been much in the news lately, after all. He didn’t sound too worried, but he stresses that he is not actually recommending the drug for broad use at this time: “I’m a cautious doctor.” In particular, fenofibrate is less tested in children, and more study is needed before he would consider giving it to anyone under the age of 16.
The next step is to study the effects of the drug in a more rigorous manner. He has been active in organizing a trial to really put fenofibrate to the test: “We hope to have a trial, randomized and double blind, as good as it can be. We need it to come up as soon as possible.”
In the meantime, Dr. Buschard will continue to keep an eye on the teenager that seems to have reversed her Type 1 diabetes. She will continue to take fenofibrate for the foreseeable future.
“Is she cured? We don’t know. We don’t know the future for her. If it goes on, it will be fantastic.”
Reviewed by Mariela Glandt, MD.