Baricitinib: A Cure for Type I Diabetes?

Type I Diabetes requires demanding treatment through the injection of insulin into the body; however, a pre-existing drug, baricitinib, may reduce the need for insulin injections.

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By Stacey Chen

Imagine you smell the most delicious aroma coming from your local bakery, but before you step inside to indulge in a sweet, you need to check: is your blood sugar too low? Too high? If so, you cannot even think of trying that cinnamon roll in the window—otherwise, you would become thirsty, tired, and maybe even go numb. This is not an unusual problem to face as nearly nine million people around the world are diagnosed with type I diabetes, a chronic autoimmune disease where the pancreas—an organ that aids with digestion—makes little to no insulin because of a lack of insulin-producing cells.

Insulin is an important hormone that allows the body to absorb glucose, a carbohydrate found in the food we eat. Normally after eating food, insulin takes the glucose from the bloodstream and helps transform it into energy to help fuel the body. Without insulin, glucose remains in the bloodstream, causing high blood sugar and depriving cells of the energy they need. As a result, cellular structures that require energy to function—such as the heart, blood vessels, nerves, kidneys, or eyes—can become damaged over time.

Type I diabetes treatment often includes frequent blood sugar checks, carbohydrate counting, and—most importantly—insulin injections to ensure blood sugar stays under 140 mg/dL to avoid damage to the body. Insulin injections are made synthetically in a lab before being pumped into an injection tube and fulfill the same function as naturally generated insulin, allowing cells to absorb glucose from the bloodstream. These injections are self-administered into the veins 30 minutes before a diabetic eats a meal, three or more times a day, in order to allow the insulin to digest consumed food.

However, these injections require extreme time specificity, as administering insulin one to two hours after eating a meal could prevent it from having any effect on the body, with glucose staying in the bloodstream instead of being processed into energy. Furthermore, administering insulin too early before eating could cause a drop in blood sugar by dramatically decreasing the amount of glucose in the bloodstream. When glucose levels are too low, it can lead to cells becoming starved for energy since there is no substance to turn into fuel. As a result of the highly specific circumstances required to administer them, insulin injections can be a hassle for those with type I diabetes. In order to remedy this issue, researchers at St Vincent’s Institute of Medical Research performed a clinical trial to test baricitinib, a pre-existing drug that could eliminate the need for insulin injections by offering an alternative treatment for type I diabetes.   

Baricitinib is a medication commonly used for the management and treatment of rheumatoid arthritis, an autoimmune disease in which the immune system attacks healthy cells in the body, causing severe joint inflammation. Similar to how immune cells attack the joints in rheumatoid arthritis, immune cells destroy the pancreas’s insulin-producing beta cells in type I diabetes. Normally, these autoimmune reactions involve an enzyme, a protein that accelerates chemical reactions, called Janus Kinases (JAKs). JAKs help activate the immune system within the body through the activation of cytokine receptors, proteins that communicate signals to other immune cells in the body, and STAT proteins, which transmit immune signals to the rest of the body. Essentially, these proteins help activate the immune cells needed to destroy any detected foreign matter within the body.

Baricitinib is a reversible inhibitor of JAKs, meaning it can stop the activity of a JAK protein within the body. In the case of type I diabetes, this means that baricitinib may be able to prevent the body’s immune system from attacking these insulin-producing cells. If baricitinib is successful, the body would be able to stop the immune cells from destroying all the pancreas’s insulin-producing beta cells so that insulin could be created within the body. Fundamentally, baricitinib would allow the body to create the normal amount of insulin, essentially solving the symptoms at the heart of type I diabetes. 

Helen Thomas, an immunology research fellow at St Vincent’s Institute, tested the legitimacy of baricitinib in treating type I diabetes through a controlled study of 91 patients ranging from the age of 10 to 30. These patients were diagnosed with type I diabetes less than 100 days before the beginning of the trial, signaling that their bodies were still producing some insulin and that not all of their beta cells had been destroyed—if that were the case, they would have been diagnosed much earlier as a result of symptom presentation. Over a period of 11 months, 60 patients received four milligrams of baricitinib once a day, while 31 patients took a placebo pill daily. Every patient was instructed to reach a specific target HbA1c value, which indicates a person’s blood sugar over the course of three months. Essentially, if their body produced more insulin, they would inject less insulin to reach average blood sugar, while if they made less, they would inject more insulin to reach the target number. Moreover, these blood sugar values were monitored through a daily blood exam.

Researchers concluded that patients treated with baricitinib had higher levels of C-peptide, a byproduct protein released into the bloodstream alongside insulin by the pancreas. These results most likely indicate that the group that took baricitinib had more beta cell function within the body, therefore producing more insulin. Both groups had similar target HbA1c values as expected, but the baricitinib-treated group reached the target values without the need for any insulin injections.

While the baricitinib-treated patients continued to take baricitinib, three patients did not require any external insulin to maintain their blood sugar, and the remaining group members were able to slowly decrease the rate of their insulin doses, eventually requiring less over time. On the other hand, the placebo group needed to increase their insulin injections over time, indicating that they were producing less insulin organically and their type I diabetes was remaining constant. Once the patients in the experimental group cut their use of baricitinib, they required more doses to maintain normal insulin levels in the body. Therefore, it can be reasonable to conclude that though baricitinib is effective and has no unwanted side effects, it also needs to be taken continuously to keep working. 

Though there are some limitations to the trial—such as small sample size, limited age range, and the possibility of unknown side effects—the potential benefits are promising. Barticinib is more convenient than injecting insulin throughout the day, requiring only one pill each morning. Taking a pill also limits the possibility of injecting insulin outside of its effective time frame. Thus, baricitinib could be a promising first step in effectively treating type I diabetes without insulin injections.