Levicure is a startup which is currently raising money to fund a phase-II trial for a combination therapy designed to prevent or delay T1D if given during the honeymoon period. This blog posting is reporting on the results of their retrospective phase-I clinical trial. That trial has already been completed and is motivating them to move forward with a larger phase-II trial.
The combination therapy used three medicines: GABA, Sitagliptin or Saxagliptin (which are dipeptidyl peptidase-4 inhibitors), and Omeprazole (a proton pump inhibitor). All three of these drugs are available now, and all have some evidence that they will help people with diabetes. They have all been tested (in some cases in combination with other medicines and each other). However, I think this is the first clinical trial that has reported on these three together.
The Study
This was a retrospective study, where the researchers reviewed the medical records of people who had been treated with the three drugs. The people were given the three drugs because their doctors thought it was the right treatment for them, not because they were enrolled in a trial. There is no randomization process and no control group. The trial size is determined by how many people got all three treatments in the time period the researchers looked at.
The researchers ended up with 19 people. Ten of them had received the three drugs during the first year after diagnosis (their honeymoon period). Nine more had received the drugs after that, so they had established T1D. The two groups were analyzed separately.
Results
The group (ten people) that started therapy during their honeymoon phase, called "early therapy" below had a statistically significant rise in C-Peptide production. The average went from just over 200 pmol/L to just under 500. Since the average for a person without T1D is at least 365, this is an important difference, as the change is from an abnormal result to a normal one. (All of these are fasting numbers.)
The group (nine people) that started the treatment more than a year after the onset of T1D did not show an improvement in their C-Peptide number, and none of them was able to stop injecting insulin. They did show improvements in treating T1D (using less insulin, having better A1c numbers, etc.)
Company: https://www.levicure.com/
History: https://healthtransformer.co/levicure-is-developing-a-breakthrough-triple-therapy-for-type-1-diabetes-b6c521e6b2c5
Clinical Trial Report: https://www.frontiersin.org/articles/10.3389/fendo.2023.1171886/full
Animal Testing: https://www.frontiersin.org/articles/10.3389/fendo.2022.1028114/full
Discussion
LADA vs. Classic T1D
Discussion of this study needs to start out with the question: Is it a LADA study, or is it a classic T1D study, and are they different?
The successful (early treatment) part of this study enrolled people between the ages of 17 and 58 (average age was 31 and standard deviation was 13 years), so about half of these people had LADA rather than classic type 1 diabetes. LADA stands for Latent Autoimmune Diabetes in Adults; you can think of it as classic T1D, but diagnosed in adults. A common cut off is 30 years old. People under that age are said to have classic T1D and after that age, LADA. LADA has a honeymoon, just as T1D does, but it is not the same. It is well known to be longer and stronger. This makes it easier for drugs that delay/extend the honeymoon to work better on LADA than on T1D. Therefore, we don't know if the good results seen here for many people with LADA are going to be as good in people with classic T1D.
Prospective vs. Retrospective Studies
I usually report on prospective studies, which are inherently more reliable than retrospective studies, and this study was retrospective. In this case, these researchers are already raising money for another study and that new study will be prospective, so it will provide a better signal as to the success of the treatment. In the meantime, there is nothing to do but wait, and hope they can raise the money quickly.
Similar Studies With Semaglutide
The obvious clinical trial to compare this to is the Semaglutide study which I blogged on here:
https://cureresearch4type1diabetes.blogspot.com/2023/09/strong-results-from-pilot-study-of.html
That study was in many ways very similar, both in study design and result. They were both retrospective studies based on clinical practice, and they both had many people off insulin for a year in the honeymoon phase.
Interestingly, Semaglutide has a similar mechanism of effect to Sitagliptin or Saxagliptin. They all end up impacting glucagon-like peptide-1 (GLP-1). However, Semaglutide is an injected drug while Sitagliptin and Saxagliptin (tested here) are pills.
Availability Now
The three drugs tested here are all commonly available. GABA is a dietary supplement, Omeprazole is sold both over the counter and by prescription. Only the second component: Sitagliptin or Saxagliptin is a prescription drug and both have been approved for use since the late 2000s. They each have a generally good safety profile. If you want to have an "off label" discussion with your doctor, the exact dosing information is in the clinical trial report (link above).
