Can a New Procedure Help People with Type 2 Diabetes on Insulin?
A new procedure called DMR (duodenal mucosal resurfacing) is being studied in clinical trials to see if it can help people with type 2 diabetes improve their A1C without the need for insulin.
Fractyl Health, a biotech company focused on addressing the causes of type 2 diabetes, is testing a new therapy called Revita DMR. This therapy has been approved in Europe but has not received FDA approval in the United States.
In Europe, it is indicated for people with type 2 diabetes who are still producing insulin but have not been able to achieve their desired A1C levels with oral and/or injectable glucose lowering medications and/or long-acting insulin therapy. It has also been indicated to reduce liver fat in people with type 2 diabetes and non-alcoholic fatty liver disease and to improve insulin sensitivity in insulin-resistant women with polycystic ovary syndrome.
DMR is a one-time, minimally invasive, outpatient procedure that takes about an hour. The therapy is in clinical trials to evaluate its effectiveness, and in prior clinical trials of over 300 people, there have been no long-term adverse events reported for up to two years post-procedure.
Researchers have identified that a section of our intestines called the duodenum may contribute to insulin resistance – in particular, diets high in fat and sugar cause the lining of our duodenum to thicken over time and stop functioning normally. The DMR procedure first delivers fluids into the gut that help the duodenum lining expand, and then, with thermal shock (targeted heat treatment), excess layers of the lining that are causing it to malfunction are removed. The duodenum can then create a new, healthy lining within a few days.
Potentially, this procedure could help people with type 2 diabetes improve their glucose management without the need for insulin injections by increasing their insulin sensitivity. Earlier this year, the FDA granted a Breakthrough Device Designation for Revita DMR. This designation means that the FDA believes a device exhibits promise, and it plans to accelerate the development, assessment, and review, hopefully speeding up the timeline for which it could become available.
Clinical Trials Identifier: NCT04419779
Trial Name: Revitalize-1 (formerly REVITA-T2Di)
Diabetes Type: Type 2 diabetes on insulin
Trial Sponsor: Fractyl Laboratories, Inc.
What is the trial testing?
This study is looking to enroll 428 participants into this randomized trial. Participants will be split into two groups: those who receive DMR treatment and those who receive a “sham treatment.” The two procedures are identical, except in the sham treatment, the procedure will not include the part that removes the excess layers in the duodenum lining.
After the procedure, all participants will be monitored for 48 weeks. Researchers will follow up with six in-person visits (either in the study center or at home) and five phone call visits. During this time, researchers may wean participants from insulin treatment and adjust their other medications as needed. After 48 weeks, all participants who initially received the sham treatment will be offered the DMR procedure. If they opt for this, they will be followed for 24 additional weeks.
The researchers will primarily be measuring the percentage of participants who achieve an A1C less than or equal to 7.0% without the need for insulin at 24 weeks after the treatment (this is the primary endpoint of the study).
Why is this trial new and important?
This new procedure has the potential to have positive impacts on people with type 2 diabetes. The procedure could help improve insulin sensitivity and reduce insulin resistance, which is the main cause of type 2 diabetes. In addition, it could lead to people having to take less medications (and less injected medications) overall for their diabetes management – reducing costs and potential side effects (such as hypoglycemia which can be associated with insulin).
A few of the clinical trials conducted to date on the DMR procedure have shown encouraging results. One small early trial with 46 adults who were on at least one oral glucose-lowering drug (and not on insulin) showed that DMR led to an A1C reduction of approximately 0.9 percentage points at 24 weeks (from an average of 8.6% to an average of 7.7%). Though this is not a direct comparison to this trial (since the participants were not on insulin), it does help show that the procedure could be safe and effective for some populations – in the 46 participants there was only one serious adverse procedure-related event reported, and this event was resolved completely within three days.
In addition, in another very small study of 16 adults with type 2 diabetes on basal insulin, it was shown that the procedure, coupled with lifestyle counseling and GLP-1 receptor agonist, led over half of the participants being taken off insulin and achieving an A1C less than or equal to 7.5% with no serious adverse events.
It’s important to note that these early clinical trials included very small number of participants and are not the only clinical trials that have been conducted for the DMR procedure. Over 300 procedures have been carried out in all clinical trials and in Europe to date. So far, DMR has been shown to be safe and effective with no long-term adverse events. Though there were positive outcomes and few adverse events reported, until more trials are conducted (like this one), it cannot be known for sure the overall safety and effectiveness of this procedure.
The DMR procedure is being investigated to see if it can help people lower their A1C and potentially reduce or even remove the need for insulin injections. Side effects of the procedure include but are not limited to stomach pain, bleeding, diarrhea, delayed stomach emptying, and nausea.
Trial Length: 48 to 72 weeks (depending on whether the participant is in the sham arm of the trial and chooses to continue with the study and receive the DMR treatment)
Trial Location: Several locations in the US and Europe. You can find a full list of locations here.
Are you interested?
You may be eligible for this study if you:
Are 21 to 70 years old.
Have type 2 diabetes.
Are currently on metformin and require at least 20 to 60 units of basal insulin (not MDI). If you are using other diabetes drugs in addition to insulin and are willing to replace those medications with metformin, you may also qualify for the study after 3 months of a washout period where you are weaned off your additional drugs and start on Metformin (if not already on it).
Are not pregnant or breastfeeding.
Have an A1C between 7.5-9.5%.
Have a BMI between 28 and 40.
Have not had more than one severe hypoglycemic episode or unawareness within the past six months.
This trial has a screening period of around three months. During the screening period, researchers will meet with you three to four times to determine if you are a suitable candidate for the trial and adjust your medications as needed. You can see a full list of eligibility and exclusion criteria here, and you can fill out this form to see if you qualify for the study.