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A new endoscopic duodenal mucosal resurfacing treatment could lead to T2D patients becoming insulin-free.
Endoscopic duodenal mucosal resurfacing (DMR), combined with glucagon-like peptide (GLP)-1 receptor agonist, has been shown to improve glycemic control in patients with T2DM, possibly enabling them to discontinue insulin therapy.
The scientific journal, gut, has published the one-year results of a small, international, open-label, prospective, multicenter clinical trial, where 75% of study participants have been found to have adequate glycemic control (HbA1c < 58 mmol/mol, 7.5%) without needing insulin therapy six months after undergoing a single endoscopic DMR procedure.
The research was presented at UEG Week Virtual 2020, where Dr. Suzanne Meiring of Amsterdam University Medical Center in The Netherlands has explained that the novel endoscopic DMR procedure has rejuvenated the mucosa of the duodenum, restoring the altered hormonal signaling of the beta cells. Because of this, insulin sensitivity in the cells has increased, as indicated by the decline of the HOMA-IR values from an average of 8.9 at baseline to 2.6 after six months, while fasting blood glucose has dramatically improved from 169.0 mg/dL (10.5 mmol/L) to 136.8 mg/dL (7.6 mmol/L) during the same time frame.
The DMR is an endoscopic procedure, which involves a catheter-based circumferential mucosal lifting followed by hydrothermal ablation of the duodenal mucosa, which is the part of the intestine just beyond the stomach. It can be performed within 45 minutes, making it minimally invasive compared to bariatric surgery, and can be carried out by a specialist with sufficient training. Dr. Meiring said it is not clear yet why the procedure works. Still, they believe that the effects result from a combination of changes in hormonal signaling that occur when the duodenal mucosa is ablated and rejuvenated, including the gut hormone GLP-1, bile acid compositions, and the microbiota.
The study enrolled 46 adult patients, aged 28 to 75 years, with a clinical diagnosis of T2DM and a body mass index (BMI) of 24-40 kg/m2 and an HbA1c of 59-86 mmol/mol (or 7.5%-10.0%). They were on a stable antidiabetic treatment comprising at least one GLP-1 receptor agonist (e.g., Victoza, Trulicity, Ozempic) for at least three months. The study participants took long-acting insulin before the DMR procedure, at an average dose of 31 units of insulin per day, and had adequate insulin production as indicated by the C-peptide level of at least 0.5 nmol/L.
On the day of the procedure, study participants were asked to stop taking their insulin. The GLP-1 receptor agonist was continued two weeks after and increased subsequently in a stepwise fashion to a daily dose of liraglutide 1.8 mg given subcutaneously. Aside from the medication, the participants also received counseling on lifestyle factors such as a healthy diet and physical activity. If the patient’s HbA1c rose to above 58 mmol/mol (7.5%), the GLP-1 receptor agonist was stopped, and insulin restarted.
In addition to HbA1c levels decreasing to 6.7% after 12 months, the results also showed a positive effect on patients’ overall metabolic health, as evidenced by a liver fat reduction among responders from an average of 8.1% before the procedure to 4.6% after six months. Simultaneously, patients’ average BMI also fell from 29.8 kg/m2 at baseline to 27.2 kg/m2, a clinically relevant weight loss.
Regarding the adverse effects (A.E.) of DMR, 24 patients (52%) had at least one A.E. related to DMR, of which 81% were deemed mild. However, only one patient experienced severe A.E. (mild fever and general malaise), and no unanticipated A.E.s were reported.
One year from the DMR procedure, the positive effects had slightly declined, but most patients were still off of insulin, 56%, compared to 75% six months prior. Hence, it can be hypothesized that multiple DMRs can help extend the effects of an insulin-free period of patients with T2DM, although this hypothesis remains to be tested.
Even though the mechanism remains unclear, the DMR procedure has shown promise in the treatment of T2DM among adult patients. Indeed, it may be a “game-changing approach in the treatment of metabolic syndrome,” per Dr. Meiring; it is now being tested in the United States through a large international trial called “Revita T2Di Pivotal Study.”
Practice Pearls:
- Duodenal mucosal resurfacing (DMR) has been shown to improve glycemic control in 75% of study participants, possibly enabling insulin therapy discontinuation in patients with T2DM.
- DMR is an endoscopic procedure, which involves a catheter-based circumferential mucosal lifting followed by hydrothermal ablation of the duodenal mucosa.
- DMR also reduced the BMI of patients and the % of liver fat in the body.
References for “Insulin-Free Treatment For T2DM Patients”:
Arjay Mendoza, PharmD Candidate, University of Colorado Denver Skaggs School of Pharmacy and Pharmaceutical Sciences