Endoscopic Duodenal Resurfacing May Eliminate Need for Insulin in Type 2 Diabetes

By Megan Brooks

October 13, 2020

NEW YORK (Reuters Health) - A single endoscopic duodenal mucosal resurfacing (DMR), coupled with a GLP-1 receptor agonist and lifestyle coaching, can eliminate the need for insulin in most type 2 diabetes patients and improve glucose regulation and overall metabolic health, according to results of a pilot study.

"This may be a game-changing approach in the treatment of metabolic syndrome," Dr. Suzanne Meiring of Amsterdam University Medical Centre, in the Netherlands, said during a presentation of the results at the virtual United European Gastroenterology (UEG) Week 2020.

Duodenal mucosal hyperplasia occurs early in diabetes and contributes to insulin resistance. Revita DMR, developed by Fractyl Laboratories, which funded the study, is a minimally invasive, outpatient, endoscopic procedure that causes hydrothermal ablation, partially removing a layer of the duodenal mucosa.

DMR has been shown to improve insulin sensitivity and improve glycemic control in patients with type 2 diabetes. The current study tested the feasibility of eliminating exogenous insulin therapy by combining DMR with a GLP-1RA (liraglutide) and lifestyle counseling.

Participants included 16 patients (mean age, 61; 10 men) with type 2 diabetes on long-acting insulin only. After a single DMR, all patients discontinued insulin, started liraglutide (1.8 mg/day stepwise) and received lifestyle counseling from a dietician.

At six months, 12 of the 16 patients (75%) were off insulin therapy, with hemoglobin (Hb)A1C of 7.5% or lower and this was associated with significant improvement in all glycemic and metabolic parameters, Dr. Meiring reported.

In the 12 responders, from baseline to six months, median HbA1C improved from 7.4% to 6.7%; homeostatic model assessment of insulin resistance (HOMA-IR) improved from 8.9 to 2.5; and fasting plasma glucose (FPG) improved from 10.5 to 7.6 mmol/l. Liver fat was also significantly improved from 8.1% to 4.6% and body mass index (BMI) was reduced from 29.8 to 27.2 kg/m2.

At 12 months, 56% of the patients (9/16) were still off insulin therapy with a median HbA1C of 6.7% and glycemic and metabolic parameters maintained significantly improved.

"The effect of DMR slightly fades after 12 months, but the majority of patients is still off insulin. We haven't assessed the effect of multiple DMR treatments or renewed treatment yet, but that could possibly extend or enlarge the effect," Dr. Meiring said.

She noted that this is an uncontrolled pilot study with a limited sample size, and the contribution of each of the individual treatment components is unknown. "The data must be confirmed by new multicenter randomized control trials. Based on these results, a large international randomized control trial has been started," she said.

Commenting on the results in email to Reuters Health, Dr. Jan Martinek, member of the UEG Public Affairs Committee, said this study brings "another important piece of evidence that DMR may be an interesting and effective mini-invasive therapeutic approach for patients suffering from type 2 diabetes. "

"The results are very promising," said Dr. Martinek, of the Institute of Clinical and Experimental Medicine (IKEM) in Prague. "Importantly, there were positive effects of a single DMR regarding other outcomes. For example, BMI decreased and the content of fat in the liver decreased. This seems very encouraging in the view of our current global 'pandemic' of fatty liver, especially in patients with type 2 diabetes. Maybe, we are witnessing a breakthrough event, but, as always in medicine, we should keep our feet on the ground and await further development."

As the study only included 16 patients, the results "should be considered as preliminary and another proof-of-concept," he noted.

Dr. Martinek said several questions need to be answered in the near future. "For example, what is the effect of multiple DMR sessions? I would also like to know how duodenal histology changed. Moreover, more endocrine assessment would be interesting to try to elucidate the mechanism behind promising clinical results. Lastly, adverse events have not been shown; probably there were no major adverse events, but as resurfacing is a new principle, we should look at both periprocedural and long-term safety," he told Reuters Health.

Fractyl Laboratories funded the study. One investigator reports financial ties to the company.

SOURCE: https://ueg.eu/week United European Gastroenterology (UEG) Week 2020, presented October 12, 2020.