Duodenal Mucosal Resurfacing Lowers HbA1c in Early Study

Marlene Busko

August 13, 2019

A small, international, open-label, single-arm study hints that duodenal mucosal resurfacing added to pharmacotherapy could benefit patients with uncontrolled type 2 diabetes.

In 36 patients who had uncontrolled diabetes despite medication, the average initial HbA1c of 8.6% dropped by 0.9% at 6 months after they underwent ablation, and the decrease in HbA1c was sustained at 1 year.

This clinically meaningful improvement in glycemic control was seen without invasive bariatric surgery and the degree of improvement was similar to adding another pharmaceutical agent, Annieke C.G. van Baar, MD, from Amsterdam University Medical Center, the Netherlands, and colleagues report in their study published online July 22 in Gut.

The procedure is "feasible, safe, and effective," they summarize.

The study suggests that duodenal mucosal resurfacing "may have a role as an adjuvant or alternative approach to pharmacological treatment" in patients with type 2 diabetes.

And it "adds to the growing body of evidence that the GI tract, and particularly the duodenum, is an important target for interventions to treat [type 2 diabetes]."

van Baar and colleagues admit, however, that limitations include the study was open-label and lacked a control (sham procedure) arm.

The researchers are currently conducting a study with a control arm as well as a trial to see if there is any synergistic effect when duodenal mucosal resurfacing is added to treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist plus lifestyle intervention.

Duodenum Seems to Play a Role in Glucose Regulation

In patients who are moderately obese and have type 2 diabetes, bariatric surgery — whereby nutrients bypass the duodenum — improves glycemia, the group writes.

And as previously reported in 2016, a first-in-human study in 39 patients in Chile showed that patients had improved HbA1c levels 6 months after duodenal mucosal resurfacing with the Revita system (Fractyl).

To extend this work, the group screened 104 patients at seven sites in the Netherlands, Belgium (2 sites), UK (2 sites), Italy, and Chile.

Eligible patients had type 2 diabetes, were aged 28-75 years, had a body mass index (BMI) of 24-40 kg/m,2 and an HbA1c of 7.5%-10% and were taking at least one oral glucose-lowering drug but not receiving an injectable antidiabetic medication such as insulin or a GLP-1 agonist.

Of the screened patients, 55 were ineligible and three were excluded because of anatomy, technical problems, or consent withdrawal, leaving 46 patients in the intent-to-treat group.

Patients were a mean age of 55 years and 37% were women. They had had diabetes for a mean of 6 years and had a mean BMI of 31.6 kg/m2.

At screening, participants were receiving metformin (94%), sulfonylurea (37%), meglitinide (4%), a dipeptidyl peptidase-4 (DPP-4) inhibitor (22%), a sodium-glucose cotransporter-2 (SGLT2) inhibitor (11%), or pioglitazone (2%).  

Of the 46 patients, 37 patients (80%) underwent endoscopic duodenal mucosa resurfacing, which involves circumferential hydrothermal ablation of the duodenum, with subsequent mucosa regeneration.

Patients were discharged on the same or following day and instructed to follow a 2-week diet that transitioned from clear liquids to solids.

Sulfonylurea and meglitinide were discontinued at time of screening to lower the risk of hypoglycemia. One patient violated the study protocol by taking insulin and was excluded from the analysis.

There were 54 procedure-related adverse events reported in 24 patients (52%) in the 1-year follow-up: 40 cases of GI symptoms (diarrhea, abdominal pain, nausea, and oropharyngeal pain); 11 cases of malaise, fatigue, musculoskeletal pain, or rash; and three cases of hypoglycemia or hyperglycemia.

Most adverse events (81%) were mild and none were severe. There was one procedure-related serious adverse event and no unanticipated ones.

HbA1c levels decreased 4 weeks after the procedure and then fell further and stabilized at a lower level at 24 weeks and 1 year.

Patients had a mean weight loss of 2.3 kg, which "cannot explain the substantial HbA1c decrease" over the 12 months, according to the authors.

There was a clinically significant improvement in insulin resistance out to 1 year, and patient-reported treatment satisfaction also improved.

The study was funded by Fractyl Laboratories. van Baar has reported no relevant financial relationships. Disclosures of the other authors are listed with the article.  

Gut. Published online July 22, 2019. Abstract

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