NEW YORK (Reuters Health) – The Revita procedure for duodenal mucosal resurfacing (DMR) improves blood glucose control, insulin sensitivity and pancreatic beta-cell function in patients with poorly controlled type 2 diabetes, according to data from the REVITA-2 trial.

The results, scheduled for presentation in San Francisco at the Endocrine Society annual meeting (ENDO 2020) were released March 30 during a virtual press conference.

Duodenal mucosal hyperplasia occurs early in diabetes and is a “principal driver of insulin resistance” and therefore a potential therapeutic target for metabolic diseases related to insulin-resistance, Dr. David Hopkins, director of the Institute of Diabetes, Endocrinology and Obesity, King’s Health Partners in London, told the briefing.

Revita DMR is a minimally invasive, outpatient, endoscopic procedure that causes hydrothermal ablation, partially removing a layer of the duodenal mucosa. It was developed by Fractyl Laboratories, which funded the study.

Previous research has demonstrated that DMR lowers hemoglobin A1c and reduces liver fat in patients with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD), compared to a sham endoscopic procedure, and appears to be safe. The REVITA-2 study was a randomized, sham-controlled clinical trial designed to elucidate the insulin-sensitizing mechanisms underlying the reported beneficial effects of DMR.

Dr. Hopkins reported on 70 patients (35 treated with Revita DMR and 35 with sham DMR) who underwent a mixed-meal tolerance test (MMTT) before and 12 weeks after treatment. MMTT determines insulin sensitivity and pancreatic beta-cell function.

Compared with patients who had sham DMR, those who received Revita DMR had significantly lower glucose levels, primarily driven by a decrease in fasting blood glucose (-41.0 mg/dL vs. -15.0 mg/dL, P=0.003), suggesting a primary effect on insulin resistance, Dr. Hopkins noted.

Revita DMR also led to improvements in insulin sensitivity and pancreatic beta-cell function, as evidenced by improvement in C-peptide levels and decreased postprandial glucagon elevation.

These results show “a broad range of metabolic benefits” of DMR and confirm that the duodenum is an “important therapeutic target” for type 2 diabetes, Dr. Hopkins said.

Patients who are failing on one or more oral anti-diabetes agents are likely best candidates for DMR, he noted. “We think it’s probably most appropriate relatively early in the course of diabetes where it has the greatest effect in terms of potentially changing the natural history of the condition that existing pharmacotherapy may not offer,” Dr. Hopkins said.

Dr. Harith Rajagopalan, Fractyl co-founder and CEO and study investigator, noted that data from REVITA-1 study suggest that the benefits of a single DMR procedure appear to last for least two years.

“As a consequence, we are anticipating that this could be a procedure with quite long-lasting benefits. We anticipate that in the future we may need to ask whether this procedure would need to be repeated and if so with what frequency and in which patients, but right now we appear to have evidence that this could be very durable,” he told the briefing.

Revita DMR has received regulatory approval in Europe but not yet in the United States.

“The concept is novel and interesting,” Dr. Joel Zonszein, director of the Clinical Diabetes Center at Montefiore Medical Center, in New York City, commented in an email to Reuters Health.

“Metabolic surgery is now part of the clinical armamentarium for type 2 diabetes, proven effective in short- and long-term outcomes. Bariatric surgery is evolving into interventions that are less focused on weight loss and more in interventions affecting the gut neurohormonal modulation,” said Dr. Zonszein, also a professor of clinical medicine at Albert Einstein College of Medicine.

“Revita therefore is an important player in this evolution of bariatric metabolic surgery. We need larger and longer studies in individuals with better glycemic control to see if the intervention has a role in the clinical management of type 2 diabetes,” Dr. Zonszein said.

“The duodenum plays an important role in neuroendocrine regulation (but) neuroendocrine regulation of the gastrointestinal tract is exceedingly complex,” he added.

Several authors are employed by Fractyl.

SOURCE: ENDO 2020, March 30, 2020.

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