Minimally Invasive DMR Scores a Win in T2D

An investigative minimally invasive endoscopic mucosal ablative procedure improved metabolic profiles of people with poorly controlled type 2 diabetes, researchers reported.

In the REVITA-2 study, participants who underwent duodenal mucosal resurfacing (DMR) saw significant lower median glucose levels, after a mixed meal tolerance test, after 12 weeks (area under the curve for glucose -36.38 mg/dL vs -4.94 mg/dL for a sham procedure, P=0.009), reported David Hopkins, MBChB, of King's Health Partners in London, at the virtual ENDO 2020 meeting sponsored by the Endocrine Society.

In those who underwent DMR, reduction in glucose levels was mainly driven by an improvement in fasting plasma glucose (FPG), but not postprandial glucose excursion:

• FPG: -41.0 mg/dL for DMR vs -15.0 mg/dL for sham (P=0.003)
• Postprandial glucose: -4.63 mg/dL vs 5.34 mg/dL (P=0.209)

People who had very high FPG prior to undergoing the procedure -- baseline levels of 180 mg/dL or higher -- saw the most benefit post-procedure, with the more marked reduction in fasting glucose:

• FPG ≥180: -63.03 mg/dL for DMR vs -20.31 mg/dL for sham (P=0.007)
• FPG <180: -26.81 mg/dL vs 13.81 mg/dL (P=0.271)

This subset of patients who started with the fasting glucose levels of 180 mg/dL or higher also reaped other metabolic benefits, in the form of significant increases in postprandial C-peptide excursion (0.41 ng/mL for DMR vs 0.02 ng/mL for sham, P=0.012) and significant drops in postprandial glucagon excursion (-8.03 pg/mL vs 2.13 pg/mL, P=0.027).

"These findings demonstrate that the Revita DMR procedure has major changes on the glucose metabolism in diabetes, and indicates an apparent effect on some of the underlying defects that drive type 2 diabetes," Hopkins explained during a virtual press conference.

The multicenter prospective study included 70 patients who were blindly randomized to the DMR procedure or a sham procedure. A little over half of patients in each group had baseline fasting plasma glucose levels of 180 mg/dL or higher. All patients were overweight, with a BMI between 24 to 40, and had HbA1c levels between 7.5% to 10%. Each participant was also on a stable oral anti-diabetic regimen of at least one agent.

The outpatient procedure works using hydrothermal ablation to remove the excessive layoff of the duodenal mucosa, which usually develops in response to a high-fat, high-sugar diet. The physician uses a console and a novel single-use balloon catheter to access the duodenum, and after the heat ablation, the body regenerates a healthy, new duodenal lining.

Immediately after the procedure, patients are advised to follow a liquid-only diet, slowly transitioning to soft foods, and returning to regular foods within 2 weeks. Hopkins stressed that patients are encouraged to maintain a long-term healthy lifestyle post-procedure.

Building on previously reported topline findings, the DMR procedure also significantly reduced HbA1c after 24 weeks versus sham (median change of -0.6% vs -0.3%, P=0.033). There was also a significant reduction in liver fat content after the procedure (median absolute change -5.4 vs -2.4 liver MRI-PDFF, P=0.039).

"Taken together with the other findings ... these data show a broad range of metabolic benefits of DMR and potential to alter the natural history of type 2 diabetes in a way that existing pharmacotherapy may not offer," Hopkins added.

He stated that the procedure works effectively in patients who still have some degree of preserved insulin secretion, and is likely "most appropriate" for those patients who are relatively early in their diabetes trajectory, where this procedure would yield the "greatest benefit" in changing the natural progression of the disease.

But the procedure would still likely benefit a very broad range of patients who may be deemed candidates for this treatment, he added.

"Once the [COVID-19] pandemic ends, the first clinical commercial service will launch fully in London," Hopkins told MedPage Today, when asked when this treatment will be readily available for patients. The procedure has a CE mark in Europe, and became available for commercial use in the U.K. in January. Fractyl Laboratories, Revita DMR's developer, announced plans for a U.S. pivotal clinical trial (estimated study start by end of 2020).

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