Among patients with suboptimally controlled type 2 diabetes who use oral glucose-lowering medication, endoscopic duodenal mucosal resection (DMR) can be implemented safely and effectively, results from a multicenter, international, phase 2 study demonstrated.
“DMR elicited a substantial improvement in parameters of glycemia as well as a decrease in liver transaminase levels at 24 weeks, which was sustained at 12 months post procedure,” researchers led by Annieke C.G. van Baar, MD, wrote in a study published online in. “These findings were also associated with an improvement in patients’ diabetes treatment satisfaction.”
For the study, Dr. van Baar, of the department of gastroenterology and hepatology at Amsterdam University Medical Center, and colleagues at seven clinical sites enrolled 46 patients with type 2 diabetes who were on stable glucose-lowering medication to undergo DMR. The procedure “involves circumferential hydrothermal ablation of the duodenal mucosa resulting in subsequent regeneration of the mucosa,” they wrote. “Before ablation, the mucosa is lifted with saline to protect the outer layers of the duodenum.” DMR was performed under either general anesthesia or deep sedation with propofol by a single endoscopist at each site with extensive experience in therapeutic upper GI endoscopy and guidewire management.
The mean age of the study participants was 55 years and 63% were male. Of the 46 patients, 37 (80%) underwent complete DMR and results were reported for 36 of them. A total of 24 patients had at least one adverse event related to DMR (52%), mostly GI symptoms such as diarrhea, abdominal pain, nausea, and oropharyngeal pain. Of these, 81% were mild. One serious adverse event was considered to be related to the procedure. “This concerned a patient with general malaise, mild fever, and increased C-reactive protein level on the first day after DMR,” the researchers wrote. “The mild fever resolved within 24 hours and [C-reactive protein] level normalized within 3 days.” No unanticipated adverse events were reported.
During follow-up measures taken 24 weeks after their DMR, hemoglobin A1c fell by a mean of 10 mmol/mol (P less than .001), fasting plasma glucose by 1.7 mmol/L (P less than .001), and the Homeostatic Model Assessment of Insulin Resistance improved significantly (P less than .001). In addition, the procedure conferred a moderate reduction in weight (a mean loss of 2.5 kg) and a decrease in hepatic transaminase levels. The effects were sustained at 12 months.
“While the majority of patients showed a durable glycemic response over 12 months, a minority exhibited less benefit from DMR and required additional glucose-lowering medication at 24 weeks,” the researchers wrote. “Of note, approximately two-thirds of the patients who required addition of antidiabetic medication in the latter phase of study had undergone insulin secretagogue medication withdrawal at screening. For future study, it may not be necessary to discontinue these medications before DMR, and this will allow an even more precise measure of DMR effect.”
Dr. van Baar and colleagues acknowledged certain limitations of the phase 2 study, including its open-label, uncontrolled design. “The results of this multicenter study need to be confirmed in a proper controlled study. Nevertheless, this study forms the requisite solid foundation for further research, and controlled studies are currently underway.”
The study was funded by Fractyl Laboratories. Dr. van Baar reported having no financial disclosures. Four of the study authors reported having financial relationships with numerous pharmaceutical and device companies.
SOURCE: van Baar ACG et al. Gut. 2019 Jul 22. .