Adults with type 2 diabetes have significantly improved hyperglycemia in the short term after single-procedure duodenal mucosal resurfacing, published data show.
Harith Rajagopalan, MD, PhD, co-founder, CEO and director of Fractyl Laboratories Inc., and colleagues evaluated 39 adults with type 2 diabetes who underwent duodenal mucosal resurfacing using novel balloon catheters on varying lengths of duodenum to determine the procedural safety and glycemic indices at 6 months.
Ablation of a long segment of duodenal mucosal was performed in 28 participants and 11 had a short segment ablated.
Immediately after the procedure and at later follow-up visits, there was no gastrointestinal bleeding, perforation, pancreatitis, severe hypoglycemia or evidence of malabsorption. Transient postprocedural abdominal pain due to air insufflation and/or endotracheal intubation was the most common study-related adverse event. Discomfort was not reported by any participants by 48 hours after the procedure.
At 6 months, HbA1c was reduced by 1.2% in all participants (P < .001). At 3 months, the long segment of duodenal mucosal resurfacing group had a 2.5% reduction in mean HbA1c compared with a mean reduction of 1.2% in the short segment duodenal mucosal resurfacing group (P < .05 between groups). At 6 months, the trend continued in both groups (long segment, 1.4%; short segment, 0.7%; P = .3 between groups).
“Our findings suggest that minimally invasive upper gastrointestinal intervention through [duodenal mucosal resurfacing] can improve glycemia in type 2 diabetes and represents an interesting potential adjuvant or alternative to pharmacological treatment,” the researchers wrote. “The [duodenal mucosal resurfacing] approach may overcome treatment adherence and compliance issues, a major shortcoming of all pharmacological approaches. [Duodenal mucosal resurfacing] also provides a window into the intriguing and specific role of the duodenum in regulating downstream metabolism. Further work is necessary to better understand the clinical utility of this procedure-based intervention in controlled trial conditions in larger numbers of patients.” – by Amber Cox
Disclosure: Rajagopalan reports being an employee and owning shares in Fractyl Laboratories Inc.
Bruce M. Wolfe
The rationale for this study is based on experimental and clinical research performed largely by the coauthors. The basis for this clinical trial is well-established. The authors state that the safety of the procedure is not an issue as no serious or life-threatening complications were observed. I am concerned, however, regarding the occurrence of three patients (7.7%) with duodenal strictures that required endoscopic balloon dilation. The authors indicate that unstated adjustments in procedure or technique are expected to eliminate this complication. I am concerned as a stricture requiring endoscopic dilation presumably involved most, if not all, of the full circumference of the duodenum at the site of the stricture. In order for a stricture to develop, inflammation presumably extended beyond the mucosa, suggesting that the separation of mucosa from muscularis and deeper layers of the duodenal wall did not occur. Thus, it is likely that full-thickness inflammation occurred. Should this progress to perforation, such a complication could be life threatening.
A number of questions remain to be answered by further research. These questions include whether the duodenal mucosa, as it regrows, will be normal or apparently abnormal as described by the authors. Whether the abnormal duodenal mucosa and its secondary neuroendocrine impact on glucose metabolism is a primary or secondary phenomenon is uncertain. It is, thus, difficult to predict at the present time whether the impact on clinical diabetes will be persistent beyond 6 months or not. Finally, the safety and efficacy will require clinical trials with greater numbers as well as controls for the observed weight loss (4.6% at 3 months, 3% at 6 months) as well as a possible sham effect: endoscopy and duodenal wall infiltration with saline.
The study is of definite interest given the hesitancy of patients to undergo major surgical procedures, such as gastric bypass.
Disclosure: Wolfe reports no relevant financial disclosures.