Duodenal mucosal renewal plus semaglutide may lower HbA1c long term without insulin use
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Key takeaways:
- Twelve of 14 adults who underwent ReCET and received semaglutide maintained an HbA1c of less than 7.5% without using insulin.
- Improvements in time in range, fasting plasma glucose and BMI were also observed.
A novel duodenal mucosal renewal procedure followed by once-weekly semaglutide could allow adults with type 2 diabetes to maintain glycemic control without insulin therapy, according to a speaker.
Re-Cellularization via Electroporation Therapy (ReCET) is a procedure in which pulsed electric fields are used to induce natural death of dysfunctional duodenum lining without leading to thermal damage of deeper layers of the duodenum, according to an abstract from United European Gastroenterology (UEG) Week. In findings from a first-in-human study, ReCET was successfully completed in 14 adults with type 2 diabetes. One year after the procedure, the study group had a mean HbA1c of 6.6% with semaglutide 1 mg (Ozempic, Novo Nordisk), with 12 of 14 adults maintaining a normal HbA1c while off insulin.
“The impact of ReCET can be profound,” Celine B.E. Busch, MD, research associate in the department of gastroenterology and hepatology at Amsterdam University Medical Center in the Netherlands, told Healio. “The treatment is compliance-free, unlike drug therapy, which requires patients to take their medication day in and day out. Patient compliance is an important issue in the management of type 2 diabetes. In addition, the treatment is disease-modifying: It improves the patient’s sensitivity to their own insulin, thus tackling the root cause of the disease, as opposed to currently available drug therapies that are at best disease-controlling.”
HbA1c, BMI decrease at 1 year
Researchers enrolled 14 adults aged 28 to 75 years with type 2 diabetes using less than 1 U/kg of basal insulin daily and with an HbA1c of 8% or less at baseline. ReCET was performed in all participants and was followed by an isocaloric liquid diet for 2 weeks. Adults received up to 1 mg once-weekly semaglutide after the liquid diet was completed. The trial’s efficacy endpoint was the percentage of adults maintaining an HbA1c of 7.5% or less at 6 months without exogenous insulin.
ReCET was successfully completed in all participants, with no severe adverse events or severe hypoglycemic events related to the procedure. Thirteen of 14 participants tolerated the maximum dose of 1 mg semaglutide.
At 6 months, 12 of 14 adults had an HbA1c of 7.5% or less without the use of insulin. In addition, at 6 months, mean HbA1c dropped from 7.1% at baseline to 6.5% (P = .004), fasting plasma glucose declined from 8.8 mmol/L at baseline to 6.8 mmol/L (P = .004), time in range as measured by continuous glucose monitoring increased from 73% at baseline to 93% (P = .019) and BMI declined from 28.8 kg/m2 at baseline to 24.9 kg/m2 (P < .001). Participants also had reductions in insulin resistance, waist circumference and liver fat fraction from baseline to 6 months.
All 12 adults who achieved the efficacy endpoint at 6 months continued to maintain an HbA1c of 7.5% or less without insulin at 1 year. HbA1c was 6.6% at 1 year (P = .011 from baseline) and FPG decreased to 6.6 mmol/L (P = .003 from baseline). Time in range was 89% at 1 year (P = .011 from baseline). Mean BMI decreased to 22.6 kg/m2 at 1 year (P = .002 from baseline).
Glycemic control at 2 years
There were 11 adults who completed 2 years of follow-up, all of whom maintained an HbA1c of 7.5% or less without insulin. The mean HbA1c of 6.7% and mean FPG of 7.5 mmol/L at 2 years were not significantly less than baseline. However, participants continued to have a decrease in BMI, with a mean 23.6 kg/m2 at 2 years (P = .003).
Busch said researchers are currently conducting a sham-controlled, double-blind randomized trial where adults with type 2 diabetes are undergoing either ReCET or a sham procedure. All participants will receive semaglutide after the procedure.
“This study also includes mechanistic assessments to evaluate the underlying mechanism of ReCET,” Busch said.
Reference:
Busch CBE, et al. Gastrointest Endosc. 2024;doi:10.1016/j.gie.2024.04.2904.
For more information:
Celine B.E. Busch, MD, can be reached at c.b.busch@amsterdamumc.nl.
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Busch CBE, et al. OB049. Presented at: United European Gastroenterology Week; Oct. 12-15, 2024; Vienna.
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