Electroporation a promising way to end insulin dependency in T2D

A novel endoscopic electroporation procedure, when combined with semaglutide, can eliminate the need for insulin injections for individuals with type 2 diabetes (T2D), as shown in the results of the first-in-human EMINENT study.

Called re-cellularization via electroporation therapy (ReCET), the procedure uses electroporation, a technique where electric fields are applied to remove the superficial layer of the mucosa in the small intestine. The rejuvenation of the duodenal lining, when combined with the use of a GLP-1 receptor agonist, is expected to reduce insulin resistance in T2D, thus addressing the root cause of disease, according to researchers from the Amsterdam University Medical Center, Amsterdam, Netherlands.

ReCET stands out among other ablation methods in that the novel procedure does away with using extreme heat or cold to ablate the intestinal tissue, they noted.

“[Instead], ReCET uses a pulsed electric field, which can be precisely controlled and has a limited depth of penetration,” lead study researcher Dr Celine Busch pointed out. “It doesn’t directly physically damage the mucosa. Instead, it disrupts the cellular membrane of the mucosa and superficial submucosa. These cells subsequently die of natural cell death within 24 hours of the procedure. There is no increase in temperature during the procedure, which significantly reduces the chance of complications.”

Freedom from insulin

In the single-arm pilot study EMINENT, Busch and colleagues tested ReCET in 14 adults with T2D who were using long-acting basal insulin to control their blood glucose levels. The participants underwent the hour-long ReCET procedure and were initiated on semaglutide 2 weeks later.

ReCET was successful in 100 percent of the participants, with none of them experiencing serious adverse events associated with endoscopy. Furthermore, 93 percent of the participants were able to tolerate the maximum dose of semaglutide. [Digestive Disease Week 2023, abstract 1272]

As for efficacy, 86 percent of the participants had been able to keep their blood sugar levels in check while remaining insulin-free at the 12-month follow-up. Fasting plasma glucose levels dropped from 158 mg/dl at baseline to 119 mg/dl at 12 months, while HbA1c decreased from 7.2 percent to 6.6 percent (p=0.010).

ReCET also led to a greater than 50-percent reduction in liver fat percentage, Busch said. Meanwhile, cholesterol, low-density lipoprotein (LDL), and triglyceride levels showed a trend toward improvement, but the changes were not statistically significant.

One and done

“One of the biggest advantages is that [ReCET] is compliance-free,” Busch said. “Patients with T2D are generally on six to eight different drugs, and many are not taking these drugs correctly.”

Dr Jacques Bergman, the principal study investigator, added that just a single outpatient procedure combined with semaglutide proved to be capable of either reducing or eliminating the need for insulin.

“This is one of the first times that endoscopy has been used to improve glycaemic control in patients with T2D,” said Bergman.

Unanswered questions

One of the study’s limitations is the absence of a control group. Busch noted that the single-arm nature of the study makes it difficult to discern the individual effects of ReCET and semaglutide on glycaemic control. Nevertheless, the researcher believes that these approaches could be synergistically at play.

“In most studies in which patients on long-acting insulin receive a GLP-1 receptor agonist, less than 20 percent can stop insulin completely,” according to Busch.

“It’s difficult to explain our results based on just the activity of semaglutide. We know that GLP-1 receptor agonists boost the release of endogenous insulin. This acts synergistically with the insulin-sensitizing effect of ReCET, as reflected in an 86-percent success rate at 6, 9, and 12 months follow-up,” she continued.

Busch and Bergman shared that a randomized controlled trial is in the works to validate the present findings.