A combination therapy using endoscopic duodenal ablation and semaglutide has demonstrated significant potential in eliminating insulin dependency in type 2 diabetes patients, according to new research presented at UEG Week 2024 in October.
Research presented at the United European Gastroenterology (UEG) Week 2024 in Vienna has revealed promising results from a first-in-human study combining a novel endoscopic procedure with semaglutide administration, potentially offering a new treatment pathway for type 2 diabetes patients dependent on insulin therapy.
Understanding the treatment approach
The study, which combined ReCET (Re-Cellularization via Electroporation Therapy) with semaglutide administration, demonstrated remarkable success in eliminating insulin dependency in 86% of participants over a 24-month period. The research addresses a significant clinical need, as type 2 diabetes affects approximately 422 million people globally, with many patients requiring daily insulin therapy despite its associated challenges such as weight gain and complex management requirements.
Mechanism of action
The ReCET procedure represents a significant advancement in endoscopic treatment approaches. It utilises electroporation to ablate the duodenal mucosa through a precisely controlled process that creates irreversible holes in cell membranes, leading to controlled cell death (apoptosis). Unlike traditional ablation techniques, ReCET avoids heat generation, thereby preventing damage to deeper wall layers of the duodenum. This innovative approach appears to enhance the body’s sensitivity to endogenous insulin, although researchers note that the exact mechanism requires further investigation.
Study design and outcomes
The research included 14 participants aged between 28 and 75 years, with body mass indices ranging from 24 to 40 kg/m². Following the ReCET procedure, which was performed under deep sedation, participants followed a two-week isocaloric liquid diet before beginning a graduated semaglutide treatment protocol, eventually reaching a target dose of 1mg weekly.
The results were particularly noteworthy, with 12 out of 14 participants maintaining glycaemic control without insulin therapy through the 24-month follow-up period. All successful cases maintained HbA1c levels below 7.5%, indicating effective blood glucose management.
Safety and tolerability
The study reported encouraging safety outcomes, with no serious adverse effects from the ReCET procedure. The semaglutide component was well-tolerated by 93% of participants, with only one individual unable to reach the maximum dose due to nausea. All participants successfully completed the ReCET procedure without significant complications.
Commenting on the research, lead author Dr Celine Busch, said: “These findings are very encouraging, suggesting that ReCET is a safe and feasible procedure that, when combined with semaglutide, can effectively eliminate the need for insulin therapy.”
Future research directions
The research team is currently conducting a larger randomised controlled trial, EMINENT-2, which will compare ReCET to a sham procedure while maintaining the same inclusion criteria and semaglutide administration protocol. This follow-up study will include mechanistic assessments to better understand the underlying processes of ReCET.
Dr Busch highlighted a key advantage of the treatment approach: “Unlike drug therapy, which requires daily medication adherence, ReCET is compliance-free, addressing the critical issue of ongoing patient adherence in the management of T2D. In addition, the treatment is disease-modifying: it improves the patient’s sensitivity to their own (endogenous) insulin, tackling the root cause of the disease, as opposed to currently available drug therapies, that are at best disease-controlling.”
Reference:
- Busch C.B.E, et al. (2024). Durable effects of duodenal ablation using electroporation combined with semaglutide to eliminate insulin therapy in patients with type-2 diabetes; the 24-month results. Paper presented at UEG Week 2024, Vienna, Austria, 14 October 2024.
