Introduction
Progressive hyperglycemia in type 2 diabetes (T2D) leads to the need for exogenous insulin therapy in many patients, which is associated with weight gain and hypoglycemia. Studies have shown that hydrothermal duodenal mucosal ablation improves glycemic control by improving insulin resistance. Re-Cellularization via Electroporation Therapy (ReCET) is a novel endoscopic procedure that uses electroporation to induce duodenal mucosal renewal. This technology uses pulsed electric fields to induce natural cell death through an apoptosis-like process without generating heat, thereby eliminating the risk of thermal damage to deeper layers of the duodenum. In this study, we aimed to eliminate insulin treatment in T2D patients with a single ReCET procedure combined with a GLP-1 receptor agonist (GLP-1RA, semaglutide). Here, we present our 24-month results.
Aims & Methods
Single-arm, single-center, first-in-human study in 14 patients with T2D (28-75 years, body mass index (BMI) 24-40 kg/m2, glycosylated hemoglobin (HbA1c) ≤8.0%, basal insulin dose <1U/kg/day, C-peptide ≥0.2 nmol/L). All patients underwent the ReCET procedure under deep sedation followed by a 2-week isocaloric liquid diet. Thereafter, semaglutide was titrated up to 1 mg/week. Primary feasibility endpoints were procedure time (catheter in–out), technical success, and % of patients tolerating GLP-1RA. Primary safety endpoints were (serious) adverse events ([S]AEs) and hypoglycemic events. Efficacy endpoint was the percentage of patients off exogenous insulin at 6 months while maintaining HbA1c ≤7.5%. Baseline and follow-up glycemic and metabolic data and treatment satisfaction scores were assessed.
Results
The technical success rate of the ReCET procedure was 100% (14/14 patients) with a median axial treatment length of 12cm. The median procedure time was 58 minutes (IQR 49–79). No device-related SAEs or severe hypoglycemic events were observed. The maximum dose of semaglutide was tolerated by 13 (93%) patients. At 6 and 12 months, 12 (86%) patients were still not using insulin, yet showed significant improvements in glycemic control (HbA1c) and metabolic parameters (Table 1). Eleven patients completed the 24-month follow-up; one patient withdrew consent after 18 months while in good glycemic control. All eleven remained off insulin with adequate glycemic control.
| | Baseline | 6 months | p-value | 12 months* | p-value | 18 months | p-value | 24 months | p-value |
| Number of patients | 14 | 14 | NA | 13 | NA | 12 | NA | 11 | NA |
| Haemoglobin A1c, % | 7.2 (7.0 – 7.4) | 6.6 (5.8 – 6.9) | 0.003 | 6.5 (6.1 – 7.0) | 0.011 | 6.7 (5.9 – 7.1) | 0.012 | 6.7 (6.0 – 7.4) | 0.126 |
| Fasting plasma glucose, mmol/L | 8.8 (7.6 – 10.6) | 6.8 (6.1 – 8.7) | 0.004 | 6.6 (5.8 – 7.2) | 0.003 | 7.6 (6.6 – 8.8) | 0.060 | 7.5 (6.8 – 8.1) | 0.286 |
| Homeostatic model assessment for insulin resistance | 5.84 (3.92 – 7.50) | 2.47 (1.50 – 3.25) | 0.013 | 1.78 (1.05 – 2.71) | 0.002 | 2.70 (1.44 – 4.81) | 0.041 | 3.16 (1.64 – 3.78) | 0.008 |
| Time in range, % | 72 (46 – 85) | 92 (79 – 96) | 0.019 | 89 (76 – 97) | 0.011 | 91 (81 – 93)** | 0.248 | 86 (78 – 98) | 0.062 |
| Weight, kg | 90.7 (82.3 – 104.2) | 77.6 (75.4 – 93.4) | <0.001 | 74.0 (67.2 – 98.6) | 0.002 | 74.5 (65.8 – 90.4) | 0.002 | 73.0 (64.4 – 89.5) | 0.003 |
| Body mass index, kg/m2 | 28.8 (25.1 – 31.2) | 24.9 (23.0 – 27.0) | <0.001 | 22.6 (22.1 – 27.1) | 0.002 | 22.9 (21.8 – 27.0) | 0.002 | 23.6 (22.2 – 26.8) | 0.003 |
| Waist circumference, cm | 107 (97 – 111) | 95 (85 – 99) | 0.002 | 91 (79 – 101) | 0.002 | 89 (81 – 98) | 0.003 | 93 (79 – 100) | 0.010 |
| Liver fat fraction, % | 9.2 (6.0 – 15.4) | 6.3 (4.3 – 10.5) | 0.030 | 4.2 (3.0 – 10.0) | 0.016 | NA | NA | 3.9 (1.8 – 9.8) | 0.006 |
Table 1. Glycaemic and metabolic secondary endpoints. Values are presented as median (interquartile range). Differences between the baseline, 6, 12, 18 and 24 months data were assessed using the Wilcoxon signed-rank paired test. *One patient was excluded due to steroid use. **One patient was excluded since GLP1-RA was discontinued once sensor was placed.
Conclusion
These results suggest that duodenal ReCET is feasible and safe. Combined with semaglutide, ReCET eliminated the need for insulin therapy in 86% of patients until 12 months post-treatment while improving glycaemia and metabolic health. Patients who were off exogenous insulin at 12 months had a durable glycaemic response and remained insulin-free at 24 months.
Disclosure
Unrestricted research grant from Endogenex.
