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Duodenal Mucosal Resurfacing Combined With GLP-1RA to Discontinue Insulin in Type 2 Diabetes
TAKE-HOME MESSAGE
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In this single-arm, prospective, open-label study, the authors examined the feasibility of combining lifestyle modifications, duodenal mucosal resurfacing (DMR), and a GLP-1RA in eliminating the need for insulin in patients with type 2 diabetes (T2D). In total, 16 patients with T2D underwent DMR combined with a GLP-1RA. At 6 months, 69% were off insulin and had an HbA1c level <7.5%. At 12 and 18 months, 56% and 53% remained off insulin, respectively (compared with 9% of patients who replaced their insulin therapy with only a GLP-RA in prior studies). The treatment combination had a favorable safety profile, with patients experiencing minimal gastrointestinal symptoms, requiring minimal to no analgesic treatment, and no device-related or treatment-related serious adverse events.
- Combining DMR with GLP-1RA and lifestyle modifications may be a safe, effective treatment for eliminating the need for insulin therapy in patients with T2D. Randomized sham-controlled studies are currently underway to confirm these findings.
abstract
This abstract is available on the publisher's site.
Access this abstract nowBACKGROUND AND AIMS
Duodenal mucosal resurfacing (DMR) is an endoscopic intervention in which the duodenal mucosa is ablated by hydrothermal energy. DMR improves glycemic control in patients with type 2 diabetes (T2D), most likely by altered duodenal signaling leading to insulin sensitization. We studied whether we could discontinue insulin use in T2D patients by combining DMR with glucagon-like peptide-1 receptor agonism (GLP-1RA) and lifestyle counseling.
METHODS
Single-arm, single-center feasibility study in 16 insulin treated T2D patients (HbA1c ≤8.0%; basal insulin <1U/kg/day, c-peptide ≥0.5 nmol/L). Patients underwent a single DMR followed by a 2-week postprocedural diet, after which GLP-1RA (liraglutide) was introduced. Lifestyle counseling was provided per ADA guidelines. The primary endpoint was percentage of patients without insulin with an HbA1c ≤7.5% (responders) at 6 months. Secondary endpoints were changes in multiple glycemic and metabolic parameters and percentage of responders at 12 and 18 months, respectively.
RESULTS
All 16 patients underwent successful DMR without procedure-related serious adverse events. At 6 months, 69% of patients were off insulin therapy with an HbA1c ≤7.5%. At 12 and 18 months 56% and 53% remained off insulin, respectively. All patients significantly improved in glycemic and metabolic parameters: Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), BMI, weight, and liver fat fraction.
CONCLUSIONS
n this feasibility study, the combination of a single DMR and GLP-1RA, supported by lifestyle counselling eliminated the need for insulin therapy in the majority of patients with T2D through 18 months postprocedure, with adequate beta-cell capacity, while improving glucose regulation and metabolic health in all patients. A randomized-sham controlled trial is currently initiated based on these results.
Additional Info
Disclosure statements are available on the authors' profiles:
Duodenal Mucosal Resurfacing Combined With GLP-1RA to Discontinue Insulin in Type 2 Diabetes: A Feasibility Study
Gastrointest. Endosc. 2020 Dec 23;[EPub Ahead of Print], ACG van Baar, S Meiring, P Smeele, T Vriend, F Holleman, M Barlag, N Mostafavi, JGP Tijssen, MR Soeters, M Nieuwdorp, JJGHM BergmanFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Gastroenterology
Obesity and its related comorbidities have become a global epidemic, leading to considerable burden to the healthcare system. The World Health Organization estimates that 650 million people worldwide are obese, with an estimated 93 million people in the United States. Intensive lifestyle interventions and pharmacotherapy are low-risk but also have limited efficacy. Bariatric surgery is very effective; however, only 1% to 2% of eligible patients end up undergoing these procedures given the risk profile, limited access, high cost, and patient preference.
In recent years, endoscopic bariatric and metabolic therapies (EBMTs) have been developed for patients with obesity who are not candidates for, or do not desire, bariatric surgery. Whereas gastric EBMTs are designed to treat obesity, small-bowel EBMTs are directed at treating metabolic diseases, with variable efficacy in weight loss. Recent data suggest that combination therapy using gastric interventions and pharmacotherapy may act synergistically, using the physiology and mechanism of action of individual therapies to augment weight loss.
To date, there are no existing data on small-bowel EBMTs in combination with pharmacotherapy. These authors examine duodenal mucosal resurfacing (DMR), a small bowel EBMT that applies hydrothermal energy to ablate the duodenum, in combination with liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA). Among its many mechanisms, this medication amplifies glucose-stimulated insulin secretion. As the duodenum is important for regulating metabolic homeostasis, alteration to the mucosa is hypothesized to affect glycemic metabolism by an insulin sensitization effect. As such, these authors reasoned that the insulin-sensitizing effect of DMR might be strengthened by coadministration this GLP-1RA. This single-center, prospective, open-label feasibility study found that this combination successfully eliminated the need for insulin therapy in a subset of patients with type 2 diabetes, and it adds to the growing body of literature supporting the use of endoscopic interventions in combination with pharmacotherapy to treat obesity and metabolic diseases. These exciting data should help guide future randomized controlled trials to confirm and further understand these findings.