Source: Meiring S, et al. Abstract OP160. Presented at: UEG Week Virtual. Oct. 11-13, 2020.
Disclosures: This study was supported by an unrestricted grant from Fractyl Laboratories.
October 13, 2020
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More than half of patients with diabetes off insulin after duodenal resurfacing

Source: Meiring S, et al. Abstract OP160. Presented at: UEG Week Virtual. Oct. 11-13, 2020.
Disclosures: This study was supported by an unrestricted grant from Fractyl Laboratories.
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More than half of patients who underwent duodenal mucosal resurfacing remained insulin free and saw improved metabolic parameters at 6 months and 1 year, according to a study presented at UEG Week Virtual.

“The idea behind duodenal mucosal resurfacing or DMR is to cause rejuvenation of the duodenal mucosa and thus restore the altered hormonal signaling,” Suzanne Meiring, MD and PhD candidate at the Amsterdam University Medical Center in the Netherlands, said during her presentation. “This may be a game-changing approach in the treatment of the metabolic syndrome.”

Infographic on the percentage of patients who were inuslin-free after DMR-GLP-1RA treatment.
Patients who underwent duodenal mucosal resurfacing remained insulin free at 6 months and 1 year.

The INSPIRE study presented was a single-arm, single-center, open-label study in which DMR (Revita, Fractyl Laboratories) was performed in 16 patients. Inclusion criteria included having type 2 diabetes, receiving long-acting insulin, an HbA1c lower or equal to 64 mmol/mol and C-peptides greater than or equal to 0.5 nmol/L.

“That reflects adequate insulin production of the pancreas,” she said.

Meiring outlined the intervention strategies: DMR procedure performed and insulin stopped the same day. In the 2 weeks after the procedure, patients maintained a specific diet. At the 2-week mark, patients received GLP-1 receptor agonist Victoza (liraglutide, Novo Nordisk) and increased dosing in a stepwise manner. Additionally, “mild” lifestyle counseling was given during follow-up appointments every 4 to 12 weeks.

Follow-up appointments also included blood collection in which if the patient’s HbA1c was at 58 mmol/mol or lower, the GLP-1 remained in place. If it was higher than 58 mmol/mol, the GLP-1RA stopped and the patient restarted insulin. The primary endpoint was the percentage of patients off insulin at 6 months who maintained glycemic control.

Our results were better than expected,” Meiring said.

At 6 months, 75% of patients were insulin free. At 12 months, 58% were insulin free.

Despite eliminating insulin, Meiring showed that glycemic parameters improved. In responders, HbA1c at baseline was 7.4 and it decreased to 6.7 at 6 months (P = .009) and 12 months (P = .02). HOM-IR was 8.9 at baseline, decreasing to 2.6 at 6 months (P = .004) and 7.1 at 12 months (P = .008). Fasting glucose dropped from 10.5 at baseline to 7.6 at 6 months (P = .003) and 3.6 at 12 months (P = .015).

“A single endoscopic DMR, combined with GLP-1 receptor agonist and lifestyle counseling, can discontinue insulin therapy in a subset or patients with type 2 diabetes while improving parameters of glycemia and improving overall metabolic health,” Meiring said.

Additionally, the researchers reported improved metabolic parameters across the whole study population. Looking at BMI, Meiring showed that responders went from 29.8 kg/m2 at baseline to 27.2 kg/m2 at 6 months (P = .002) and 25.5 kg/m2 at 12 months (P = .008), whereas the overall population went from 29.2 mg/kg2 at baseline to 27.6 mg/kg2 at 6 months (P < .001) and 26.4 mg/kg2 at 12 months. Liver fat fell from 8.1% at baseline in responders to 4.6% at 6 months (P = .016) and 6% at 12 months. In the whole population, liver fat fell from 8.1% at baseline to 5.3% at 6 months and 5.6% at 12 months (P = .3).

“This effect slightly fades after 12 months, but the majority of patients were still off insulin,” she added. “We don’t know the effect of multiple DMRs, but it could extend or enlarge the effect.”

Meiring said mechanistic and larger studies are underway to determine the effect of the individual treatment components and understand how DMR contributes to the metabolic changes.