Key takeaways:
- Adults undergoing duodenal mucosal resurfacing maintained 81% of their weight loss with tirzepatide at 1 year.
- Topline results from the pivotal cohort of REMAIN-1 are expected in the fourth quarter.
A duodenal mucosal resurfacing procedure may help adults with obesity maintain weight loss 1 year after discontinuing obesity pharmacotherapy, according to topline results from the REMAIN-1 midpoint cohort.
The Revita (Fractyl Health) duodenal mucosal resurfacing (DMR) system is an endoscopic procedure that remodels duodenal lining to restore healthy nutrient sensing and signaling disrupted by chronic metabolic disease, according to a press release from the company. As Healio previously reported from Digestive Disease Week, adults who underwent a sham procedure in the REMAIN-1 trial regained 40% more weight after GLP-1 discontinuation than those who underwent DMR 6 months after stopping tirzepatide (Zepbound, Eli Lilly). New 1-year data released by the company revealed similar findings, with DMR reducing weight regain by approximately 40% compared with the sham procedure.
A duodenal mucosal resurfacing procedure allowed adults who discontinued tirzepatide to maintain most of their weight loss at 1 year. Image: Adobe Stock
The REMAIN-1 midpoint cohort included 45 adults who previously used tirzepatide and lost at least 15% of their body weight with the drug. After tirzepatide discontinuation, participants were randomly assigned, 2:1, to undergo DMR or a sham procedure.
At 1 year, the DMR group regained 7.8% of their body weight compared with 13% weight regain with the sham procedure.
Adults who received complete duodenal ablation of more than 14 cm with the intervention maintained about 81% of their weight loss with tirzepatide compared with 48% weight maintenance with the sham procedure. Among adults with complete duodenal ablation and weight loss with tirzepatide of at least 17.5%, weight loss maintenance was 84% with DMR compared with 46% with the sham procedure.
Of adults undergoing DMR, 73% maintained at least a 5% weight loss at 1 year compared with their weight before tirzepatide initiation.
There were no serious adverse events or device-related treatment-emergent adverse events between 6 months and 1 year. Treatment-emergent adverse events occurred among 24% of the DMR group vs. 25% of the sham group.
“The success of GLP-1 medicines has created a new unsolved problem: What happens when patients stop?” Harith Rajagopalan, MD, PhD, cofounder and CEO of Fractyl, said in a press release. “Most do stop eventually, whether because of cost, side effects or simply not wanting to inject a drug for the rest of their lives. When they stop, the weight most often comes back. [These] results are the first randomized, sham-controlled evidence that a single Revita procedure can keep most of the weight off for a full year after GLP-1 is stopped, without the need for ongoing medication.”
Topline results from the REMAIN-1 pivotal cohort are expected early in the fourth quarter.
Perspective
These results are intriguing because weight regain after discontinuing GLP-1-based therapy is a major clinical challenge. In this small randomized, sham-controlled midpoint cohort, Fractyl reported less average weight regain at 1 year after Revita. The apparent treatment effect was greatest in exploratory analyses of participants who received a longer, more complete duodenal ablation.
A one-time endoscopic intervention that preserves a substantial portion of medication-induced weight loss could eventually address an important treatment gap for patients who cannot or do not wish to continue long-term pharmacotherapy.
However, these findings should be considered hypothesis-generating rather than practice-changing. The cohort included only 45 participants and was not powered for formal statistical significance. The strongest results came from small subgroup analyses, making confirmation in the fully powered pivotal cohort essential. Peer-reviewed data are also needed on cardiometabolic outcomes, body composition, quality of life, procedural reproducibility, durability beyond 1 year and uncommon adverse events.
Importantly, these data should not encourage routine discontinuation of effective obesity medications. Obesity is a chronic disease, and continued pharmacotherapy remains appropriate for many patients. If validated, duodenal mucosal resurfacing may become another option within a personalized, long-term treatment strategy rather than a universal replacement for GLP-1 therapy.
Jerry Dang, MD, PhD, FRCSC, FACS, FASMBS
Disclosures: Dang reports no relevant financial disclosures.
Sources/Disclosures
Source:
Disclosures:
Rajagopalan reports being cofounder and CEO of Fractyl Health.
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