Impact of Leptin-Melanocortin Pathway Genetic Variants on Weight Loss Outcomes After Endoscopic Transoral Outlet Reduction

Variants in the leptin-melanocortin pathway (LMP) are associated with severe obesity. We evaluated weight loss of patients with or without heterozygous LMP variants, with weight recurrence after Roux-en-Y gastric bypass, who underwent endoscopic transoral outlet reduction (TORe).

We retrospectively reviewed patients genotyped for an LMP who had undergone TORe, classified as “carriers” or “non-carriers” of genetic variants.

We included 54 patients (22 carriers, 32 non-carriers). We identified 34 genetic variants in 21 different genes in 22 patients. Total body weight loss (%TBWL) after TORe was significantly different at 9 and 12 months (12 months: 0.68 ± 7.5% vs. 9.6 ± 8.2%, p < 0.01). This difference in weight loss was present even when analyzed in subgroups of patients who had undergone tubular TORe technique, and TORe plus APC. At 3, 6, and 12 months, the percentage of carriers achieving ≥ 5% and ≥ 10% TBWL was lower than non-carriers.

Patients with LMP variant who underwent RYGB had decreased weight loss 1 year after undergoing TORe.