Roux-en-Y gastric bypass (RYGB) induces large and sustained weight loss in most patients. However, a minority of patients (5-10%) never obtain a successful weight loss after RYGB. The aim of this study was to characterize the role of gut hormones for appetite regulation in patients with primary weight loss (WL) failure defined as maximal excess BMI loss (EBLmax= ΔBMIpreoperative-postoperative/ΔBMIpreoperative-25) <50% compared with patients with successful WL (EBLmax >60%) after RYGB. Twenty women with primary WL failure (EBL 24% [9;27], median [IQR]) were matched to 20 women with successful WL (EBL 74% [70;83]) on age (51±9 vs. 51±9 years, mean ± sd), preoperative BMI (43.1±4.0 vs. 43.0±3.6 kg/m2) and time from RYGB (4.8±2.0 vs. 4.8±1.4 years). On separate days, a patient blinded subcutaneous injection of the somatostatin analogue Octreotide (Oct) 1 µg/kg bodyweight (max 100 µg) or saline (placebo) was given in randomized order followed by a mixed meal test at T=30 min and an ad libitum meal with measurement of food intake at T=270 min. The WL failure group had similar GLP-1 (tAUC, median [IQR], 4039 [3336;6018] vs. 4669 [3006;5891] pM·min, p=0.30) and PYY secretion (tAUC, 1935 [1493;2783], 1778 [1163;2756] pM·min, p=0.65) on the placebo day compared with the successful WL group. Injection of Oct diminished GLP-1 and PYY secretion in both groups. Oct had no effect on ad libitum food intake in the WL failure group (-0.5% [-13, 12], mean [95% CI]), while food intake was increased after Oct in the successful WL group (+23% [1.6, 44]) (ANOVA Group x Oct p=0.04).

In conclusion, primary WL failure after RYGB was not explained by lower secretion of GLP-1 or PYY. However, inhibition of hormone secretion with octreotide increased food intake only in patients with successful WL, whereas the effect was absent in patients with primary WL failure. These results support that an impaired gut-hormone mediated suppression of appetite could contribute to primary weight loss failure after RYGB.


K.N. Bojsen-Moller: None. M.S. Svane: None. C. Martinussen: None. C. Dirksen: None. N.B. Jørgensen: Stock/Shareholder; Self; Novo Nordisk A/S. V. Kristiansen: None. B. Hartmann: None. J.J. Holst: Advisory Panel; Self; Novo Nordisk A/S. S. Madsbad: None.


Danish Council for Independent Research

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