A pilot study of the effects of the somatostatin analog pasireotide in postoperative dumping syndrome.

Background Dumping syndrome is characterized by distinct pathophysiological features such as postprandial increase in hematocrit ( HT) and pulse rate ( PR) and delayed hypoglycemia ( HG). Treatment is based on dietary measures and somatostatin analogs ( SA), but current SAs have incomplete efficacy, possibly through limited affinity for various somatostatin receptor subtypes. We evaluated the effect of pasireotide, a novel SA with high affinity for 4/5 human somatostatin receptors, on pathophysiological events and symptoms in dumping. Methods Randomized double-blind placebo-controlled cross-over study of nine patients (six women, 47 ± 4 years) with postoperative dumping. Baseline measurements included oral glucose tolerance testing ( OGTT), abdominal ultrasound, and dumping symptom severity score ( DSSS). Patients were treated for 2 weeks with placebo or pasireotide 300 μg s.c. t.i.d. with a 1-week wash-out in a randomized fashion. On day 13 and 14 of each treatment OGTT, DSSS, and solid and liquid gastric emptying ( GE) were obtained. Key Results Baseline OGTT was pathological in all patients based on PR ( n = 5), HT ( n = 1) or HG ( n = 7). Compared to placebo, pasireotide suppressed the increase in PR (17.1 ± 2.8 vs 8.2 ± 3.5 bpm; p < 0.05) and late HG (nadir glycemia 55.6 ± 4.3 vs 83.3 ± 9.5 mg/dL; p = 0.007), increased peak glycemia (294.1 ± 33.3 vs 221.0 ± 23.1 mg/dL; p = 0.001) and delayed GE of solids (t1/2 83 ± 23 vs 43 ± 9 min; p = 0.05) and liquids (t1/2 70 ± 10 vs 40 ± 4 min, p = 0.05). The differences in DSSS did not reach statistical significance. Two patients dropped out because of adverse gastrointestinal events under pasireotide. Conclusions & Inferences Pasireotide affects pathophysiological features of both early and late dumping syndrome. [ABSTRACT FROM AUTHOR]