TY - JOUR
T1 - Orlistat Therapy for Children with Type 1 Hyperlipoproteinemia
T2 - A Randomized Clinical Trial
AU - Patni, Nivedita
AU - Quittner, Claudia
AU - Garg, Abhimanyu
N1 - Funding Information:
Financial Support: This work was supported by South-western Medical Foundation and Center for Translational Medicine Grant UL1 TR001105. N.P. is a recipient of a “Friends of the Center for Human Nutrition Fellow” award from the UT Southwestern Medical Center.
PY - 2018/6/1
Y1 - 2018/6/1
N2 - Context Patients with type 1 hyperlipoproteinemia (T1HLP), a rare genetic disorder, have extreme chylomicronemia and recurrent episodes of acute pancreatitis. Currently, the only therapeutic option is to consume an extremely low-fat diet because the triglyceride-lowering medications are not efficacious. Objective To determine the efficacy of orlistat, a gastric and pancreatic lipase inhibitor, in reducing serum triglyceride levels in patients with T1HLP. Design and Setting We conducted a randomized, open-label, clinical trial with a four-period, two-sequence ("orlistat" and "off orlistat" for 3 months), crossover study design. Patients Two unrelated young Asian Indian males (11 and 9 years old) with T1HLP due to homozygous large GPIHBP1 deletions were enrolled at the UT Southwestern Medical Center. The patients were randomized to receive 3 months of orlistat or no therapy (off), then crossed over to the other arm, and this sequence was then repeated. Fasting serum triglyceride levels, fat-soluble vitamins, and gastrointestinal side effects were assessed. Results Compared with the two off periods, orlistat therapy reduced serum triglycerides by 53.3% and 53.0% in patient 1 and 45.8% and 62.2% in patient 2. There was no deficiency of fat-soluble vitamin levels, and their growth continued. There were no serious adverse effects of orlistat; patient 1 had a mild increase in passage of gas and bloating, and patient 2 had constipation with mild stool leakage. Conclusion Orlistat is safe and highly efficacious in lowering serum triglycerides in children with T1HLP and should be the first-line therapy in conjunction with an extremely low-fat diet.
AB - Context Patients with type 1 hyperlipoproteinemia (T1HLP), a rare genetic disorder, have extreme chylomicronemia and recurrent episodes of acute pancreatitis. Currently, the only therapeutic option is to consume an extremely low-fat diet because the triglyceride-lowering medications are not efficacious. Objective To determine the efficacy of orlistat, a gastric and pancreatic lipase inhibitor, in reducing serum triglyceride levels in patients with T1HLP. Design and Setting We conducted a randomized, open-label, clinical trial with a four-period, two-sequence ("orlistat" and "off orlistat" for 3 months), crossover study design. Patients Two unrelated young Asian Indian males (11 and 9 years old) with T1HLP due to homozygous large GPIHBP1 deletions were enrolled at the UT Southwestern Medical Center. The patients were randomized to receive 3 months of orlistat or no therapy (off), then crossed over to the other arm, and this sequence was then repeated. Fasting serum triglyceride levels, fat-soluble vitamins, and gastrointestinal side effects were assessed. Results Compared with the two off periods, orlistat therapy reduced serum triglycerides by 53.3% and 53.0% in patient 1 and 45.8% and 62.2% in patient 2. There was no deficiency of fat-soluble vitamin levels, and their growth continued. There were no serious adverse effects of orlistat; patient 1 had a mild increase in passage of gas and bloating, and patient 2 had constipation with mild stool leakage. Conclusion Orlistat is safe and highly efficacious in lowering serum triglycerides in children with T1HLP and should be the first-line therapy in conjunction with an extremely low-fat diet.
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U2 - 10.1210/jc.2018-00369
DO - 10.1210/jc.2018-00369
M3 - Article
C2 - 29659879
AN - SCOPUS:85048672428
VL - 103
SP - 2403
EP - 2407
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 6
ER -