Long Term Efficacy and Safety of Orlistat for Type 1 Hyperlipoproteinemia

* Type I hyperlipoproteinemia confirmed by bi-allelic disease-causing variants in any one of the T1HLP genes (LPL, APOC2, APOA5, LMF1, GPIHBP1, or GCKR). * Subjects who have a fasting TG greater than or equal to 750 mg/dL at the end of run-in period of 8 weeks will be eligible for randomization. * Age ≥ 8 years * Well controlled diabetes mellitus with hemoglobin A1c \< 8% * Off orlistat for a period of 2 months Exclusion Criteria: * Secondary hypertriglyceridemia due to diabetes, renal disease, , alcoholism and drug therapy such as estrogens and estrogen analogues, steroids, HIV-1 protease inhibitors, retinoic acid derivatives, interferons, or lasparaginase. * On lomitapide or participating in clinical trial of volanesorsen and olezarsen * On cyclosporine * Having serum TSH outside of the normal range if on levothyroxine supplementation. * Use of levothyroxine to suppress TSH in individuals with thyroid cancer. * Pregnant or lactating women * Significant liver disease (elevated transaminases \> 2 times upper limit of normal) * Alcohol abuse (\> 7 drinks or 84 g per week for women and \> 14 drinks or 168 g per week for men) * Severe anemia (hematocrit \< 24%) * Illicit drug use (cocaine, marijuana, LSD, etc.) * Major surgery in the past three months * Congestive heart failure * Serum creatinine greater than 2.5 mg/dL * Cancer within the past five years * Gastrointestinal surgery in the past * Current therapy with anti-coagulants, digoxin and anti-arrhythmics * Chronic malabs…