Table 1.

Inclusion and exclusion criteria

Inclusion criteria	Exclusion criteria
Age ≥ 18 years at the time of informed consent	Diagnosis of generalized lipodystrophy or acquired partial lipodystrophy (APL)
Clinical diagnosis of familial partial lipodystrophy plus diagnosis of type 2 diabetes mellitus and hypertriglyceridemia. Diagnosis of lipodystrophy is based on deficiency of subcutaneous body fat in a partial fashion assessed by physical examination and low skinfold thickness in the anterior thigh by caliper measurement: men (≤ 10 mm) and women (≤ 22 mm), and at least 1 of the following: • Genetic diagnosis of familial PL (e.g., mutations in LMNA, PPAR-γ, AKT2, CIDEC, PLIN1 genes) OR • Family history of FPLD or family history of abnormal and similar fat distribution plus 1 Minor Criteria OR 2 Minor Criteria (In the absence of FPLD-associated genetic variant or family history) and BMI< 35 kg/m2 MINOR Criteria a. Requirement for high doses of insulin, e.g., requiring ≥ 200 U/day, ≥ 2 U/kg/day, or currently taking U-500 insulin b. Presence of acanthosis nigricans on physical examination c. Evidence/history of polycystic ovary syndrome (PCOS) or PCOS-like symptoms (hirsutism, oligomenorrhea, and/or polycystic ovaries) d. History of pancreatitis associated with hypertriglyceridemia e. Evidence of non-alcoholic fatty liver disease • Hepatomegaly and/or elevated transaminases in the absence of a known cause of liver disease or radiographic evidence of hepatic steatosis (e.g., on ultrasound or CT)	Medical history of: • Recently diagnosed with acute pancreatitis (4 weeks from Screening) • acute or unstable cardiac ischemia (myocardial infarction, acute coronary syndrome, new-onset angina), stroke, transient ischemic attack (6 months from screening) • major surgery within 3 months of Screening • History of heart failure with New York Heart Association functional classification (NYHA) greater than Class II • Uncontrolled hypertension (blood pressure [BP] > 160 mm Hg systolic and/or 100 mm Hg diastolic) • History of bleeding diathesis or coagulopathy or clinically significant abnormality in coagulation parameters at Screening • Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed before Study Day 1 • Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C or chronic hepatitis B • Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated
Presence of diabetes mellitus associated with lipodystrophy [Hemoglobin (Hb) A1c ≥ 7 % and ≤ 12 %]	Clinically significant abnormalities in screening laboratory values that would render a subject unsuitable for inclusion, including the following: • Urine protein/creatinine ratio (UPCR) ≥ 0.25 mg/mg. • Estimated GFR ˂ 60 mL/min/1.73 m2 • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2x ULN • Bilirubin > ULN • Alkaline phosphatase (ALP) > 1.5 X ULN • Platelet count ˂ LLN
Elevated fasting plasma triglycerides (≥ 500 mg/dL or ≥ 5.7 mmol/L)	Use of metreleptin or anti-obesity drugs within 3 months before screening, GLP-1 agonists or systemic corticosteroids or anabolic steroids within 4 weeks before screening
Presence of hepatosteatosis (fatty liver), as evidenced by a Screening MRI indicating a hepatic fat fraction (HFF) ≥ 6.4 %	History within 6 months of Screening of drug or alcohol abuse
Willing to maintain their customary physical activity level and to follow a diet moderate in carbohydrates and fats with a focus on complex carbohydrates and to replace saturated for unsaturated fats	Unwilling to comply with lifestyle requirements
Provided written informed consent

GFR Glomerular filtration rate, ULN Upper limit of normality, LLN Lower limit of normality