Supplemental Table 1: Anti-Diabetic and Lipid Lowering Medications Before and 1 Year after Initiation of Metreleptin

Transcription

1 Supplemental Table 1: Anti-Diabetic and Lipid Lowering Medications Before and 1 Year after Initiation of Metreleptin Total daily doses of anti-diabetic and lipid lowering medications are shown for each patient at baseline and 1 year on metreleptin. Gen=generalized lipodystrophy. Part=partial lipodystrophy. Patient Type of Lipodystrophy Baseline Diabetes Therapy 1 Year Diabetes Therapy Baseline Lipid Therapy 1 year Lipid Therapy 1 Gen Acarbose Orlistat 240 Plasmapheresis Gen Insulin 386 units 3 Gen Insulin 50 units 4 Gen Insulin 520 units 5 Gen Metformin 500 Metformin Gen Metformin Part Pioglitazone 15 Insulin 160 units Pioglitazone 30 Insulin 40 units Gen Rosiglitazone 8 Gen Pioglitazone 30 Insulin 270 units Insulin 150 units Gen Insulin 140 units 11 Gen Metformin Part Rosiglitazone 8 Glibenclamide 15 Rosiglitazone 8 Glibenclamide 15 Gen Fish oil 1000

2 14 Gen Insulin 120 units 15 Gen Insulin 64 units 16 Gen Insulin 200 units 145 Fish oil Fish oil Part Glibenclamide 10 Rosiglitazone 6 Simvastatin Simvastatin Part Metformin 1700 Rosiglitazone 8 Rosiglitazone 8 19 Gen Metformin 2550 Insulin 500 units Insulin 40 units Gen Metformin 2550 Insulin 520 units Part 160 Atorvastatin Atorvastatin 40 Niacin Gen Insulin 4000 units Insulin 2000 units 23 Part Metformin 2550 Metformin Gen Gen Insulin 190 units Atorvastatin Gen Insulin 290 units Insulin 60 units 160

3 28 Gen Insulin 300 units Insulin 60 units 29 Part Rosiglitazone 4 Glimepiride 3 Miglitol 300 Rosiglitazone 4 Glimepiride 6 Miglitol 300 Ciprofibrate 100 Ciprofibrate Gen 31 Gen 32 Part Metformin 1700 Insulin 700 units Metformin 1700 Insulin 1050 units 145 Ezetimibe 10 b 145 Ezetimibe 10 b 33 Gen Metformin 2500 Metformin Gen Metformin 500 Metformin 500 Fish oil Part Metformin 2550 Metformin Part Metformin 2550 Glibenclamide 10 Metformin 1700 Repaglinide Gen Insulin 400 units Insulin 250 units Part Metformin 2500 Insulin 300 units Metformin 2500 Insulin 300 units Part Insulin 300 units Insulin 160 units Ciprofibrate 100 Ciprofibrate 100 Atorvastatin Gen Insulin 600 units 1200

4 41 Part 42 Gen Metformin 2550 Insulin 75 units Metformin 2550 Insulin 150 units 43 Gen Insulin 12 units Gen Fish oil Part Metformin 1700 Insulin 590 units Metformin 1700 Insulin 57 units Fish oil Part Insulin 300 units Insulin 94 units 49 Part Repaglinide 2 Pioglitazone 15 Metformin Gen 51 Part Insulin 1700 units Insulin 500 units 52 Part Insulin 240 units 53 Gen Insulin 200 units 54 Gen Glipizide 5 55 Part Repaglinide 6 Pioglitzone Gen Insulin 180 units Metformin Part Acarbose 75 Insulin 70 units Repaglinide Atorvastatin Atorvastatin 40 Atorvastatin 40 Fish oil Simvastatin 5 145

5 58 Gen Metformin 2550 Insulin 35u nits 59 Gen Metformin Gen Metformin Part Insulin 400 units 62 Gen Insulin was stopped days before enrollment Insulin 184 units 64 Gen Insulin 310 units Insulin 120 units 65 Gen 67 Gen Insulin 7 units BID Fish oil Gen 69 Gen 70 Gen Metformin 1500 Metformin Part Insulin 80 units Insulin 60 units Atorvastatin 40 Niacin Part 74 Gen Insulin 72 units Metformin Atorvastatin 40 Niacin

6 75 Gen Insulin 170 units Insulin 200 units 76 Gen Metformin Gen Metformin, dose unknown 78 Part Metformin 1500 Metformin Part Metformin 2500 Insulin 220 units 81 Part Insulin 150 units Insulin 213 units Insulin 75 units 200 Atorvastatin 10 Fish oil 6000 Simvastatin Part Insulin 120 units Insulin 100 units 200 Atorvastatin 10 Simvastatin Gen Insulin 225 units Niacin 1500 Atorvastatin Gen Gen Insulin 420 units Gen Metformin 1700 Insulin 45 units 87 Part Saxagliptin 5 Insulin 230units 88 Gen Metformin 2500 Insulin 77 units Rosuvastatin 10 Ezetimibe Ezetimibe 10 54

7 89 Part Glipizide 20 Insulin 45 units Bydureon 2 /week Glipizide 20 Insulin 36 units Bydureon 2 /week Simvastatin 40 Simvastatin Part Insulin 375 units Insulin 345 units Part Glimepiride 4 Pioglitazone 30 Atorvastatin Gen Sitagliptin 200 Atorvastatin Gen 1200

8 Supplemental Table 2: Adverse Events among Lipodystrophy Patients Treated with Metreleptin Adverse events which occurred at least four times (~5% of patients) among lipodystrophy patients (generalized and partial lipodystrophy as one cohort) during 12 months of treatment with metreleptin. Data are number (percent of total number of events). Total number of events was 275. Infections included upper respiratory tract infections (3 patients), pneumonia (3), cellulitis (3), sinusitis (2) and urinary tract, adenoid, osteomyelitis, varicella reactivation, bacteremia, soft tissue abscess, ear infection, skin infection, appendicitis (1 patient). Benign tumors included breast lump (2 patients), and sciatic nerve tumor, ovarian mass, basal ganglia lesion, esophageal granular cell tumor (1 patient). Total number of serious adverse events was 21 occurring in 10 patients. SAEs= serious adverse events. Adverse Event Number of Number of Number of SAEs Events Patients Gastrointestinal 38 (14%) 33 (38%) 5 abdominal pain requiring hospitalization (1 patient) 1 acute exacerbation of pancreatitis Abdominal pain 15 (5%) 10 (12%) Nausea 9 (3%) 9 (10%) Constipation 5 (2%) 5 (6%) Diarrhea 5 (2%) 5 (6%) Decreased appetite 4 (1%) 4 (5%) Musculoskeletal 24 (9%) 19 (22%) Musculoskeletal pain 19 (7%) 15 (17%) Joint pain 5 (2%) 4 (5%) Infection 20 (7%) 13 (15%) 1 severe acute bronchitis 2 pneumonia (2 patients) 1 appendicitis 1 osteomyelitis 2 cellulitis (1 patient) 1 group B streptococcus bacteremia Mood-related 10 (4%) 10 (12%) Anxiety 6 (2%) 6 (7%) Depression 4 (1%) 4 (5%) Hematologic 11 (4%) 10 (12%) Anemia 6 (2%) 6 (7%) Iron deficiency 5 (2%) 4 (5%)

9 Other Hypoglycemia 12 (4%) 10 (12%) 5 exacerbations of heart failure (2 patients) 1 miscarriage 1 ovarian cyst requiring bilateral oophorectomy and total abdominal hysterectomy Weight loss 12 (4%) 12 (14%) Tumor, benign 6 (2%) 6 (7%) Fatigue 8 (3%) 7 (8%) Insomnia 5 (2%) 5 (6%) Headache 4 (1%) 4 (5%)