Myalept (metreleptin) / Novelion - LARVOL DELTA

Compassionate Use of Metreleptin in Previously Treated People With Generalized Lipodystrophy (clinicaltrials.gov) - P3 | N=30 | Recruiting | Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | Trial completion date: Jul 2025 ➔ Jul 2027 | Trial primary completion date: Jul 2025 ➔ Jul 2027

Trial completion date • Trial primary completion date • Diabetes • Dyslipidemia • Lipodystrophy • Metabolic Disorders

Compassionate Use of Metreleptin in Previously Treated People With Partial Lipodystrophy (clinicaltrials.gov) - P2 | N=29 | Active, not recruiting | Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | Trial completion date: Jul 2025 ➔ Jul 2027 | Trial primary completion date: Jul 2025 ➔ Jul 2027

Trial completion date • Trial primary completion date • Diabetes • Dyslipidemia • Lipodystrophy • Metabolic Disorders

Acquired Generalized Lipodystrophy Treated With Metreleptin in a Patient With Total Body Irradiation and Chronic Graft-Versus-Host Disease (ENDO 2025) - "The patient was treated with statin, fish oil, gemfibrozil, Humulin R U-500 insulin, insulin pump, pioglitazone, and multiple oral hypoglycemic agents, and her metabolic complications were refractory to these standard therapies. Childhood cancer survivors with a history of TBI and HSCT can develop acquired lipodystrophy with associated metabolic complications later in life. This case demonstrates the role of metreleptin in improving insulin sensitivity and lipoprotein profiles in a patient with AGL."

Clinical • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Diabetes • Dyslipidemia • Endocrine Disorders • Fibrosis • Graft versus Host Disease • Hematological Malignancies • Hepatology • Hypertriglyceridemia • Immunology • Lipodystrophy • Lymphoma • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Non-Hodgkin’s Lymphoma • Oncology • Pain • Rare Diseases • Severe Hypertriglyceridemia • Type 2 Diabetes Mellitus

Acquired Generalized Lipodystrophy Treated With Metreleptin in a Patient With Total Body Irradiation and Chronic Graft-Versus-Host Disease (ENDO 2025) - "The patient was treated with statin, fish oil, gemfibrozil, Humulin R U-500 insulin, insulin pump, pioglitazone, and multiple oral hypoglycemic agents, and her metabolic complications were refractory to these standard therapies. Childhood cancer survivors with a history of TBI and HSCT can develop acquired lipodystrophy with associated metabolic complications later in life. This case demonstrates the role of metreleptin in improving insulin sensitivity and lipoprotein profiles in a patient with AGL."

Clinical • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Diabetes • Dyslipidemia • Endocrine Disorders • Fibrosis • Graft versus Host Disease • Hematological Malignancies • Hepatology • Hypertriglyceridemia • Immunology • Lipodystrophy • Lymphoma • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Non-Hodgkin’s Lymphoma • Oncology • Pain • Rare Diseases • Severe Hypertriglyceridemia • Type 2 Diabetes Mellitus

Exploring MRI quantification techniques for phenotypes of adiposity: data from a clinical trial of metreleptin to treat Madelung's disease (ENDO 2025) - "Despite a difference between the average fat quantification from neck and thigh using MRI and DEXA, both methods show a strong correlation. Our data show a strong agreement between MRI and DEXA for neck fat quantification, but the same agreement was not seen in the thigh. Though preliminary, whole body MRI scans combined with ROI mapping can be utilized to determine precise fat quantification regionally and these methods can be useful during clinical trials testing impact of therapeutic agents on fat distribution."

Clinical • Lipodystrophy • Metabolic Disorders • Obesity • LEP

Resolving the Metabolic Puzzle, Tirzepatide's Multifaceted Benefits in Partial Lipodystrophy (ENDO 2025) - "Metreleptin is an approved therapy for GLD, but there are no FDA-approved treatments for PLD...Medications included insulin, metformin XR 2000 mg daily, empagliflozin 25 mg daily, rosuvastatin 20 mg daily, icosapent ethyl 4 grams daily, and fenofibrate 160 mg daily... The patient exhibited profound and multifaceted metabolic improvement following initiation of tirzepatide treatment. These improvements were much greater than previously reported with GLP-1 receptor agonists in PL, suggesting a unique role for GIP receptor agonism in addressing the complex metabolic dysregulation associated with this disorder. The observed clinical benefits, including improved glycemic control, triglyceride improvement, reduced insulin dependence, and improved steatosis have significant implications for the management of this complex and challenging condition."

Dyslipidemia • Genetic Disorders • Hepatology • Hypertriglyceridemia • Hypoglycemia • Lipodystrophy • Metabolic Disorders • Obesity • Obstructive Sleep Apnea • Pancreatitis • Respiratory Diseases • Sleep Apnea • Sleep Disorder

Decreased BCAA Levels in Lipodystrophy Patients Treated With Metreleptin (ENDO 2025) - "This latter finding supports IR as causal for elevations in BCAA. Mechanistically, these data are consistent with increased BCAA catabolism due to a leptin-induced increase in mammalian target of rapamycin complex 1 (mTORC1), an important complex in the catabolism of BCAA."

Clinical • Lipodystrophy • Metabolic Disorders • LEP

34-Year-Old Woman With Familial Partial Lipodystrophy Initially Suspected as Familial Hypertryglycerdiemia (ENDO 2025) - "Laboratory findings were notable for Elevated Hgb A1C (9.3%, n 3.9 - 5.6 %) , Normal C-peptide (1.3, n 0.5 - 3.3 ng/mL), glucose (83, n 74-109 mg/dl) normal, Glutamic Acid Decarboxylase Antibody (<5 IU/ml, n <5.0 IU/mL) normal, Triglycerides were very high (6,164 mg/dl, n 35 - 135 mg/dL), 17-Hydroxyprogesterone was normal ( 25.03 ng/dl), Anti-Mullerian Hormone was slightly elevated ( 5.021), IGF-1, (125 ng/ml collected at 33 years old, N 83-280 ng/ml), 1-mg dexamethasone suppression testing (<1.0 ug/dL), plasma metanephrines (<0.10 nmol/L, n 0.00 - 0.49 nmol/L), and prolactin (2.1 ng/ml, n 5.2 - 26.5 ng/mL) were all within the normal range...For hypertriglyceridemia patient was on fenofibrate 200 mg daily and Rosuvastatin 40 mg daily. Spironolactone 100 mg was prescribed for hirsutism...She was initially started on metformin for insulin resistance but developed intolerance due to gastrointestinal side effects... This is a rare case of familial partial..."

Clinical • Cardiovascular • Diabetes • Dyslipidemia • Gynecology • Hepatology • Hypertension • Hypertriglyceridemia • Lipodystrophy • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Pancreatitis • Polycystic Ovary Syndrome • Type 2 Diabetes Mellitus • IGF1 • LEP

Pharmacological Approaches in Lipodystrophy: Concomitant Medication and Metreleptin Therapy Use in the Participants of LD-Lync Study (ENDO 2025) - P | "Metformin was the most commonly used antidiabetic agent, particularly in FPLD (n=101), followed by CGL (n=21), APL (n=10), and AGL (n=5)...Fenofibrate was used by 79 patients, with the highest prevalence observed in the CGL (48%) and FPLD (35%) subgroups. Statins, primarily atorvastatin (n=57) and rosuvastatin (n=25), were the most prescribed lipid-lowering agents, and were used by 100 patients overall, including 47.9% of those in the FPLD subgroup...Omega-3 derivatives were used by 53 patients (19%), while niacin and cholestyramine were used by only two patients... This study highlights the heterogeneity in pharmacological management across lipodystrophy subtypes, reflecting their diverse metabolic profiles and needs. While metreleptin remains the cornerstone therapy for generalized lipodystrophy, there is a need for novel therapeutic options to achieve improved metabolic control and optimize treatment outcomes in partial lipodystrophy."

Dyslipidemia • Lipodystrophy • Metabolic Disorders • Rare Diseases

A real-world pharmacovigilance assessment and literature review of lymphoma development in lipodystrophy. (PubMed, Front Endocrinol (Lausanne)) - "While a contributory role for metreleptin in lymphoma development in patients with lipodystrophy cannot be excluded, our analysis suggests that lymphoma development may be associated with underlying pathophysiology that also leads to lipodystrophy rather than the pharmacological actions of metreleptin. Our findings support the view that, in some instances, immunoproliferative disorders of T-cells may contribute to syndromes involving autoimmune processes, including AGL."

Adverse events • Journal • Real-world evidence • Review • B Cell Lymphoma • Dermatomyositis • Hematological Malignancies • Hodgkin Lymphoma • Immunology • Leptin Receptor Deficiency Obesity • Lipodystrophy • Lymphoma • Metabolic Disorders • Myositis • Non-Hodgkin’s Lymphoma • Oncology • Rare Diseases • Solid Organ Transplantation • T Cell Non-Hodgkin Lymphoma • Transplantation • LEP

Attrition of adipose: Type 2 familial partial lipodystrophy manifesting in severe premature CAD (NLA 2025) - "She was prescribed icosapent ethyl and introduced to a lipodystrophy patient advocacy group...Metreleptin (recombinant leptin analog) is approved for severe generalized lipodystrophy and under investigation for partial lipodystrophy, while a similar leptin receptor agonist trial was terminated. LD expressed gratitude that knowing her diagnosis and connecting with others made her feel less alone and more supported. This case highlights the importance of considering lipodystrophy in the differential diagnosis of patients presenting with atypical features of classical metabolic syndrome and suggestive adipose distribution."

Cardiomyopathy • Cardiovascular • Coronary Artery Disease • Diabetes • Dyslipidemia • Hypertriglyceridemia • Lipodystrophy • Metabolic Disorders • Obesity • Pancreatitis • Severe Hypertriglyceridemia • Type 1 Diabetes Mellitus • LEP • LEPR • LMNA

One-year metreleptin in Colombian sisters with congenital leptin deficiency. (PubMed, Adipocyte) - "Limitations include the small sample size, absence of a control group, and lack of anti-metreleptin antibody measurements. Nevertheless, our findings support that leptin replacement with metreleptin is currently the only effective hormonal treatment for this monogenic form of human obesity."

Journal • Endocrine Disorders • Genetic Disorders • Leptin Receptor Deficiency Obesity • Obesity • LEP

METRAN: Metreleptin in Anorexia Nervosa (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Gabriella Milos | Trial completion date: Feb 2026 ➔ Aug 2026 | Trial primary completion date: Feb 2026 ➔ Aug 2026

Trial completion date • Trial primary completion date • Anorexia • CNS Disorders

Long-Acting Human PASylated Leptin Reaches the Murine Central Nervous System and Offers Potential for Optimized Replacement Therapy. (PubMed, Mol Pharm) - "Despite the multifaceted role of leptin for energy homeostasis and its broad therapeutic potential, the FDA/EMA-approved metreleptin constitutes the only leptin drug to date...However, discrete signals were observed in the hypothalamic region, only with leptin detectable in the choroid plexus, which implies cleavage of the PAS tag during transcytosis across the physiological barriers. This study should pave the way toward a second-generation leptin drug enabling prolonged dosing intervals."

Journal • Preclinical • Genetic Disorders • Leptin Receptor Deficiency Obesity • Obesity • LEP

Lipodystrophy in children following hematopoietic stem cell transplantation: analysis of prevalence, risk factors and response to conventional treatments (ESPE-ESE 2025) - "Our patient group consists of 2 males and 4 females, all of whom were diagnosed with leukemia in childhood. Patients 1, 2, and 4 were diagnosed within the first two years of life. Four of six patients underwent a total body irradiation (TBI) as pre-transplant conditioning and all of them had a history of cutaneous graft- versus-host-disease (GVHD)."

Clinical • Bone Marrow Transplantation • Diabetes • Dyslipidemia • Endocrine Disorders • Graft versus Host Disease • Hematological Malignancies • Hepatology • Immunology • Leukemia • Lipodystrophy • Metabolic Disorders • Oncology • Pediatrics • Transplantation • Type 2 Diabetes Mellitus • LEP

Diabetes Associated with Childhood Lipodystrophies: Clinical Characteristics and Management (ESPE-ESE 2025) - "The effective use of advanced diabetes technologies and targeted therapeutic strategies contributed to improvements in glycemic regulation. Keywords: Diabetes associated with lipodystrophy, Metabolic control, Insulin infusion pump, Metreleptin, Pediatric and adolescent diabetes"

Clinical • Diabetes • Lipodystrophy • Metabolic Disorders • Pain • Pediatrics • Renal Disease • Retinal Disorders

Leptin acutely increases hepatic triglyceride secretion in patients with lipodystrophy. (PubMed, Metabolism) - P2 | "Leptin acutely increases hepatic VLDL1-TG secretion in patients with lipodystrophy, likely contributing to metreleptin's body weight-independent anti-steatotic effects. The case report suggests that intact autonomic liver innervation may be required for this action, warranting further research."

Journal • Dyslipidemia • Hepatology • Lipodystrophy • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Transplantation • LEP

Natural History of Pregnancy and Pregnancy Outcomes in Metreleptin-Treated vs Untreated Subjects With Lipodystrophy (clinicaltrials.gov) - P=N/A | N=90 | Recruiting | Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | Trial completion date: Mar 2025 ➔ Mar 2026 | Trial primary completion date: Mar 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Lipodystrophy • Metabolic Disorders

A NOVEL THERAPY FOR FAMILIAL LIPODISTROPHY: A CASE REPORT OF UNUSUAL DIABETES MELLITUS (ATTD 2025) - "In Italy, Metreleptin became available for FPL patients in 2022, meeting specific criteria.Methods Diagnosis was confirmed through Next-generation sequencing (heterozygous PPARγ gene mutation). Despite conventional therapies (metformin, insulin and hypolipidemic agents), patient's glycemic control worsened, and experienced acute pancreatitis...JCEM 2019 Aug 1; 104(8):3068-3076. doi: 10.1210/jc.2018-02787"

Case report • Clinical • Diabetes • Dyslipidemia • Genetic Disorders • Hypertriglyceridemia • Lipodystrophy • Metabolic Disorders • Pancreatitis • LEP • LMNA • PPARG

Evaluation of Safety and Efficiency of Metreleptin Treatment for Patients With Multiple Symmetric Lipomatosis (MSL) (clinicaltrials.gov) - P2 | N=4 | Active, not recruiting | Sponsor: University of Michigan | Trial completion date: Apr 2025 ➔ Oct 2028

Trial completion date • Metabolic Disorders

Lipodystrophy Severity Score to Assess Disease Burden in Lipodystrophy. (PubMed, J Clin Endocrinol Metab) - "The LDS can reflect the severity of diverse manifestations of lipodystrophy and monitor changes following interventions."

Journal • Cardiovascular • Diabetes • Dyslipidemia • Lipodystrophy • Metabolic Disorders • Rare Diseases

Management of Obesity-Related Genetic Disorders. (PubMed, Endocrinol Metab Clin North Am) - "These disorders commonly impact systems such as the hypothalamic leptin-melanocortin signaling network, which plays a crucial role in controlling appetite and body weight, mainly through the melanocortin-4 receptor (MC4R) pathway. This review explores current management strategies and emerging therapies for genetic obesity disorders, highlighting the importance of treatment approaches and expanded genetic diagnostics to improve outcomes for affected individuals."

Journal • Review • Bardet–Biedl Syndrome • Genetic Disorders • Inherited Retinal Dystrophy • Obesity • Ophthalmology • Prader–Willi syndrome • LEP

Exploring the therapeutic potential of precision medicine in rare genetic obesity disorders: a scientific perspective. (PubMed, Front Nutr) - "Leptin deficiency is uniquely treated with recombinant human metreleptin, while those with LEPR, PCSK1, or POMC deficiency can now be treated with the MC4R agonist setmelanotide. This review highlights the most frequent monogenic and syndromic forms of obesity, and the future outlook of precision treatment for these conditions."

Journal • Review • Bardet–Biedl Syndrome • Genetic Disorders • Inherited Retinal Dystrophy • Leptin Receptor Deficiency Obesity • Obesity • Ophthalmology • POMC-null Obesity • LEP • PCSK1

Open-label Study to Evaluate Metreleptin in Children Under 6 Years of Age With Generalised Lipodystrophy (clinicaltrials.gov) - P3 | N=15 | Recruiting | Sponsor: Amryt Pharma | Initiation date: Jul 2024 ➔ Jan 2025

Trial initiation date • Diabetes • Dyslipidemia • Lipodystrophy • Metabolic Disorders

Adverse drug events associated with metreleptin administration: a real-world pharmacovigilance study from 2014 to 2024 using the FAERS database. (PubMed, Expert Opin Drug Saf) - "Overall TTO was 547 days (IQR: 113-1325), with Gastrointestinal disorders and investigations as hospitalization risk factors. This study provides critical insights into the TTO of ADEs related to metreleptin, informing safe clinical application and emphasizing the importance of monitoring potential side effects."

Adverse events • Journal • Real-world • Real-world evidence • Gastroenterology • Gastrointestinal Disorder