Myalept (metreleptin) / Novelion - LARVOL DELTA

Case Report: Metreleptin treatment enables successful pregnancy in a female with congenital generalized lipodystrophy. (PubMed, Front Endocrinol (Lausanne)) - "After 13 months of treatment with metreleptin the patient conceived spontaneously and delivered a healthy neonate. This rare and educational case indicates that metreleptin plays a key role in the adipose-mediated regulation of fertility."

Journal • Cardiovascular • Diabetes • Dyslipidemia • Lipodystrophy • Metabolic Disorders • LEP

Immunogenicity of Metreleptin in Patients With Generalized Lipodystrophy (clinicaltrials.gov) - P4 | N=11 | Completed | Sponsor: Aegerion Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed

Trial completion • Lipodystrophy • Metabolic Disorders

Advances of pharmacological therapies in lipodystrophy syndromes: current evidence and future directions. (PubMed, Expert Rev Endocrinol Metab) - "Dietary modification, exercise, lifestyle management, and metreleptin therapy are the mainstay of treatment, while conventional therapies are used to target specific complications...There is currently no cure for lipodystrophy syndromes. Emerging therapies are being investigated to expand therapeutic options and improve long-term outcomes of this complex disorder."

Journal • Review • Lipodystrophy • Metabolic Disorders • Rare Diseases

Epidemiological and Clinical Data from the European lipodystrophy (ECLip) registry. (PubMed, Eur J Endocrinol) - "This study describes the largest cohort of patients with lipodystrophy reported to date. The dataset offers a comprehensive view of the epidemiology, clinical presentation, and associated comorbidities of lipodystrophy."

Clinical data • Journal • Cardiovascular • Diabetes • Dyslipidemia • Human Immunodeficiency Virus • Infectious Disease • Lipodystrophy • Metabolic Disorders • Oncology • Rare Diseases • LMNA

Metreleptin In SHORT Syndrome With Uncontrolled Diabetes. (PubMed, JCEM Case Rep) - "This case highlights the potential utility of metreleptin in treating severe insulin resistance in SHORT syndrome, even in the absence of classical metabolic complications. Further studies are needed to define its role in atypical lipodystrophy syndromes with unusual metabolic phenotypes."

Journal • Diabetes • Dyslipidemia • Hypertriglyceridemia • Lipodystrophy • Metabolic Disorders • Type 1 Diabetes Mellitus • PIK3R1

Response to long-term pharmacological management of metreleptin in a patient with monogenic obesity due to mutation in the LEP gene. (PubMed, Cardiovasc Diabetol Endocrinol Rep) - "The patient achieved a reduction of 40 kg/m2 in BMI, corresponding to a body weight loss of 90 kg, with a significant improvement in associated metabolic comorbidities, acne, and hirsutism."

Journal • Acne Vulgaris • Genetic Disorders • Leptin Receptor Deficiency Obesity • Obesity • 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

METRE-PL: Study to Evaluate the Safety and Efficacy of Daily Subcutaneous Metreleptin Treatment in Subjects With PL (clinicaltrials.gov) - P3 | N=69 | Active, not recruiting | Sponsor: Amryt Pharma | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2026 ➔ Oct 2026 | Trial primary completion date: Jun 2025 ➔ Jul 2026

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

Long-Term Clinical Experience With Metreleptin in a Brazilian Patient With Congenital Generalized Lipodystrophy Type 2. (PubMed, JCEM Case Rep) - "At the most recent clinic evaluation (3 months after resuming metreleptin), HbA1c, triglycerides, and liver enzyme levels reduced relative to the last measurements taken during treatment interruption. These findings provide support for the long-term and continuous use of metreleptin in patients with generalized lipodystrophy."

Journal • Lipodystrophy • Metabolic Disorders

The clinical approach to child and adolescent patients with lipodystrophy: a series of international case discussions. (PubMed, Front Endocrinol (Lausanne)) - "The challenges faced by clinicians managing pediatric patients with lipodystrophy syndromes and how these challenges may differ from adult patients are also explored. The cases presented in this manuscript may assist clinical teams to promptly diagnose and holistically manage young patients with lipodystrophy syndromes and help optimize clinical outcomes as they transition to adult care."

Journal • Review • Endocrine Disorders • Lipodystrophy • Metabolic Disorders • Pediatrics • Rare Diseases • LEP

A Study of the Safety of Mibavademab in Pediatric and Adult Participants Switching From Metreleptin to Mibavademab for the Treatment of Generalized Lipodystrophy (GLD) (clinicaltrials.gov) - P3 | N=9 | Active, not recruiting | Sponsor: Regeneron Pharmaceuticals | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2027 ➔ Nov 2026 | Trial primary completion date: Mar 2027 ➔ Jul 2026

Enrollment closed • Trial completion date • Trial primary completion date • Lipodystrophy • Metabolic Disorders • Pediatrics

Dyslipidemias as rare diseases. (PubMed, Cas Lek Cesk) - "Thanks to new hypolipidemic drugs such as evinacumab and lomitapide, patients today have a much better prognosis than in the past...Due to new causal metreleptine therapy, we can help patients with managing these metabolic complications significantly...Therapy with volanesorsen leads to a reduction of hypertriglyceridemia, thereby reducing the risk of developing acute pancreatitis. Although these diseases are rare, it is necessary to think about them and diagnose them early. Interdisciplinary cooperation is essential during search and treatment of these patients."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Homozygous Familial Hypercholesterolemia • Hypertriglyceridemia • Lipodystrophy • Metabolic Disorders • Pancreatitis • Rare Diseases

Resolving the Metabolic Puzzle, Tirzepatide's Multifaceted Benefits in Partial Lipodystrophy (ENDO 2025) - "Both types lead to ectopic lipid deposition with resultant insulin resistance, and health consequences analogous to severe obesity despite low fat mass. 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..."

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

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

Severe Insulin Resistance in a Patient with Generalized Lipodystrophy (ENDO 2025) - "Her diabetes regimen included insulin degludec U-200 (76 units daily), insulin aspart (35 units with meals), and Trulicity (3 mg weekly)...She was started on metreleptin and discharged with insulin degludec U-200 (90 units twice daily), insulin aspart (60 units three times daily), tirzepatide (2.5 mg weekly), and empagliflozin (25 mg daily). Insulin resistance in lipodystrophy arises from the lack of functional adipose tissue, impairing the body's ability to store excess energy as fat...Metreleptin, along with dietary modifications, is the first-line treatment, improving insulin sensitivity, reducing nonalcoholic steatohepatitis, alleviating cardiac hypertrophy, and lowering mortality. Though rare, lipodystrophy requires early recognition for appropriate screening and treatment."

Clinical • Cardiovascular • Chronic Kidney Disease • Cushing’s Disease • Diabetes • Dyslipidemia • Endocrine Disorders • Hepatology • Lipodystrophy • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Nephrology • Renal Disease • Type 2 Diabetes Mellitus • LEP

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

Leptin- And Incretin-based Combination Therapy In Lipodystrophy: A Promising Metabolic Strategy? (ENDO 2025) - "Metreleptin (ML) remains the cornerstone of treatment for generalized lipodystrophy (GL); however, its efficacy in partial lipodystrophy (PL) can be limited, highlighting the need for alternative or incremental therapies to achieve optimal metabolic control...P3 (25-year-old, LMNA related GL (with T10I variant), treated with mibavademab for 4 years): after adding dulaglutide for 5 months, HbA1c reduced from 8.9% to 7.3%, with stable BMI (14.4 kg/m²) and no change in TG (265 to 273 mg/dL)...In summary, combined leptin-based and incretin-based therapies may enhance metabolic outcomes in lipodystrophy. Future randomized controlled trials are needed to evaluate the efficacy of incretin-based therapies either with or without leptin pathway treatments to confidently determine the extent of benefit of combination therapy in lipodystrophy."

Combination therapy • Late-breaking abstract • Lipodystrophy • Metabolic Disorders • Pancreatitis • Rare Diseases • LEP • LEPR • LMNA

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

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

Case report: Metreleptin rapidly improved anorexia nervosa related and comorbid psychopathology in a patient with high endogenous leptin levels adjusted for body mass index. (PubMed, Eur Child Adolesc Psychiatry) - "An insight into the mechanisms underlying this distinct type of leptin resistance may help to promote recovery of such affected patients. Placebo controlled randomized clinical trials are required to assess if and to what extent short and medium term metreleptin treatment indeed improves recovery."

Clinical • Journal • Anorexia • CNS Disorders • Depression • Major Depressive Disorder • Obsessive-Compulsive Disorder • Post-traumatic Stress Disorder • Psychiatry • LEP

Open-label Study to Evaluate Metreleptin in Patients With Partial Lipodystrophy (clinicaltrials.gov) - P4 | N=12 | Recruiting | Sponsor: Amryt Pharma | Trial completion date: Sep 2027 ➔ Feb 2028 | Trial primary completion date: Sep 2027 ➔ Feb 2028

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

The impact of neuregulin 4 on metabolic dysregulation in lipodystrophy. (PubMed, Endocrinology) - "Although metreleptin therapy has shown beneficial effects, its therapeutic efficacy is limited, particularly in patients with partial LD...Together, our data indicate that NRG4's beneficial effects may depend on the presence of functional adipose tissue, which is profoundly impaired in lipodystrophy. Consequently, while NRG4 may support local plasticity in adipose tissue, it is insufficient as a therapy for metabolic restoration in LD."

Journal • Lipodystrophy • Metabolic Disorders • Rare Diseases

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: Jan 2025 ➔ May 2025

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

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