Myalept (metreleptin) / Novelion - LARVOL DELTA

Acquired generalized lipodystrophy complicated by fulminant type 1 diabetes mellitus: a case report with review of literature and immunological insights. (PubMed, Endocr J) - "Although metreleptin therapy resulted in partial improvement in glycemic control, hemoglobin A1c (HbA1c) did not return to the pre-AGL level during follow-up. This case raises the possibility that persistent immune activation may contribute to insulin resistance beyond leptin deficiency in some patients with AGL."

Journal • Diabetes • Leptin Receptor Deficiency Obesity • Lipodystrophy • Metabolic Disorders • Rare Diseases • Type 1 Diabetes Mellitus • CD8 • IL2 • LEP

Lipodystrophies and female reproduction: pathophysiology, clinical spectrum, and management across the reproductive lifespan. (PubMed, Hormones (Athens)) - "Female reproductive dysfunction in lipodystrophy results from complex interactions between leptin, insulin, and gonadal steroid pathways. A multidisciplinary approach is required to optimize metabolic and reproductive outcomes, while prospective data on fertility and pregnancy under metreleptin remain crucial for future practice."

Journal • Review • Diabetes • Dyslipidemia • Endocrine Disorders • Gestational Diabetes • Gynecology • Hypertriglyceridemia • Infertility • Lipodystrophy • Metabolic Disorders • Pancreatitis • Polyendocrine Metabolic Ovarian Syndrome • Rare Diseases • Sexual Disorders • Women's Health • LEP

Lipodystrophy Severity Score Improves in Generalized Lipodystrophy Following Metreleptin Treatment (OBESITY WEEK 2026) - No abstract available

Lipodystrophy • Metabolic Disorders

Clinical heterogeneity and disease progression during adolescence in AGPAT2-associated congenital generalized lipodystrophy: a case series of four patients. (PubMed, J Pediatr Endocrinol Metab) - "These findings underscore the phenotypic variability of AGPAT2-associated CGL, the critical impact of puberty - especially in females - the frequent early onset of nephropathy, and the partial but incomplete response to leptin replacement. Close monitoring during adolescence and individualized management are essential."

Heterogeneity • Journal • Cardiovascular • Diabetes • Dyslipidemia • Fatigue • Hypertension • Hypertriglyceridemia • Lipodystrophy • Metabolic Disorders • Muscular Atrophy • Pediatrics • Renal Disease • Severe Hypertriglyceridemia • LEP

Metreleptin Therapy in Pediatric and Adult Patients with Congenital Leptin Deficiency: A Multicenter Real-World Experience (ESPE 2026) - No abstract available

Clinical • Real-world • Real-world evidence • Leptin Receptor Deficiency Obesity • Pediatrics • LEP

Metreleptin treatment of the first pediatric patient with Werner syndrome related familial partial lypodystrophy in Hungary (ESPE 2026) - No abstract available

Clinical • Late-breaking abstract • Metabolic Disorders • Pediatrics

Metabolic effects of Metreleptin in a child with lipodistrophy post-hematopoietic stem cell transplantation: toward a novel therapeutic paradigm (ESPE 2026) - No abstract available

Clinical • Bone Marrow Transplantation • Transplantation

A Study of the Safety of Mibavademab in Pediatric and Adult Participants Switching from Metreleptin to Mibavademab for the Treatment of Generalized Lipodystrophy (GLD) (clinicaltrialsregister.eu) - P3 | N=9 | Sponsor: Regeneron Pharmaceuticals Inc.

New P3 trial • Lipodystrophy • Metabolic Disorders • Pediatrics

Improvements in sleep, weight, and eating-disorder symptoms following off-label leptin treatment in an adolescent with chronic anorexia nervosa and insomnia: a case report. (PubMed, J Eat Disord) - "We report off-label administration of human recombinant leptin (metreleptin) over a 12-day period in a 17-year-old female adolescent with chronic anorexia nervosa (AN) and clinically significant insomnia...Over the longer-term window the course comprised continued substantial weight gain (BMI 18.3 kg/m² at d + 60), a marked drop in subjective insomnia, partial normalisation of circadian rhythm parameters in nonparametric analysis, and a transient increase in broader cognitive-affective symptoms. As a single retrospective case observation, the findings are hypothesis-generating and cannot be disentangled from concurrent weight gain and inpatient treatment."

Journal • Anorexia • CNS Disorders • Cognitive Disorders • Insomnia • Sleep Disorder • LEP

Expanded Access for Metreleptin for the Treatment of Diabetes Mellitus and/or Hypertriglyceridemia Associated With Lipodystrophy (clinicaltrials.gov) - P=N/A | N=0 | No Longer Available | Sponsor: Bristol-Myers Squibb | N=41 ➔ 0

Enrollment change • Diabetes • Dyslipidemia • Hypertriglyceridemia • Lipodystrophy • Metabolic Disorders

Classical phenylketonuria and partial lipodystrophy: an extremely rare and therapeutically challenging co occurrence (SSIEM 2026) - "Achieving weight reduction and optimal metabolic control is a central therapeutic aim, and advanced pharmacological options such as metreleptin and glucagon-like peptide-1 receptor agonists may provide substantial benefit; however, their catabolic effects risk further deterioration of metabolic control in PKU. Last, diet alone poses a particular challenge, requiring the careful integration of low-fat and low-protein intake within a phenylalanine-restricted regimen."

Bipolar Disorder • Cardiovascular • CNS Disorders • Diabetes • Dyslipidemia • Fibrosis • Genetic Disorders • Hepatology • Hypertension • Hypertriglyceridemia • Immunology • Lipodystrophy • Liver Cirrhosis • Metabolic Disorders • Mood Disorders • Obesity • Osteoporosis • Phenylketonuria • Rare Diseases • Severe Hypertriglyceridemia

Effect of metreleptin treatment in congenital generalized lipodystrophy: a retrospective analysis from the MENA region. (PubMed, J Endocrinol Invest) - "Our findings support early intervention with metreleptin for sustained diabetes and hypertriglyceridemia control in CGL."

Journal • Retrospective data • Diabetes • Dyslipidemia • Hypertriglyceridemia • Lipodystrophy • Metabolic Disorders • LEP

Unraveling the natural history of lipodystrophy syndromes: insights from the prospective LD-Lync study. (PubMed, J Endocr Soc) - P | "Eighty-one (30.4%) patients received at least one dose of metreleptin during clinical studies or commercially during follow-up. Our findings confirm that patients with lipodystrophy face a significant risk of comorbidities, with an earlier onset of diabetes, hypertriglyceridemia, and hepatic steatosis in those with GL compared to PL. This registry will serve as a crucial resource for gaining insights into the burden of disease in lipodystrophy."

Journal • Cardiovascular • Diabetes • Dyslipidemia • Fibrosis • Hypertension • Hypertriglyceridemia • Immunology • Lipodystrophy • Metabolic Disorders • Pancreatitis • Rare Diseases

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

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

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 | Completed | Sponsor: Regeneron Pharmaceuticals | Active, not recruiting ➔ Completed | Trial completion date: Nov 2026 ➔ Jul 2026

Trial completion • Trial completion date • Lipodystrophy • Metabolic Disorders • Pediatrics

Open-label Study to Evaluate Metreleptin in Children Under 6 Years of Age With Generalised Lipodystrophy (clinicaltrials.gov) - P3 | N=1 | Terminated | Sponsor: Amryt Pharma | N=15 ➔ 1 | Trial completion date: Sep 2026 ➔ Feb 2026 | Recruiting ➔ Terminated | Trial primary completion date: Sep 2026 ➔ Feb 2026; This clinical trial was closed early due to no longer being a requirement to the European Medicines Agency.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Diabetes • Dyslipidemia • Lipodystrophy • Metabolic Disorders

Hematopoietic stem cell transplantation-associated partial lipodystrophy. (PubMed, Clin Pediatr Endocrinol) - "There remains much to be clarified, including establishment of reliable diagnostic procedure, elucidation of long-term prognosis, and invention of effective treatment. Metreleptin is one of the promising options, and the accumulation of its therapeutic efficacy are warranted."

Journal • Review • Bone Marrow Transplantation • Diabetes • Graft versus Host Disease • Hypertriglyceridemia • Immunology • Lipodystrophy • Metabolic Disorders • Oncology • Sarcopenia • Transplantation

Tirzepatide in Congenital Generalized Lipodystrophy: A Case of Improved Glycemic Control in A Person with Severe Insulin Resistance (ENDO 2026) - "During adolescence, metreleptin therapy was initiated and titrated from 2.5 mg to 10 mg daily...Escalating doses of metformin, sitagliptin, and insulin degludec resulted in slight improvements in blood glucose, though the HbA1c remained persistently elevated at 10.5%. Following a trial of an SGLT-2 inhibitor, dapagliflozin, hematocrit was elevated (58%; normal 36–46%), which improved after drug cessation... This case demonstrates significant improvement in glycemic control with tirzepatide in a patient with congenital generalized lipodystrophy and severe insulin resistance, demonstrating its potential as an effective additional therapy in this patient."

Clinical • Cardiovascular • Diabetes • Dyslipidemia • Genetic Disorders • Hypertension • Hypertriglyceridemia • Lipodystrophy • Metabolic Disorders • Renal Disease

Comment on Korakas et al. 780G Hybrid Closed-Loop Pump as Adjunct to Metreleptin in Lipodystrophy-Associated Diabetes: Three Case Observations. (PubMed, Diabetes Care) - No abstract available

Journal • Diabetes • Lipodystrophy • Metabolic Disorders

Evaluating Pharmacological Treatments to Increase Bone Mineral Density in Functional Hypothalamic Amenorrhea: A Systematic Review and Network Meta-Analysis. (ENDO 2026) - "Finally, alendronate, metreleptin, and recombinant insulin-like growth factor 1 (IGF-1) were not effective at any skeletal site. Transdermal HRT and teriparatide both lead to clinically significant LS BMD improvements in women with FHA, while transdermal HRT also increases FN BMD. Conversely, oral HRT and COCP are not beneficial at any skeletal site. There are several likely mechanisms for the benefit of transdermal over oral estrogens, including differential effects on sex hormone binding globulin and osteoanabolic IGF-1."

Retrospective data • Review • Musculoskeletal Diseases • Orthopedics • Women's Health • IGF1

A 12-Month Randomized, Multicenter, Double-Blind, Placebo-Controlled Phase 3 Study to Evaluate the Safety and Efficacy of Metreleptin in Subjects with Partial Lipodystrophy: The METRE-PL Study (ENDO 2026) - P3 | "The baseline characteristics of the study population highlight the multi-systemic burden of disease and the need for effective management of the metabolic complications of FPLD. Trial results may support further therapeutic strategies for patients with this rare disease."

Clinical • P3 data • Diabetes • Diabetic Neuropathy • Dyslipidemia • Human Immunodeficiency Virus • Hypertriglyceridemia • Infectious Disease • Leptin Receptor Deficiency Obesity • Lipodystrophy • Metabolic Disorders • Pancreatitis • Rare Diseases • LEP

Real-World Prescribing Patterns of Combined Metreleptin and GLP-1 Receptor Agonist Therapy in Adults with Lipodystrophy (ENDO 2026) - "GLP-1RA therapy is used in combination with metreleptin in a substantial subset of patients with lipodystrophy in clinical practice. Patients receiving combination therapy had a high burden of metabolic comorbidities prior to GLP-1RA initiation, comparable to those receiving metreleptin alone. These real-world prescribing patterns highlight the need for prospective studies to evaluate the safety and efficacy of combination metreleptin/GLP-1RA therapy in patients with lipodystrophy."

Clinical • Real-world • Real-world evidence • Cardiovascular • Diabetes • Dyslipidemia • Hepatology • Hypertriglyceridemia • Leptin Receptor Deficiency Obesity • Lipodystrophy • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Pancreatitis • Type 2 Diabetes Mellitus • LEP

Metreleptin Reduces Circulating Branched-Chain Amino Acids Independent of Dietary Intake in Lipodystrophy (ENDO 2026) - "These findings suggest that short-term reductions in circulating BCAA with metreleptin occur independently of dietary BCAA intake and are linked to improvements in insulin resistance. The data support insulin resistance as a causal determinant of elevated circulating BCAA, consistent with altered BCAA metabolism rather than intake."

Leptin Receptor Deficiency Obesity • Lipodystrophy • Metabolic Disorders • LEP

Cancer Burden Across Lipodystrophy Subtypes: Results from the LD-Lync Study (ENDO 2026) - P | "Among patients receiving metreleptin, five cases of malignancy were identified across diverse LD subtypes: FPLD (n=2; skin cancer, renal cell carcinoma), AGL (n=2; medulloblastoma, lymphoma), and APL (n=1; breast cancer); two of which (skin and breast cancer) developed 2- and 6-years post-treatment, respectively, with no apparent association between cancer type and metreleptin exposure... Cancer prevalence in LD exceeded estimates for the 2025 U.S. general population (8.0% vs. ~5.4%), suggesting an increased malignancy burden not fully explained by age alone (U.S. median age ~38.5 years)."

Bone Marrow Transplantation • Brain Cancer • Breast Cancer • Genetic Disorders • Genito-urinary Cancer • Hematological Malignancies • Leukemia • Lipodystrophy • Lymphoma • Medulloblastoma • Metabolic Disorders • Oncology • Rare Diseases • Renal Cell Carcinoma • Skin Cancer • Solid Tumor

A 36-Month, Multicenter, Open Label Phase 4 Study to Evaluate the Immunogenicity of Daily Metreleptin Treatment in Patients with Generalized Lipodystrophy (ENDO 2026) - "NAb testing confirmed the greater sensitivity of the RB assay. The lack of a consistent association between ADA/NAb and treatment outcomes supports no new safety signals beyond existing knowledge and experience with metreleptin."

Clinical • P4 data • Lipodystrophy • Metabolic Disorders • Rare Diseases • LEP • LEPR