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Metreleptin

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https://www.readbyqxmd.com/read/29723161/metreleptin-improves-insulin-sensitivity-independent-of-food-intake-in-humans-with-lipodystrophy
#1
Rebecca J Brown, Areli Valencia, Megan Startzell, Elaine Cochran, Peter J Walter, H Martin Garraffo, Hongyi Cai, Ahmed M Gharib, Ronald Ouwerkerk, Amber B Courville, Shanna Bernstein, Robert J Brychta, Kong Y Chen, Mary Walter, Sungyoung Auh, Phillip Gorden
BACKGROUND: Recombinant leptin (metreleptin) ameliorates hyperphagia and metabolic abnormalities in leptin-deficient humans with lipodystrophy. We aimed to determine whether metreleptin improves glucose and lipid metabolism in humans when food intake is held constant. METHODS: Patients with lipodystrophy were hospitalized for 19 days with food intake held constant by controlled diet in an inpatient metabolic ward. In a non-randomized cross-over design, previously metreleptin-treated patients (n= 8) were continued on-metreleptin for five days, and off-metreleptin for the next 14 days (withdrawal cohort)...
May 3, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29704234/diagnosis-and-treatment-of-lipodystrophy-a-step-by-step-approach
#2
D Araújo-Vilar, F Santini
AIM: Lipodystrophy syndromes are rare heterogeneous disorders characterized by deficiency of adipose tissue, usually a decrease in leptin levels and, frequently, severe metabolic abnormalities including diabetes mellitus and dyslipidemia. PURPOSE: To describe the clinical presentation of known types of lipodystrophy, and suggest specific steps to recognize, diagnose and treat lipodystrophy in the clinical setting. METHODS: Based on literature and in our own experience, we propose a stepwise approach for diagnosis of the different subtypes of rare lipodystrophy syndromes, describing its more frequent co-morbidities and establishing the therapeutical approach...
April 27, 2018: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/29644599/long-term-effectiveness-and-safety-of-metreleptin-in-the-treatment-of-patients-with-generalized-lipodystrophy
#3
Rebecca J Brown, Elif A Oral, Elaine Cochran, David Araújo-Vilar, David B Savage, Alison Long, Gregory Fine, Taylor Salinardi, Phillip Gorden
PURPOSE: The purpose of this study is to summarize the effectiveness and safety of metreleptin in patients with congenital or acquired generalized lipodystrophy. METHODS: Patients (n = 66) aged ≥6 months had lipodystrophy, low circulating leptin, and ≥1 metabolic abnormality (diabetes mellitus, insulin resistance, or hypertriglyceridemia). Metreleptin dose (once or twice daily) was titrated to a mean dose of 0.10 mg/kg/day with a maximum of 0.24 mg/kg/day...
June 2018: Endocrine
https://www.readbyqxmd.com/read/29504049/future-pharmacotherapy-for-obesity-new-anti-obesity-drugs-on-the-horizon
#4
REVIEW
Gitanjali Srivastava, Caroline Apovian
PURPOSE OF REVIEW: Obesity is a global health crisis with detrimental effects on all organ systems leading to worsening disease state and rising costs of care. Persons with obesity failing lifestyle therapies need to be escalated to appropriate pharmacological treatment modalities, medical devices, and/or bariatric surgery if criteria are met and more aggressive intervention is needed. The progression of severe obesity in the patient population coupled with related co-morbidities necessitates the development of novel therapies for the treatment of obesity...
June 2018: Current Obesity Reports
https://www.readbyqxmd.com/read/29367704/association-of-metreleptin-treatment-and-dietary-intervention-with-neurological-outcomes-in-celia-s-encephalopathy
#5
David Araújo-Vilar, Rosario Domingo-Jiménez, Álvaro Ruibal, Pablo Aguiar, Salvador Ibáñez-Micó, Miguel Garrido-Pumar, Miguel Ángel Martínez-Olmos, Concepción López-Soler, Cristina Guillín-Amarelle, María González-Rodríguez, Antonio Rodríguez-Núñez, Julián Álvarez-Escudero, Mercedes Liñares-Paz, Blanca González-Méndez, Silvia Rodríguez-García, Sofía Sánchez-Iglesias
Celia's encephalopathy (progressive encephalopathy with/without lipodystrophy, PELD) is a recessive neurodegenerative disease that is fatal in childhood. It is caused by a c.985C>T variant in the BSCL2/seipin gene that results in an aberrant seipin protein. We evaluated neurological development before and during treatment with human recombinant leptin (metreleptin) plus a dietary intervention rich in polyunsaturated fatty acids (PUFA) in the only living patient. A 7 years and 10 months old girl affected by PELD was treated at age 3 years with metreleptin, adding at age 6 omega-3 fatty acid supplementation...
January 24, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29367426/leptin-replacement-reestablishes-brain-insulin-action-in-the-hypothalamus-in-congenital-leptin-deficiency
#6
Sabine Frank-Podlech, Julia von Schnurbein, Ralf Veit, Martin Heni, Jürgen Machann, Jaana M Heinze, Stephanie Kullmann, Jaida Manzoor, Saqib Mahmood, Hans-Ulrich Häring, Hubert Preissl, Martin Wabitsch, Andreas Fritsche
OBJECTIVE: Human obesity is associated with impaired central insulin signaling, and in very rare cases, severe obesity can be caused by congenital leptin deficiency. In such patients, leptin replacement results in substantial weight loss and improvement in peripheral metabolism. RESEARCH DESIGN AND METHODS: In a leptin-deficient patient, we investigated the impact of leptin substitution on central insulin action, as quantified by changes in neuronal activity after intranasal insulin application...
April 2018: Diabetes Care
https://www.readbyqxmd.com/read/28993984/facial-soft-tissue-volume-decreases-during-metreleptin-treatment-in-patients-with-partial-and-generalized-lipodystrophy
#7
Konstanze Miehle, Michael Stumvoll, Mathias Fasshauer, Thomas Hierl
PURPOSE: Lipodystrophy (LD) patients suffer from loss or maldistribution of subcutaneous adipose tissue accompanied by dysregulation of several adipocyte-secreted factors, e.g., leptin. The effect of recombinant leptin (metreleptin) therapy on facial soft tissue volume in patients with non-human immunodeficiency virus LD has not been quantified to date. METHODS: Eight LD patients (six female, two male; six familial partial LD [FPLD], two generalized LD) were treated with metreleptin over 1 year...
November 2017: Endocrine
https://www.readbyqxmd.com/read/28895299/case-of-lipoatrophic-diabetes-induced-by-juvenile-dermatomyositis
#8
Yusuke Baba, Hiyori Kaneko, Minoru Takemoto, Kana Ide, Yuki Haga, Tatsuo Kanda, Shinsuke Akita, Yoshitaka Kubota, Masayuki Kuroda, Yutaka Kitagawa, Koutaro Yokote
Lipodystrophy is a rare condition that is often accompanied by one or more metabolic diseases. Here, we report a case of lipoatrophic diabetes induced by juvenile dermatomyositis. Although pioglitazone was not effective for lowering blood glucose levels, our observation suggested that it improved liver function slightly. The effectiveness of metreleptin for lowering blood glucose levels could not be determined, as we administered it in a short period. Liver biopsy showed burned-out non-alcoholic steatohepatitis...
September 12, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28502512/metreleptin-therapy-lowers-plasma-angiopoietin-like-protein-3-in-patients-with-generalized-lipodystrophy
#9
Ranganath Muniyappa, Brent S Abel, Asha Asthana, Mary F Walter, Elaine K Cochran, Alan T Remaley, Monica C Skarulis, Phillip Gorden, Rebecca J Brown
BACKGROUND: Reduced triglyceride clearance due to impaired lipoprotein lipase-mediated lipolysis contributes to severe hypertriglyceridemia in lipodystrophy. Angiopoietin-like protein 3 (ANGPTL3) and 4 (ANGPTL4) impair clearance of triglycerides by inhibiting lipoprotein lipase. Whether circulating ANGPTL3/4 levels are altered in lipodystrophy and the effects of leptin replacement on these ANGPTLs are unknown. OBJECTIVE: To examine if ANGPTL3/4 levels are elevated in patients with generalized lipodystrophy and assess the effects of leptin replacement on these ANGPTLs...
March 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28324110/effects-of-metreleptin-in-pediatric-patients-with-lipodystrophy
#10
Rebecca J Brown, Cristina Adelia Meehan, Elaine Cochran, Kristina I Rother, David E Kleiner, Mary Walter, Phillip Gorden
Context: Lipodystrophy syndromes are rare disorders of deficient adipose tissue. Metreleptin, a human analog of leptin, improved metabolic abnormalities in mixed cohorts of children and adults with lipodystrophy and low leptin. Objective: Determine effects of metreleptin on diabetes, hyperlipidemia, nonalcoholic fatty liver disease (NAFLD), growth, and puberty in pediatric patients with lipodystrophy and low leptin. Design: Prospective, single-arm, open-label studies with continuous enrollment since 2000...
May 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28245771/current-drug-targets-in-obesity-pharmacotherapy-a-review
#11
REVIEW
Sangeeta P Bhat, Arun Sharma
Obesity, an impending global pandemic, is not being effectively controlled by current measures such as lifestyle modifications, bariatric surgery or available medications. Its toll on health and economy compels us to look for more effective measures. Fortunately, the advances in biology and molecular technology have been in our favour for delineating new pathways in the pathophysiology of obesity and have led to subsequent development of new drug targets. Development of antiobesity drugs has often been riddled with problems in the past...
2017: Current Drug Targets
https://www.readbyqxmd.com/read/28223297/efficacy-and-safety-of-metreleptin-therapy-in-patients-with-type-1-diabetes-a-pilot-study
#12
Chandna Vasandani, Gregory O Clark, Beverley Adams-Huet, Claudia Quittner, Abhimanyu Garg
OBJECTIVE: To study the efficacy and safety of metreleptin therapy in patients with suboptimally controlled type 1 diabetes mellitus (T1DM). RESEARCH DESIGN AND METHODS: After a baseline period of 4 weeks, five female and three male patients with T1DM (mean age 33 years, BMI 23.8 kg/m2 ) received metreleptin (0.08 mg/kg/day in females and 0.04 mg/kg/day in males) subcutaneously twice daily for 20 weeks followed by an off-therapy period of 4 weeks. RESULTS: Metreleptin therapy did not lower HbA1c significantly compared with the baseline value (mean difference -0...
May 2017: Diabetes Care
https://www.readbyqxmd.com/read/28007844/measurement-of-immunofunctional-leptin-to-detect-and-monitor-patients-with-functional-leptin-deficiency
#13
Martin Wabitsch, Lutz Pridzun, Michael Ranke, Julia von Schnurbein, Anja Moss, Stephanie Brandt, Katja Kohlsdorf, Barbara Moepps, Michael Schaab, Jan-Bernd Funcke, Peter Gierschik, Pamela Fischer-Posovszky, Bertram Flehmig, Jürgen Kratzsch
CONTEXT AND AIMS: Functional leptin deficiency is characterized by high levels of circulating immunoreactive leptin (irLep), but a reduced bioactivity of the hormone due to defective receptor binding. As a result of the fact that affected patients can be successfully treated with metreleptin, it was aimed to develop and validate a diagnostic tool to detect functional leptin deficiency. METHODS: An immunoassay capable of recognizing the functionally relevant receptor-binding complex with leptin was developed (bioLep)...
March 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/27967300/clinical-features-and-management-of-non-hiv-related-lipodystrophy-in-children-a-systematic-review
#14
Nidhi Gupta, Noor Asi, Wigdan Farah, Jehad Almasri, Patricia Barrionuevo, Mouaz Alsawas, Zhen Wang, Morey W Haymond, Rebecca J Brown, M Hassan Murad
Context: Lipodystrophy syndromes are characterized by generalized or partial absence of adipose tissue. Objective: We conducted a systematic review to synthesize data on clinical and metabolic features of lipodystrophy (age at onset, < 18 years). Data Source: Sources included Medline, Embase, Cochrane Library, Scopus and Non-Indexed Citations from inception through January 2016. Study Selection: Search terms included lipodystrophy, and age 0 to 18 years...
February 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27766009/cardiac-manifestations-of-congenital-generalized-lipodystrophy
#15
Vani P Sanon, Yehuda Handelsman, Son V Pham, Robert Chilton
IN BRIEF Congenital lipodystrophy is a rare genetic disorder characterized by a near-complete absence of fat cells, hypoleptinemia leading to a voracious appetite, and marked insulin resistance. This article focuses on the known cardiovascular manifestations of patients with congenital lipodystrophy, including cardiomyopathy, cardiac arrhythmias, and accelerated atherosclerosis arising from a markedly deranged metabolic milieu. Future research that targets leptin deficiency (metreleptin) and apoC3 mRNA (antisense oligonucleotide) could open a window for potential pharmacological treatment of this challenging disorder...
October 2016: Clinical Diabetes: a Publication of the American Diabetes Association
https://www.readbyqxmd.com/read/27710244/the-diagnosis-and-management-of-lipodystrophy-syndromes-a-multi-society-practice-guideline
#16
REVIEW
Rebecca J Brown, David Araujo-Vilar, Pik To Cheung, David Dunger, Abhimanyu Garg, Michelle Jack, Lucy Mungai, Elif A Oral, Nivedita Patni, Kristina I Rother, Julia von Schnurbein, Ekaterina Sorkina, Takara Stanley, Corinne Vigouroux, Martin Wabitsch, Rachel Williams, Tohru Yorifuji
OBJECTIVE: Lipodystrophy syndromes are extremely rare disorders of deficient body fat associated with potentially serious metabolic complications, including diabetes, hypertriglyceridemia, and steatohepatitis. Due to their rarity, most clinicians are not familiar with their diagnosis and management. This practice guideline summarizes the diagnosis and management of lipodystrophy syndromes not associated with HIV or injectable drugs. PARTICIPANTS: Seventeen participants were nominated by worldwide endocrine societies or selected by the committee as content experts...
December 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27642538/efficacy-and-safety-of-metreleptin-in-patients-with-partial-lipodystrophy-lessons-from-an-expanded-access-program
#17
Nevin Ajluni, Moahad Dar, John Xu, Adam H Neidert, Elif A Oral
OBJECTIVE: Patients with lipodystrophy have severe metabolic abnormalities (insulin resistance, diabetes, and hypertriglyceridemia) that may increase morbidity and mortality. Metreleptin is approved by the United States Food and Drug Administration for treatment of generalized forms of lipodystrophy. We aimed to determine the efficacy and safety of metreleptin among patients with partial lipodystrophy using an expanded-access model. METHODS: Study FHA101 (ClinicalTrials...
March 2016: Journal of Diabetes & Metabolism
https://www.readbyqxmd.com/read/27497155/progranulin-is-increased-in-human-and-murine-lipodystrophy
#18
COMPARATIVE STUDY
Konstanze Miehle, Thomas Ebert, Susan Kralisch, Annett Hoffmann, Jürgen Kratzsch, Haiko Schlögl, Michael Stumvoll, Mathias Fasshauer
AIMS: Lipodystrophies (LD) are genetic or acquired disorders sharing the symptom of partial or complete adipose tissue deficiency and a dysregulation of adipokines including leptin and adiponectin. Progranulin, an adipokine with proinflammatory and insulin resistance-inducing characteristics, has not been investigated in LD so far. METHODS: Circulating progranulin was determined in LD patients (N=37) and in age-, gender-, and body mass index-matched healthy control subjects (N=37)...
October 2016: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/27207511/leptin-substitution-in-patients-with-lipodystrophy-neural-correlates-for-long-term-success-in-the-normalization-of-eating-behavior
#19
RANDOMIZED CONTROLLED TRIAL
Haiko Schlögl, Karsten Müller, Annette Horstmann, Konstanze Miehle, Janett Püschel, Arno Villringer, Burkhard Pleger, Michael Stumvoll, Mathias Fasshauer
Lipodystrophy (LD) is a rare disease with a paucity of subcutaneous adipocytes and leptin deficiency. Patients often develop severe diabetes and, additionally, show a disturbed eating behavior with reduced satiety. The disturbed eating behavior can be restored by substitution with the leptin analog metreleptin. Long-term effects of metreleptin on resting state brain connectivity in treatment-naive patients with LD have not been assessed. In this study, resting state functional MRI scans and extensive behavioral testing assessing changes in hunger/satiety regulation were performed during the first 52 weeks of metreleptin treatment in nine patients with LD...
August 2016: Diabetes
https://www.readbyqxmd.com/read/27200503/leptin-administration-in-physiological-or-pharmacological-doses-does-not-alter-circulating-irisin-levels-in-humans
#20
RANDOMIZED CONTROLLED TRIAL
A Gavrieli, G Panagiotou, C S Mantzoros
Leptin is an adipokine causing browning of adipose tissue, and it thus increases energy expenditure. The same is true for irisin. We studied whether exogenously administered metreleptin affects serum irisin concentrations in humans, which would suggest a direct interplay between leptin and irisin. We performed two studies: a dose-escalating 1-day-long study and a randomized placebo-controlled study. Study 1: 15 healthy, normal-weight and/or obese male and female individuals participated in three 1-day-long trials of metreleptin administration in the fed state...
September 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
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