- |||||||||| Myalept (metreleptin) / Novelion
Review, Journal: Familial Partial Lipodystrophy (FPLD): Recent Insights. (Pubmed Central) - May 24, 2020
Preliminary data on the use of glucagon-like peptide 1 receptor agonists (GLP1 Ras) and sodium-glucose co-transporter 2 (SGLT2) inhibitors in cases of FPLD have shown promising results with reduction in total insulin requirements and improvement in glycemic control. Finally, investigational trials for new therapeutic agents in the management of FPLD are underway.
- |||||||||| Myalept (metreleptin) / Novelion
[VIRTUAL] Leptin Decreases De Novo Lipogenesis in Lipodystrophic Patients () - May 15, 2020 - Abstract #ENDOI2020ENDO-I_107;
These data indicate a strong link between metreleptin’s effects to increase clearance of blood glucose by peripheral tissues and reduce hepatic carbohydrate flux, resulting in DNL reductions. This led to lowered hepatic steatosis and dyslipidemia and suggests treatments that target multi-organ insulin resistance may lead to decreased NAFLD and cardiovascular risk.
- |||||||||| Myalept (metreleptin) / Novelion
Clinical, Journal: Thyroid abnormalities in patients with extreme insulin resistance syndromes. (Pubmed Central) - Apr 29, 2020
Patients with extreme insulin resistance due to lipodystrophy or insulin receptor mutations (INSR) are treated with high-dose insulin and recombinant leptin (metreleptin), which may increase the risk of thyroid neoplasia...Patients with homozygous INSR mutation had thyromegaly, which may be a novel phenotypic feature of this disease. Further studies are needed to determine the etiology of thyroid abnormalities in patients with extreme insulin resistance.
- |||||||||| Myalept (metreleptin) / Novelion
Clinical, Journal: Adherence with metreleptin therapy and health self-perception in patients with lipodystrophic syndromes. (Pubmed Central) - Apr 29, 2020
Further studies are needed to determine the etiology of thyroid abnormalities in patients with extreme insulin resistance. Metreleptin increases health self-perception and decreases morphotype-associated stigmatization in most patients with lipodystrophic syndromes, but poor comfort of use and local side effects weaken adherence.
- |||||||||| Myalept (metreleptin) / Novelion
Journal: Beneficial effects of leptin substitution on impaired eating behavior in lipodystrophy are sustained beyond 150 weeks of treatment. (Pubmed Central) - Feb 24, 2020
It is possible that some leptin-deficient patients (especially those who need primarily control of food intake) may still theoretically benefit from MC4R agonistic action, and further studies in carefully selected patients may help to tease out the differential pathways of metabolic regulation by the complex network of leptin signaling system. First evidence is presented that long-term metreleptin treatment of >150 weeks has sustained effects on eating behavior with increased satiety, as well as reduced hunger and hunger-related measures.
- |||||||||| Myalept (metreleptin) / Novelion
Congenital Leptin Deficiency: Clinical Insights from the First Reported US Cases (Room 157) - Feb 7, 2020 - Abstract #ENDO2020ENDO_3514;
Leptin deficiency should be considered in all patients with early onset obesity and hypothalamic amenorrhea. Furthermore, to our knowledge, this is the first report of lymphoma in a patient with CLD, occurring prior to any treatment with metreleptin.
- |||||||||| metformin / Generic mfg., Opdivo (nivolumab) / Ono Pharma, BMS
Acquired Generalized Lipodystrophy: A Rare Side Effect of PD1-Inhibitor Therapy (ENDOExpo) - Feb 7, 2020 - Abstract #ENDO2020ENDO_2534;
Of note, injecting insulin and use of a continuous glucose monitor have been a challenge given the lack of SAT. Although AGL resulting from PD1-inhibitor therapy is rare, it is a condition for which this patient will need life-long treatment.
- |||||||||| Myalept (metreleptin) / Novelion
Leptin Decreases De Novo Lipogenesis in Lipodystrophic Patients (Room 154) - Feb 7, 2020 - Abstract #ENDO2020ENDO_2018;
These data indicate a strong link between metreleptin's effects to increase clearance of blood glucose by peripheral tissues and reduce hepatic carbohydrate flux, resulting in DNL reductions. This led to lowered hepatic steatosis and dyslipidemia and suggests treatments that target multi-organ insulin resistance may lead to decreased NAFLD and cardiovascular risk.
- |||||||||| Myalept (metreleptin) / Novelion
Clinical, Journal, IO Biomarker: Metabolomic Analysis of the Effects of Leptin Replacement Therapy in Patients with Lipodystrophy. (Pubmed Central) - Feb 6, 2020
Our objective was to utilize metabolomic profiling to examine the changes associated with administration of short-term metreleptin therapy in patients with lipodystrophy...Leptin replacement therapy has significant effects on important metabolic pathways implicated in patients with lipodystrophy. Continued metabolomic studies may provide further insight into the mechanisms of action of leptin replacement therapy and provide novel biomarkers of lipodystrophy.Abbreviations: 1,5-AG, 1,5-anhydroglucitol; 11βHSD1, 11-β hydroxysteroid dehydrogenase 1; BCAA, branched-chain amino acid; FFA, free fatty acid; GC-MS, gas chromatography mass spectrometry; IDO, indoleamine 2,3-dioxygenase; IFN-γ, interferon-γ; m/z, mass to charge ratio; OGTT, oral glucose tolerance test; TDO, tryptophan 2,3-dioxygenase; TNF-α, tumor necrosis factor-α; UPLC-MS/MS, ultra-performance liquid chromatography-tandem mass spectrometry.
- |||||||||| Myalept (metreleptin) / Novelion
Trial completion: Effects of Leptin Replacement in Children (clinicaltrials.gov) - Jan 9, 2020
P2, N=1, Completed,
Continued metabolomic studies may provide further insight into the mechanisms of action of leptin replacement therapy and provide novel biomarkers of lipodystrophy.Abbreviations: 1,5-AG, 1,5-anhydroglucitol; 11βHSD1, 11-β hydroxysteroid dehydrogenase 1; BCAA, branched-chain amino acid; FFA, free fatty acid; GC-MS, gas chromatography mass spectrometry; IDO, indoleamine 2,3-dioxygenase; IFN-γ, interferon-γ; m/z, mass to charge ratio; OGTT, oral glucose tolerance test; TDO, tryptophan 2,3-dioxygenase; TNF-α, tumor necrosis factor-α; UPLC-MS/MS, ultra-performance liquid chromatography-tandem mass spectrometry. Active, not recruiting --> Completed
- |||||||||| Myalept (metreleptin) / Novelion
Trial completion: Effects of Human Leptin Replacement (clinicaltrials.gov) - Jan 9, 2020
P2, N=3, Completed,
Active, not recruiting --> Completed Active, not recruiting --> Completed
- |||||||||| Myalept (metreleptin) / Novelion
Enrollment change, Trial termination: Leptin in Human Energy and Neuroendocrine Homeostasis (clinicaltrials.gov) - Sep 18, 2019
P=N/A, N=22, Terminated,
N=60 --> 22 | Active, not recruiting --> Terminated; Closed by sponsor. Lack of funding.
- |||||||||| Myalept (metreleptin) / Novelion
Review, Journal: Update on Therapeutic Options in Lipodystrophy. (Pubmed Central) - Sep 12, 2019
Current treatment of generalized lipodystrophy includes metreleptin replacement as an adjunct to diet and standard treatment approach for metabolic consequences of lipodystrophy. Beyond metreleptin, a number of different compounds and treatment modalities are being studied for the treatment of partial lipodystrophy.
- |||||||||| Myalept (metreleptin) / Novelion
Enrollment status, Enrollment change: Effect of Metreleptin Therapy in the Treatment of Severe Insulin Resistance (clinicaltrials.gov) - Aug 30, 2019
P2, N=11, Enrolling by invitation,
Beyond metreleptin, a number of different compounds and treatment modalities are being studied for the treatment of partial lipodystrophy. Recruiting --> Enrolling by invitation | N=20 --> 11
- |||||||||| Symlin (pramlintide) / AstraZeneca
Trial completion date, Trial primary completion date, MRI: A Study of the Functional Magnetic Resonance Imaging Response to Leptin and Pramlintide (clinicaltrials.gov) - Aug 7, 2019
P=N/A, N=10, Active, not recruiting,
We suggest that these patients represent a potential subgroup of APL who may benefit from metreleptin or investigational therapies as standard treatment strategies fail to achieve a good metabolic control. Trial completion date: Jul 2012 --> Jul 2020 | Trial primary completion date: Jul 2012 --> Jul 2020
- |||||||||| Myalept (metreleptin) / Novelion
Clinical, Review, Journal, Adverse events: Clinical Trials Required to Assess Potential Benefits and Side Effects of Treatment of Patients With Anorexia Nervosa With Recombinant Human Leptin. (Pubmed Central) - Jun 4, 2019
...Over the past 20 years, such patients have been successfully treated with recombinant human (rh) leptin (metreleptin) within a compassionate use program...Furthermore, a potential dissection of hypoleptinemia-induced AN symptoms from the primary cognitions and behaviors of these patients could ensue. Accordingly, the aim of this article is to review the current state of the art of leptin in relation to AN to provide the theoretical basis for the initiation of clinical trials for treatment of this eating disorder.
- |||||||||| Myalept (metreleptin) / Novelion
Enrollment status: Compassionate Use of Metreleptin in Previously Treated People With Generalized Lipodystrophy (clinicaltrials.gov) - Jun 3, 2019
P3, N=30, Recruiting,
Accordingly, the aim of this article is to review the current state of the art of leptin in relation to AN to provide the theoretical basis for the initiation of clinical trials for treatment of this eating disorder. Enrolling by invitation --> Recruiting
- |||||||||| Myalept (metreleptin) / Novelion
Clinical, Journal: Effects of metreleptin on proteinuria in patients with lipodystrophy. (Pubmed Central) - Apr 18, 2019
The mechanisms leading to proteinuria in lipodystrophy and improvements in proteinuria with metreleptin are not clear. Hyperfiltration was also more common in GLD versus PLD but did not change with metreleptin.
- |||||||||| Myalept (metreleptin) / Novelion
Trial completion, Enrollment change, Trial completion date, Trial primary completion date: Short-term Effects of Leptin in People With Lipodystrophy (clinicaltrials.gov) - Feb 27, 2019
P2, N=27, Completed,
This entity is associated with diabetes with prominent insulin resistance and severe hypertriglycemia and can be successfully treated with metreleptin for the long term. Recruiting --> Completed | N=40 --> 27 | Trial completion date: Dec 2019 --> Feb 2018 | Trial primary completion date: Dec 2019 --> Feb 2018
- |||||||||| Myalept (metreleptin) / Novelion
Review, Journal: Lipodystrophies, dyslipidaemias and atherosclerotic cardiovascular disease. (Pubmed Central) - Feb 26, 2019
Patients with APL have a relatively low prevalence of hypertriglyceridaemia and diabetes mellitus. Overall, patients with lipodystrophies appear to be at high risk of ASCVD due to increased prevalence of dyslipidaemia and diabetes and efforts should be made to manage these metabolic complications aggressively to prevent ASCVD.
- |||||||||| Myalept (metreleptin) / Novelion
Trial primary completion date: Short-term Effects of Leptin in People With Lipodystrophy (clinicaltrials.gov) - Jan 29, 2019
P2, N=40, Recruiting,
Overall, patients with lipodystrophies appear to be at high risk of ASCVD due to increased prevalence of dyslipidaemia and diabetes and efforts should be made to manage these metabolic complications aggressively to prevent ASCVD. Trial primary completion date: Dec 2018 --> Dec 2019
- |||||||||| Review, Journal: Future Pharmacotherapy for Obesity: New Anti-obesity Drugs on the Horizon. (Pubmed Central) - Oct 4, 2018
This review focuses on anti-obesity drugs in the pipeline including centrally acting agents (setmelanotide, neuropeptide Y antagonist [velneperit], zonisamide-bupropion [Empatic], cannabinoid type-1 receptor blockers), gut hormones and incretin targets (new glucagon-like-peptide-1 [GLP-1] analogues [semaglutide and oral equivalents], amylin mimetics [davalintide, dual amylin and calcitonin receptor agonists], dual action GLP-1/glucagon receptor agonists [oxyntomodulin], triple agonists [tri-agonist 1706], peptide YY, leptin analogues [combination pramlintide-metreleptin]), and other novel targets (methionine aminopeptidase 2 inhibitor [beloranib], lipase inhibitor [cetilistat], triple monoamine reuptake inhibitor [tesofensine], fibroblast growth factor 21), including anti-obesity vaccines (ghrelin, somatostatin, adenovirus36). With these new drugs in development, anti-obesity therapeutics have potential to vastly expand allowing better treatment options and personalized approach to obesity care.
- |||||||||| Myalept (metreleptin) / Novelion
Trial primary completion date: Compassionate Use of Metreleptin in Previously Treated People With Partial Lipodystrophy (clinicaltrials.gov) - Aug 15, 2018
P3, N=30, Enrolling by invitation,
With these new drugs in development, anti-obesity therapeutics have potential to vastly expand allowing better treatment options and personalized approach to obesity care. Trial primary completion date: Jul 2018 --> Jul 2019
- |||||||||| Myalept (metreleptin) / Novelion
Review, Journal: Lipodystrophy Syndromes. (Pubmed Central) - May 8, 2018
The metabolic abnormalities associated with lipodystrophy include insulin resistance, hypertriglyceridemia, and hepatic steatosis. Management focuses on preventing and treating metabolic complications.
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