Investigational Drug Details
| Drug ID: | D226 |
| Drug Name: | Metreleptin |
| Synonyms: | N-Methionylleptin; r-metHuLeptin |
| Type: | Biological drug |
| DrugBank ID: | DB09046 |
| DrugBank Description: | Metreleptin, a recombinant analog of the human hormone leptin, is an orphan drug used to treat complications of leptin deficiency in people with congenital or acquired lipodystrophy. Affecting less than 500 people worldwide, lipodystrophy is characterized by a lack of adipose tissue, fat deposition in the muscles and liver, and metabolic complications such as hypertriglyceridemia, insulin resistance, diabetes mellitus, and fatty liver disease. These metabolic abnormalities are often aggravated by excessive food intake, which is further aggravated by leptin deficiency, a protein secreted by adipose tissue. Administration of Metreleptin results in improvement of metabolic symptoms including improvements in insulin resistance, reduced HbA1c and fasting glucose, reduced triglycerides, and reductions in food intake. Metreleptin is produced in E. coli and differs from native human leptin by the addition of a methionine residue at its amino terminus. It is administered as a once daily subcutaneous injection. On Feb. 24, 2014, Metreleptin was approved by the FDA for the treatment of complications of leptin deficiency, in addition to diet, in patients with congenital generalized or acquired generalized lipodystrophy. Metreleptin is marketed under the brand Myalept® by Aegerion Pharmaceuticals, Inc. |
| PubChem ID: | -- |
| CasNo: | 186018-45-1 |
| Repositioning for NAFLD: | Yes |
| SMILES: | -- |
| InChiKey: | -- |
| Molecular Weight: | -- |
| DrugBank Targets: | Leptin receptor agonist |
| DrugBank MoA: | Metreleptin functions by binding to and activating the human leptin receptor (ObR), which belongs to the Class I cytokine family of receptors that signals through the JAK/STAT transduction pathway. |
| DrugBank Pharmacology: | In patients with leptin deficiency, clinical trials demonstrated that exogenous leptin administration results in weight loss, reduction in mean HbA1c and fasting glucose levels, reduced blood insulin, and reduced triglyceride levels leading to improved insulin sensitivity and reductions in food intake. |
| DrugBank Indication: | Metreleptin is indicated as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy. |
| Targets: | LEPR agonist |
| Therapeutic Category: | CNS drug |
| Clinical Trial Progress: | Phase 2 completed (NCT02654977) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0108 | NCT01679197 | Phase 2 | Completed | Has Results | October 8, 2012 | June 14, 2017 | Details |
| L0191 | NCT00596934 | Phase 2 | Completed | Has Results | February 2006 | November 24, 2017 | Details |
| L0355 | NCT02654977 | Phase 2 | Completed | Has Results | September 29, 2015 | November 24, 2020 | Details |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A07231 | 32573497 | JCI Insight | Leptin decreases de novo lipogenesis in patients with lipodystrophy. | Details |
| A12253 | 30545408 | J Med Case Rep | Acquired partial lipoatrophy as graft-versus-host disease and treatment with metreleptin: two case reports. | Details |
| A13010 | 30182761 | Endocr Res | A subset of patients with acquired partial lipodystrophy developing severe metabolic abnormalities. | Details |
| A16543 | 28324110 | J Clin Endocrinol Metab | Effects of Metreleptin in Pediatric Patients With Lipodystrophy. | Details |
| A20251 | 26063386 | Expert Opin Biol Ther | Metreleptin and generalized lipodystrophy and evolving therapeutic perspectives. | Details |
| A42263 | 35046902 | Front Endocrinol (Lausanne) | Molecular and Cellular Bases of Lipodystrophy Syndromes. | Details |
| A45328 | 25156686 | Metabolism | Leptin treatment: facts and expectations. | Details |
| A47770 | 32213649 | Endocrinol Diabetes Metab Case Rep | The complicated clinical course in a case of atypical lipodystrophy after development of neutralizing antibody to metreleptin: treatment with setmelanotide. | Details |
| A48783 | 28895299 | J Diabetes Investig | Case of lipoatrophic diabetes induced by juvenile dermatomyositis. | Details |
| A49210 | 35821558 | Curr Diab Rep | Lipodystrophy for the Diabetologist-What to Look For. | Details |
| A50710 | 35291351 | Med (N Y) | Metreleptin therapy for nonalcoholic steatohepatitis: Open-label therapy interventions in two different clinical settings. | Details |
| A51162 | 35417107 | J Pediatr Endocrinol Metab | Successful treatment of severe hypertriglyceridemia with icosapent ethyl in a case of congenital generalized lipodystrophy type 4. | Details |
| A52075 | 31656583 | F1000Res | Recent advances in understanding lipodystrophy: a focus on lipodystrophy-associated cardiovascular disease and potential effects of leptin therapy on cardiovascular function. | Details |
| A52190 | 30296183 | Curr Med Res Opin | Monogenic forms of lipodystrophic syndromes: diagnosis, detection, and practical management considerations from clinical cases. | Details |