Metreleptin

In the European Union, metreleptin is indicated in addition to diet to treat lipodystrophy, where people have a loss of fatty tissue under the skin and a build-up of fat elsewhere in the body such as in the liver and muscles. It is used in adults and children above the age of two years with generalised lipodystrophy (Berardinelli-Seip syndrome and Lawrence syndrome); and in adults and children above the age of twelve years with partial lipodystrophy (including Barraquer-Simons syndrome), when standard treatments have failed.{{cite web | title=Myalepta EPAR | website=European Medicines Agency (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/myalepta | access-date=6 October 2020}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

In the United States, it is indicated as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency in people with congenital or acquired generalized lipodystrophy.{{cite web | title=Myalept- metreleptin injection, powder, lyophilized, for solution | work = DailyMed | publisher = U.S. National Library of Medicine | date=26 May 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c986f93b-855d-4ef0-b620-5d41a0513e48 | access-date=6 October 2020}}

Metreleptin is being investigated for the treatment of diabetes and/or hypertriglyceridemia, in patients with rare forms of lipodystrophy, syndromes characterized by abnormalities in adipose tissue distribution, and severe metabolic abnormalities.{{cite web | url = http://www.diabetesincontrol.com/articles/53-/12611-amylin-seeks-fda-approval-for-metreleptin | title = Amylin Seeks FDA Approval for Metreleptin | date = 11 April 2012 | publisher = diabetesincontrol.com | access-date = 26 February 2014 | archive-date = 8 April 2014 | archive-url = https://web.archive.org/web/20140408050958/http://www.diabetesincontrol.com/articles/53-/12611-amylin-seeks-fda-approval-for-metreleptin | url-status = dead }} The FDA approved Metreleptin injection for treating complications of leptin deficiency in February 2014.{{medcn|date=May 2020}}

In a three-year study of metreleptin in patients with lipodystrophy organized by the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health, metreleptin treatment was associated with a significant decrease in blood glucose (A1c decreased from 9.4% at baseline to 7.0% at study end) and triglyceride concentration (from 500 mg/dl at baseline to 200 mg/dl at study end).{{cite web | url = http://investors.amylin.com/phoenix.zhtml?c=101911&p=irol-newsArticle&ID=1550945&highlight | title = Amylin to Present Data Showing Investigational Metreleptin Treatment Led to Long-Term Improvements in Diabetes and Lipid Control in Patients with Lipodystrophy | date = 15 April 2011 | work = Press Release | publisher = Amylin Pharmaceuticals | access-date = 27 October 2011 }}{{dead link|date=January 2018 |bot=InternetArchiveBot |fix-attempted=yes }} Metreleptin is effective in most patients with generalized lipodystrophy where circulating leptin levels are extremely low. Analogous to insulin replacement for patients with type 1 Diabetes, metreleptin restores the function of a deficient hormone. However, in patients with partial lipodystrophy where there is only a relative leptin deficiency, the response to metreleptin is not universal.{{cite journal | vauthors = Meral R, Malandrino N, Walter M, Neidert AH, Muniyappa R, Oral EA, Brown RJ | title = Endogenous Leptin Concentrations Poorly Predict Metreleptin Response in Patients With Partial Lipodystrophy | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 107 | issue = 4 | pages = e1739–e1751 | date = March 2022 | pmid = 34677608 | pmc = 8947785 | doi = 10.1210/clinem/dgab760 }} This may or may not be due to anti-leptin antibodies.

Metreleptin is undergoing research for its potential benefit in the treatment of anorexia nervosa.{{cite journal | vauthors = Hebebrand J, Hildebrandt T, Schlögl H, Seitz J, Denecke S, Vieira D, Gradl-Dietsch G, Peters T, Antel J, Lau D, Fulton S | title = The role of hypoleptinemia in the psychological and behavioral adaptation to starvation: Implications for anorexia nervosa | journal = Neuroscience and Biobehavioral Reviews | volume = 141 | pages = 104807 | date = October 2022 | pmid = 35931221 | doi = 10.1016/j.neubiorev.2022.104807 | s2cid = 251259742 }} It is hypothesized that the gradual loss of body fat mass, and more specifically the ensuing low leptin levels, escalate the preexisting drive for thinness into an obsessive-compulsive-like and addictive-like state. It was shown that short-term metreleptin treatment of patients with anorexia nervosa had rapid on-set of beneficial cognitive, emotional, and behavioral effects.{{cite journal | vauthors = Milos G, Antel J, Kaufmann LK, Barth N, Koller A, Tan S, Wiesing U, Hinney A, Libuda L, Wabitsch M, von Känel R, Hebebrand J | title = Short-term metreleptin treatment of patients with anorexia nervosa: rapid on-set of beneficial cognitive, emotional, and behavioral effects | journal = Translational Psychiatry | volume = 10 | issue = 1 | pages = 303 | date = August 2020 | pmid = 32855384 | pmc = 7453199 | doi = 10.1038/s41398-020-00977-1 }} Among other things, depression, drive for activity, repetitive thoughts of food, inner restlessness, and weight phobia decreased rapidly. Whether metreleptin (or another leptin analogue) is a suitable treatment for anorexia nervosa remains to be seen. Potential side effects are weight loss and the development of anti-metreleptin antibodies.

In a clinical study, metreleptin treatment improved non-alcoholic steatohepatitis (fatty liver disease) both in patients with partial lipodystrophy and in those with relative leptin deficiency. Both steatosis and hepatic injury scores decreased.{{cite journal | vauthors = Akinci B, Subauste A, Ajluni N, Esfandiari NH, Meral R, Neidert AH, Eraslan A, Hench R, Rus D, McKenna B, Hussain HK, Chenevert TL, Tayeh MK, Rupani AR, Innis JW, Mantzoros CS, Conjeevaram HS, Burant CL, Oral EA | title = Metreleptin therapy for nonalcoholic steatohepatitis: Open-label therapy interventions in two different clinical settings | journal = Med | volume = 2 | issue = 7 | pages = 814–835 | date = July 2021 | pmid = 35291351 | pmc = 8920072 | doi = 10.1016/j.medj.2021.04.001 }} Metreleptin reduces body weight in overweight people with low leptin levels.{{cite journal | vauthors = Depaoli A, Long A, Fine GM, Stewart M, O'Rahilly ST |title=Efficacy of Metreleptin for Weight Loss in Overweight and Obese Adults with Low Leptin Levels |journal=Diabetes |date=1 July 2018 |volume=67 |issue=Supplement_1 |doi=10.2337/db18-296-LB |s2cid=90583209 |url=https://diabetesjournals.org/diabetes/article/67/Supplement_1/296-LB/57133/Efficacy-of-Metreleptin-for-Weight-Loss-in|url-access=subscription }}

Although it is not very effective as a weight loss drug, leptin levels are lowered in people who have lost weight and it is hypothesized that supplemental leptin could help them with weight loss maintenance. However, there is no regulatory pathway for drug approval for this indication.{{cite journal | vauthors = Christoffersen BØ, Sanchez-Delgado G, John LM, Ryan DH, Raun K, Ravussin E | title = Beyond appetite regulation: Targeting energy expenditure, fat oxidation, and lean mass preservation for sustainable weight loss | journal = Obesity | volume = 30 | issue = 4 | pages = 841–857 | date = April 2022 | pmid = 35333444 | doi = 10.1002/oby.23374 | pmc = 9310705 }}

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Category:Leptin receptor agonists

Category:Systemic hormonal preparations

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