Metreleptin, sold under the brand name Myalept among others, is a synthetic
analog of the hormone
leptin
Leptin (from Ancient Greek, Greek λεπτός ''leptos'', "thin" or "light" or "small"), also known as obese protein, is a protein hormone predominantly made by adipocytes (cells of adipose tissue). Its primary role is likely to regulate long ...
used to treat various forms of
dyslipidemia
Dyslipidemia is a metabolic disorder characterized by abnormally high or low amounts of any or all lipids (e.g. fats, triglycerides, cholesterol, phospholipids) or lipoproteins in the blood. Dyslipidemia is a risk factor for the development of ...
. It has been approved in Japan for metabolic disorders including
lipodystrophy
Lipodystrophy syndromes are a group of genetic or acquired disorders in which the body is unable to produce and maintain healthy fat tissue. The medical condition is characterized by abnormal or degenerative conditions of the body's adipose tissu ...
and in the United States as replacement therapy to treat the complications of leptin deficiency, in addition to diet, in patients with congenital generalized or acquired generalized lipodystrophy.
The most common side effects include
hypoglycaemia
Hypoglycemia (American English), also spelled hypoglycaemia or hypoglycæmia (British English), sometimes called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's tria ...
(low blood glucose) and weight loss.
It was approved for medical use in Canada in January 2024.
Medical uses
In the European Union, metreleptin is
indicated
In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...
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.
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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.
Research
Metreleptin is being investigated for the treatment of diabetes and/or
hypertriglyceridemia
Hypertriglyceridemia is the presence of high amounts of triglycerides in the blood. Triglycerides are the most abundant fatty molecule in most organisms. Hypertriglyceridemia occurs in various physiologic conditions and in various diseases, and ...
, in patients with rare forms of lipodystrophy, syndromes characterized by abnormalities in adipose tissue distribution, and severe metabolic abnormalities. The FDA approved Metreleptin injection for treating complications of leptin deficiency in February 2014.
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).
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
Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that occurs when the body's immune system destroys pancreatic cells (beta cells). In healthy persons, beta cells produce insulin. Insulin is a hormone require ...
, 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. 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. 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. 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
An alcohol-free or non-alcoholic drink, also known as a temperance drink, is a version of an alcoholic drink made without alcohol, or with the alcohol removed or reduced to almost zero. These may take the form of a non-alcoholic mixed drink or n ...
(fatty liver disease) both in patients with partial lipodystrophy and in those with relative leptin deficiency. Both
steatosis
Steatosis, also called fatty change, is abnormal retention of fat (lipids) within a cell or organ. Steatosis most often affects the liver – the primary organ of lipid metabolism – where the condition is commonly referred to as fatty liver dis ...
and hepatic injury scores decreased. Metreleptin reduces body weight in overweight people with low leptin levels.
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
Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat (adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other conn ...
maintenance. However, there is no regulatory pathway for drug approval for this indication.
References
{{Authority control
Leptin receptor agonists
Systemic hormonal preparations
Drugs developed by AstraZeneca
Orphan drugs
Pharmacology