2 The condition
2.1 Lipodystrophy is a rare, heterogeneous group of syndromes characterised by complete or partial loss, or absence of, subcutaneous adipose tissue. Without sufficient adipose tissue there is disruption of the body's system for regulating energy use and storage. This results in lipid accumulation in abnormal sites such as the liver and muscle. Metabolic abnormalities often occur with lipodystrophy, including: insulin resistance with resultant hyperinsulinemia and diabetes; hepatic steatosis or steatohepatitis; and dyslipidaemia with severe hypertriglyceridaemia. The associated lack of leptin, particularly in people with generalised lipodystrophy, leads to symptoms such as hyperphagia. It may also contribute to the metabolic abnormalities. Hyperphagia, muscle pain and female reproductive dysfunction also have a significant effect on quality of life. Lipodystrophy is often diagnosed late in the disease course or remains undiagnosed.
2.2 Lipodystrophy is generally classified based on the extent or pattern of fat loss (generalised or partial), and whether the disease is congenital or acquired. There are 4 major subtypes: congenital (inherited) and acquired generalised lipodystrophy; and familial (inherited) and acquired partial lipodystrophy.
2.3 The prevalence of lipodystrophy depends on the subtype but is around 2.5 per 1 million of the population overall, with partial lipodystrophy being slightly more common. It is estimated that there are around 200 people with lipodystrophy in England; a proportion of these people will be eligible for metreleptin treatment.
2.4 There are no licensed treatments in the UK for lipodystrophy. The condition is currently managed with lifestyle modifications such as a low-fat diet and exercise; cosmetic surgery; and medication to manage the metabolic disturbances, including lipid-lowering drugs (for example, fibrates and statins) and antidiabetic therapy (for example, metformin, insulin, sulphonylureas, and thiazolidinediones).
2.5 A single National Specialist Service for people with lipodystrophy was established in 2011 at Addenbrooke's Hospital in Cambridge. Treatment with metreleptin is currently provided there as part of an early access programme, under the National Severe Insulin Resistance Service at the hospital.