Barbara Boughton

May 09, 2011

May 9, 2011 (San Diego, California) — An investigational drug that is an analog of leptin has the potential to help patients with lipodystrophy. The leptin analog metreleptin (Amylin Pharmaceuticals) dramatically lowers blood glucose levels and triglycerides, according to researchers here at the American Association of Clinical Endocrinologists (AACE) 20th Annual Meeting and Clinical Congress.

A new analysis of 55 patients in an ongoing 10-year National Institutes of Health study examining the clinical effects of leptin replacement with metreleptin in those with lipodystrophy indicates that the results achieved with the investigational compound are profound and durable, according to presenting researcher Christian Weyer, MD, senior vice president of research and development of Amylin Pharmaceuticals in San Diego. Lipodystrophy affects about 2000 people in the United States, he said.

After a median follow-up of 2.5 years (maximum, 9 years), patients receiving metreleptin had decreased their hemoglobin A1c levels by a mean of 2.6% and reduced their triglyceride levels by a median of 374 mg/dL. Patients with lipodystrophy typically have diabetes that is poorly controlled with currently available medications, including high doses of insulin, and their triglyceride levels can be higher than 10,000 mg/dL, Dr. Weyer noted. "They also have a voracious appetite, and because it's important for them to limit fat intake, this makes treatment very difficult," Dr. Weyer said.

"The treatment response from metreleptin is very robust," said Dr. Weyer in an interview with Medscape Medical News. He noted that patients with lipodystrophy are often misdiagnosed because the disease is not well known in the medical community. "These patients are identified on an infrequent basis because the disorder is so rare, but we're committed to making the drug available to many of them," he said.

However, even once they are diagnosed, patients with lipodystrophy often face an uphill battle. As well as uncontrolled diabetes and triglycerides, the disease puts patients at high risk for acute pancreatitis, accelerated atherosclerosis, diabetic neuropathy, and cirrhosis. Because they often accumulate fat in the skin of the feet, it becomes painful for them to walk. "Patients with lipodystrophy experience a huge disease burden," Dr. Weyer said at a press conference here.

When patients are treated with metreleptin, which is given subcutaneously once or twice a day, their hemoglobin A1c levels and triglycerides fall dramatically in the first 4 months of therapy. The new analysis indicates that these effects are maintained for up to 3 years. In the National Institutes of Health study, 93% of patients had either a hemoglobin A1c level of 7% or higher or a triglyceride level of 200 mg/dL or higher at baseline. At 1 year, the mean reduction in hemoglobin A1c was 1.4%, and the mean reduction in triglycerides was 555 mg/dL.

During the 10 years of the study, patients experienced adverse events that included comorbid conditions associated with lipodystrophy, such as pancreatitis (7.3%), proteinuria (5.5%), and autoimmune hepatitis (5.5%). Insulin-induced hypoglycemia occurred in 14.5% of patients during treatment, and 2 patients experienced injection-site reactions, Dr. Weyer said.

"Leptin is a fascinating hormone, and we have a lot more to learn about it," commented Yehuda Handelsman, MD, president of AACE and medical director of the Metabolic Institute of America. "Most patients with lipodystrophy have an extreme form of insulin resistance. And while lipodystrophy is a rare disease, it may turn out that addressing leptin deficiency may be applicable to a larger group of people. Leptin is involved in everything — including bone metabolism, smell, even hunger," he said. "We're starting to see some very productive research...come out that [studies] leptin," he said.

Amylin has submitted the clinical data from the new analysis to the FDA and plans to complete their application for a biologics license by the end of 2011.

Dr. Weyer is an employee of Amylin Pharmaceuticals. Dr. Handelsman has disclosed no relevant financial relationships.

American Association of Clinical Endocrinologists (AACE) 20th Annual Meeting and Clinical Congress: Late-breaking research presentation 2. Presented April 17, 2011.

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