“Metreleptin Treatment Leads to Long-Term Improvements in Diabetes and Lipid Control in Patients with Lipodystrophy”

RESULTS from a new analysis of an ongoing, long-term research study of the investigational drug metreleptin, an analog of the human hormone leptin, demonstrated robust reductions in HbA1c levels and triglycerides that were sustained for several years of treatment in patients with lipodystrophy.


“Lipodystrophy is a rare, debilitating chronic disease with a large, unmet clinical need. No therapies are indicated specifically for the treatment of the metabolic abnormalities associated with lipodystrophy,” Christian Weyer, MD, senior vice president, research and development, Amylin Pharmaceuticals, said at a late-breaking oral session on April 17 at the 20th Annual Meeting and Clinical Congress of the American Association of Clinical Endocrinologists (AACE) in San Diego.

In the study, which has been ongoing for more than 10 years, researchers at the NIH are examining the effects of metreleptin on several metabolic abnormalities, such as diabetes and hypertriglyceridemia, in patients with rare inherited or acquired forms of lipodystrophy.

[Amylin recently submitted the clinical and nonclinical sections of a rolling Biologics License Application (BLA) for metreleptin to treat diabetes and/or hypertriglyceridemia (high levels of triglycerides in the bloodstream) in patients with rare inherited or acquired forms of lipodystrophy. If approved, metreleptin would be the first therapy indicated specifically for the treatment of diabetes and high triglycerides in patients with lipodystrophy, and the first approved therapeutic use of leptin.]

Weyer presented results of an analysis of 55 patients with lipodystrophy who were assigned to metreleptin. According to the researchers, this is the largest cohort to date. At baseline, 75% of patients had uncontrolled diabetes (HbA1c ≥7%) and 75% had hypertriglyceridemia (≥200 mg/dl).

“When metreleptin was introduced as a subcutaneous injection once or twice a day, both HbA1c and triglycerides fell very rapidly and profoundly in the first 4 months of therapy,” Weyer said. When patients were followed to 3 years, the changes were maintained. In the patients with diabetes, mean HbA1c decreased from 9.4% at baseline to lower than 7% at year 3. In the patients with hypertriglyceridemia, mean triglyceride concentrations decreased from 500 mg/dl to under 200 mg/dl at year 3.

Weyer said adverse events were consistent with known comorbid conditions of lipodystrophy, including pancreatitis, proteinuria and autoimmune/chronic hepatitis, or expected pharmacological effects of metreleptin, such as weight loss or insulin-induced hypoglycemia in the setting of improved insulin sensitivity in patients taking high doses of insulin.

Other studies conducted worldwide have demonstrated metreleptin’s positive effects on insulin sensitivity, high triglycerides, hyperglycemia and liver fat in patients with lipodystrophy who are not responsive to conventional lipid and glucose-lowering agents, the researchers said. Amylin is working with the FDA to get approval of metreleptin. If approved, it would be the first therapy indicated specifically for the treatment of diabetes and hypertriglyceridemia in patients with lipodystrophy.

Commenting on Weyer’s remarks, AACE President Elect Yehuda Handelsman, MD, said:

This whole thing about leptin is fascinating, and I think there is so much more to learn about it. (News about) leptin is everywhere: it is related to bone, it turns out, it is related to smell, taste and hunger. We found out from Dr. Unger (here at the meeting) that it suppresses glucagon terrifically.

Dr. Weyer represents an organization that has a drug called exenatide (Byetta), a glucagon-like peptide 1 that we also think in some way suppresses glucagon. It will be interesting to know if there is any relationship between the leptin suppression and glucagon suppression. We can see now that leptin, in the rarest disease, may be more applicable to a larger group of people that may have partial lipodystrophy, and we don’t as yet know how to recognize it.

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