AUSTIN, Texas — Patients with generalized lipodystrophy, a rare syndrome characterized by abnormal fat distribution and often associated with insulin resistance, dyslipidemia and fatty liver disease, experienced significant improvement in these conditions with leptin therapy, researchers reported at the American Association of Clinical Endocrinologists Annual Scientific and Clinical Congress.
“Hepatomegaly is a common problem in patients with generalized lipodystrophy. The liver volumes are quite remarkably elevated, and leptin therapy can help treat this physical abnormality,” Elif Oral, MD, associate professor of medicine at the University of Michigan, told Endocrine Today. “Leptin’s ability to address this clinical finding is quite unique, and patients find this improvement significant for their mobility and pain as well.”
Oral and colleagues conducted a post hoc analysis of a prospective, open-label study that assessed the effects of the leptin analogue metreleptin (Myalept, Aegerion Pharmaceuticals) on hepatomegaly. The study included 21 patients with generalized lipodystrophy (mean age, 17 years; 13 patients aged younger than 20 years). Most patients were women (n = 14). Liver disease (n = 18), diabetes (n = 19) and hypertriglyceridemia (n = 16) were common in this population. Participants were assigned metreleptin dosage based on weight and individual clinical response. The study was conducted at NIH from Aug. 3, 2000, through Dec. 31, 2008.
At baseline, all participants had liver volumes, assessed by MRI, from one to six times
normal, and measuring at least 2,000 mL in all but one patient. After a mean 9.8 months of treatment, liver volume had decreased by –24.5% (95% CI, –32.1% to –17.0%), aspartate aminotransferase by –41.7% (95% CI, –60.8 to –22.7), alanine aminotransferase by –46.1% (95% CI, –65.3 to –26.9), HbA1c by –2.1% (95% CI, –2.7 to –1.5) and fasting triglycerides by –43.7% (95% CI, –64.0 to –23.3). Decrease in liver volume occurred soon after treatment initiation in most patients and was sustained in those continuing treatment beyond 12 months, according to the researchers.
Abdominal pain and hypoglycemia were the most common adverse events, and were experienced by six participants.
“Leptin reduces liver volume quite dramatically in patients with generalized lipodystrophy in a sustained manner,” Oral said. “We have other studies ... that suggest that the improvement in the liver volume is due to improvement in steatosis.”
The researchers plan to present more on those studies at the American Diabetes Scientific Sessions in June. – by Jill Rollet
Oral E, et al. Abstract #727. Presented at: AACE Annual Scientific and Clinical Congress; May 3-7, 2017; Austin, Texas.
: Oral reports serving as a consultant/advisor to and receiving grant/drug support from Aegerion Pharmaceuticals, Akcea Therapeutics, Amylin, AstraZeneca, Bristol-Myers Squibb and Ionis Pharmaceuticals. Please see the abstract for other authors’ relevant financial disclosures.