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Metreleptin improves cardiometabolic profile in children with lipodystrophy
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Children with lipodystrophy and a related cardiometabolic condition saw improvements in glycemic control and lipid profile after 1 year of metreleptin therapy, according to recent findings.
Rebecca J. Brown, MD, MHSc, of the National Institute of Diabetes and Digestive and Kidney Diseases at the NIH, and colleagues analyzed data from 53 children with lipodystrophy and a metabolic abnormality (diabetes, insulin resistance or hypertriglyceridemia) enrolled in open-label studies of metreleptin (Myalept, Aegerion) at the NIH (mean age, 13 years; 41 girls; 72% with diabetes; mean endogenous leptin, 1.1 ng/mL). Patients received subcutaneous metreleptin injections between 0.04 mg/kg and 0.19 mg/kg once or twice daily for a mean treatment duration of 12 months. Primary outcome was change in HbA1c, lipid profile and transaminases at 12 and 61 months, as well as changes in liver histology, growth and pubertal development throughout treatment.
At 12 months, HbA1c decreased from a mean of 8.3% to 6.5% (P < .0001), whereas mean fasting glucose fell from 176 mg/dL to 121 mg/dL (P < .0001). At 1 year, the percentage of patients requiring insulin fell from 45% to 23%; among those using insulin, the dose decreased from a mean of 385 U per day to 138 U per day (P = .008). The number of diabetes medications fell from a mean of 1 to 0.8 (P = .03).
Lipid outcomes also improved after metreleptin therapy. LDL cholesterol decreased from a mean of 96 mg/dL to 75 mg/dL (P = .0005); triglycerides fell from a mean of 374 mg/dL to 189 mg/dL (P < .0001); alanine transaminase decreased from a mean of 73 U/L to 41 U/L; aspartate transaminase fell from 51 U/L to 26 U/L. Researchers observed sustained improvements among patients with long-term follow-up (n = 47; mean age, 18 years; mean duration, 61 months).
Among the 17 patients who underwent liver biopsies before and after completion of metreleptin therapy, 15 met criteria for nonalcoholic steatohepatitis (NASH) before therapy; 10 met NASH criteria after completion of therapy.
NAFLD activity score decreased from 4.5 to 3.4 after 3.3 years of metreleptin (P = 0.03).
Researchers did not observe clinically significant changes in growth or puberty.
“Adolescents had greater severity of metabolic disease prior to metreleptin, supporting the
idea that, in the absence of leptin replacement, complications of lipodystrophy tend to worsen with age,” the researchers wrote. “Because of the milder metabolic derangements in children, and smaller sample size, most improvements with metreleptin observed in adolescents were not significant in children. However, metreleptin may be protecting children from progression of metabolic disease, particularly as they enter puberty, when insulin resistance worsens.”
The researchers noted that longer follow-up is needed to determine the impact of metreleptin on life expectancy. – by Regina Schaffer
Disclosure: The researchers report no relevant financial disclosures.
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