Leptin replacement therapy for the treatment of non-HAART associated lipodystrophy syndromes: a meta-analysis into the effects of leptin on metabolic and hepatic endpoints

Rodríguez, Alexander J.; Neeman, Teresa; Giles, Aaron G.; Mastronardi, Claudio A.; Filho, Gilberto Paz

doi:10.1590/0004-2730000003174

Cited by 15 publications

(12 citation statements)

References 38 publications

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“…Since lipodystophy clearly indicates changes in adipose storage, the resultant altered adipokine levels may lead to the observed metabolic dysfunction in lipodystrophy. Lipodystrophy is characterized by hypoleptinemia and can be congenital or acquired, such as for HIV-associated lipodystrophy syndrome (HALS) or highly active antiretroviral therapy (HAART) [44,45,46*]. Indeed, lipoatrophy is a state of leptin deficiency [45,46*], and leptin replacement therapy improves insulin resistance and metabolic syndrome in animal models of lipoatrophy [47].…”

Section: Leptin Deficiencymentioning

confidence: 99%

Leptin applications in 2015

Farr

Gavrieli

Mantzoros³

2015

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

189

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Purpose of review To summarize previous and current advancements for leptin therapeutics, we described how leptin may be useful in leptin deficient states such as lipodystrophy, for which leptin was recently approved, and how it may be useful in the future for typical obesity. Recent findings The discovery of leptin in 1994 built the foundation for understanding the pathophysiology and treatment of obesity. Leptin therapy reverses morbid obesity related to congenital leptin deficiency and appears to effectively treat lipodystrophy, a finding which has led to the approval of leptin for the treatment of lipodystrophy in the USA and Japan. Typical obesity, on the other hand, is characterized by hyperleptinemia and leptin resistance. Thus, leptin administration has proven ineffective for inducing weight loss on its own but may be useful in combination with other therapies or for weight loss maintenance. Summary Leptin is not yet able to treat typical obesity, however, it is effective for reversing leptin deficiency-induced obesity and lipodystrophy. New mechanisms and pathways involved in leptin resistance are continuously discovered, while the development of new techniques and drug combinations which may improve leptin’s efficacy and safety regenerate the hope for its use as an effective treatment for typical obesity.

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Section: Leptin Deficiencymentioning

confidence: 99%

Leptin applications in 2015

Farr

Gavrieli

Mantzoros³

2015

Current Opinion in Endocrinology, Diabetes &Amp; Obesity

189

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“…Further studies over the ensuing years continued to validate this initial response [22–24]. A recent meta-analysis showed that metreleptin decreased fasting glucose (standardized mean difference [SMD] 0.75, range 0.36–1.13, P = 0.0001), HbA1c (SMD 0.49, range 0.17–0.81, P = 0.003), triglycerides (SMD 1.00, range 0.69–1.31, P < 0.00001), and liver volume (SMD 1.06, range 0.51–1.61, P = 0.0002) [25]. …”

Section: Leptin Replacement In Lipodystrophymentioning

confidence: 99%

Metreleptin for injection to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy

Meehan

Cochran

Kassai

et al. 2015

Expert Review of Clinical Pharmacology

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The lipodystrophies represent a class of diseases characterized by leptin deficiency. Leptin deficiency is associated with a severe form of the metabolic syndrome characterized by dyslipidemia, insulin resistance, diabetes, and ovarian dysfunction. Metreleptin is the pharmaceutical derived product that has been approved by the Food and Drug Administration (FDA) to treat the severe metabolic abnormalities of the generalized forms of lipodystrophy. Herein we describe the properties of metreleptin, its use in patients, which includes the administration of the drug and how it may be acquired by medical professionals as well as its safety, tolerability, and properties. Finally, we speculate on future uses and development of metreleptin.

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“…Overall, this suggested that metreleptin was more effective in improving the condition of patients with the generalized form of lipodystrophy, even though there is also emerging evidence suggesting that the efficacy of metreleptin could be independent of lipodystrophy etiology. 15 , 16 , 29 Since patients with generalized lipodystrophy suffer more substantial mortality and morbidity due to complications arising from a number of severe metabolic abnormalities, 34 , 35 it is easier to ascertain and/or predict the beneficial outcome of metreleptin therapy in patients with generalized lipodystrophy, as opposed to patients with partial lipodystrophy. Furthermore, as patients with partial lipodystrophy showed a more heterogeneous disease profile, there was an increased variability in the severity of their metabolic abnormalities.…”

Section: Trials Of Metreleptin In Lsmentioning

confidence: 99%

“…In mice and in humans, leptin improves abnormalities of glucose and lipid metabolism, increases insulin sensitivity, reduces the risk of further progression into NAFLD, and restores gonadotropin secretion. 14 , 15 Due to some risks related to the development of neutralizing antibodies and lymphoma, US prescribers must be certified by enrolling in and completing specific training. Although it has been shown that LRT can be safe and effective also in patients with partial forms of lipodystrophy, 15 , 16 its use is currently approved only for cases of generalized non-HIV lipodystrophy.…”

Section: Introductionmentioning

confidence: 99%

New advances in the treatment of generalized lipodystrophy: role of metreleptin

Rodríguez

Mastronardi

Paz-Filho

2015

TCRM

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Recombinant methionyl human leptin or metreleptin is a synthetic leptin analog that has been trialed in patients with leptin-deficient conditions, such as leptin deficiency due to mutations in the leptin gene, hypothalamic amenorrhea, and lipodystrophy syndromes. These syndromes are characterized by partial or complete absence of adipose tissue and hormones derived from adipose tissue, most importantly leptin. Patients deficient in leptin exhibit a number of severe metabolic abnormalities such as hyperglycemia, hypertriglyceridemia, and hepatic steatosis, which can progress to diabetes mellitus, acute pancreatitis, and hepatic cirrhosis, respectively. For the management of these abnormalities, multiple therapies are usually required, and advanced stages may be progressively difficult to treat. Following many successful trials, the US Food and Drug Administration approved metreleptin for the treatment of non-HIV-related forms of generalized lipodystrophy. Leptin replacement therapy with metreleptin has, in many cases, reversed these metabolic complications, with improvements in glucose-insulin-lipid homeostasis, and regression of fatty liver disease. Besides being effective, a daily subcutaneous administration of metreleptin is generally safe, but the causal association between metreleptin and immune complications (such as lymphoma) is still unclear. Moreover, further investigation is needed to elucidate mechanisms by which metreleptin leads to the development of anti-leptin antibodies. Herein, we review clinical aspects of generalized lipodystrophy and the pharmacological profile of metreleptin. Further, we examine studies that assessed the safety and efficacy of metreleptin, and outline some clinical perspectives on the drug.

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Leptin replacement therapy for the treatment of non-HAART associated lipodystrophy syndromes: a meta-analysis into the effects of leptin on metabolic and hepatic endpoints

Cited by 15 publications

References 38 publications

Leptin applications in 2015

Leptin applications in 2015

Metreleptin for injection to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy

New advances in the treatment of generalized lipodystrophy: role of metreleptin

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