Metreleptin in lipodystrophy: a profile of its use

Deeks, Emma D.

doi:10.1007/s40267-019-00622-y

Cited by 5 publications

(3 citation statements)

References 31 publications

(65 reference statements)

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“…Lipodystrophy syndromes are rare and heterogeneous leptin deficiency and body fat disorders, associated with increased mortality and a range of comorbidities [1][2][3][4] . The general or partial lack of normal fat deposits can result in metabolic symptoms, specifically insulin resistance, diabetes mellitus, and hypertriglyceridemia 1,5 .…”

Section: Introductionmentioning

confidence: 99%

Effects of metreleptin in patients with lipodystrophy with and without baseline concomitant medication use

Adamski

Cook

Gupta

et al. 2021

Current Medical Research and Opinion

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Objective: To evaluate the effects of metreleptin in distinct subgroups of patients with generalized lipodystrophy (GL) and partial lipodystrophy (PL), using multivariate linear regression modeling to account for the role of patients' baseline usage of concomitant glucose and lipid-lowering medications and other covariates on their outcomes. Materials and methods: A post-hoc statistical analysis of two published single-arm, interventional, phase 2 clinical trials at NIH was conducted. Concomitant medication use was assessed for the clinical trial population using prescription fill data, measured at baseline and the post-one year following metreleptin initiation. Pre-specified co-primary efficacy endpoints measured were change from baseline in HbA1c at month 12, and the percent change from baseline in fasting serum triglycerides (TG) at month 12. Descriptive and statistical analyses were conducted for the overall population, the separate populations with GL and PL, and additional PL subgroups defined by baseline metabolic markers of elevated HbA1c and elevated fasting TG. Results: As previously reported, improvement in HbA1c and fasting TG from baseline to 12 months on metreleptin were observed in the overall population (mean change À1.57 percentage points and median change À37.9%, respectively) and subgroups. For both HbA1c and TG, baseline levels were significant predictors of changes after metreleptin. After considering baseline characteristics such as disease type, age, sex, and baseline HbA1c, baseline insulin use was not found to be a significant predictor of HbA1c improvement following metreleptin initiation. Similar results were seen for TG levels, with the use of any lipid-lowering medications at baseline not found to be a significant predictor of reductions in fasting TG levels. Conclusions: Patients treated with metreleptin experienced statistically significant improvement in metabolic markers of glycemic and hypertriglyceridemic control-e.g. HbA1c and triglyceride levelsacross various subgroups after controlling for baseline characteristics and concomitant medication usage.

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Section: Introductionmentioning

confidence: 99%

Effects of metreleptin in patients with lipodystrophy with and without baseline concomitant medication use

Adamski

Cook

Gupta

et al. 2021

Current Medical Research and Opinion

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show abstract

“…However, antimetreleptin antibodies have been identified in 36 out of 43 patients examined in a study. In addition, 2 patients had neutralizing antibodies, condition connected to infections, and metabolic imbalance [117]. The possibility that the neutralizing antibody may attenuate the effect of endogenous leptin along with metreleptin has to be considered.…”

Section: Treatmentmentioning

confidence: 99%

Lipodystrophies in Children

Mainieri¹,

Chiarelli²

2022

Horm Res Paediatr

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Background: Lipodystrophy includes a wide group of diseases characterized by reduction, absence or altered distribution of adipose tissue. Lipodystrophies are classified into generalized or partial, according to the fat distribution, and congenital or acquired, considering the aetiology. Summary: Impaired glucose and lipid metabolism is typically present, thus severe insulin resistance, diabetes mellitus, dyslipidemia and hepatic steatosis are frequent complications. Because of the rarity and the diversification of lipodystrophies, diagnosis might be challenging, typically for partial forms that cannot be easily recognized, leading to progression of the several metabolic abnormalities associated. First management of lipodystrophy is diet and lifestyle changes, followed by the treatment of metabolic complications. Replacement therapy with metreleptin, currently available in the United States and Europe, has shown improvement of metabolic profile in a great number of patients with lipodystrophy. Key messages: The purpose of this review is to describe the phenotypic characteristics of all the known lypodistrophic types and to present specific steps for obtaining early diagnosis and assessing the best treatment of lipodystrophy.

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“…The therapeutic approach includes at first diet and exercise, as in the obesity, and then the specific treatment for each metabolic complication that appears; injectable fillers, plastic, and bariatric surgery are often valid alternatives. Recently, the use of a recombinant leptin, metreleptin, has been accepted as a therapy to treat metabolic complications in the context of leptin deficiency [99].…”

Section: Ir In Leanness and Syndromes Associated With Irmentioning

confidence: 99%

Early Insulin Resistance, Type 2 Diabetes, and Treatment Options in Childhood

Polidori¹,

Mainieri²,

Chiarelli³

et al. 2021

Horm Res Paediatr

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Background T2D (Type 2 Diabetes) represents just the tip of the iceberg of the complex metabolic alterations associated with obesity and other clinical conditions associated to impaired adipose tissue storage. Summary Available data have suggested the presence of a continuous spectrum of metabolic alterations developed in the progression from IR to T2D, most of which are likely preventable through the early characterization of all the multiple risk factors involved. Therefore, the complete characterization of the natural history of the disease and the major modifiable factors represents a milestone in the daily care of young subject at risk for the development of impaired glucose metabolism early in life. This review will focus on the main components defining the risk of IR and T2D in childhood with a specific focus on the main aspects of treatment options available in children and adolescents. Key messages Impaired adipose tissue storage documented in obesity results in a continuous spectrum of metabolic alterations ranging from IR to T2DM. These metabolic alterations are mostly likely preventable through the early characterization of all the multiple risk factors involved. The complete characterization of the disease and of the major modifiable factors represent a milestone in the daily care of young subject at risk for the development of impaired glucose metabolism early in life.

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Metreleptin in lipodystrophy: a profile of its use

Cited by 5 publications

References 31 publications

Effects of metreleptin in patients with lipodystrophy with and without baseline concomitant medication use

Effects of metreleptin in patients with lipodystrophy with and without baseline concomitant medication use

Lipodystrophies in Children

Early Insulin Resistance, Type 2 Diabetes, and Treatment Options in Childhood

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