Trial reportThe Journal of clinical investigation2018
Metreleptin-mediated improvements in insulin sensitivity are independent of food intake in humans with lipodystrophy.
Trial report in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 96 citations in OpenAlex.
- Effect of exercise on hormonal responses in adolescents with obesity and leptin resistance: a randomized trial.Scientific reports · 2026Trial
- Efficacy and Safety of Obeticholic Acid for Treating Hepatic Steatosis in Patients With Familial Partial Lipodystrophy.The Journal of clinical endocrinology and metabolism · 2025Trial
- Leptin Decreases Energy Expenditure Despite Increased Thyroid Hormone in Patients With Lipodystrophy.The Journal of clinical endocrinology and metabolism · 2021Trial
- Clamping Cortisol and Testosterone Mitigates the Development of Insulin Resistance during Sleep Restriction in Men.The Journal of clinical endocrinology and metabolism · 2021Trial
- Metabolic impact of weight loss induced reduction of adipose ACE-2 - Potential implication in COVID-19 infections?Metabolism: clinical and experimental · 2020Trial
- Free fatty acid processing diverges in human pathologic insulin resistance conditions.The Journal of clinical investigation · 2020Trial
- Thyroid Hormone Effects on Glucose Disposal in Patients With Insulin Receptor Mutations.The Journal of clinical endocrinology and metabolism · 2020Trial
- Volanesorsen, an antisense oligonucleotide to apolipoprotein C-III, increases lipoprotein lipase activity and lowers triglycerides in partial lipodystrophy.Journal of clinical lipidologyTrial
- Cardiometabolic regulation by adipocyte-derived leptin and the brain melanocortin system.Clinical science (London, England : 1979) · 2026Review
- Liraglutide use in congenital generalized lipodystrophy: glycemic and metabolic outcomes.Frontiers in endocrinology · 2026Article
- Novel and Ultrarare Heterozygous Missense LMNA Variants Causing Familial Partial Lipodystrophy.The Journal of clinical endocrinology and metabolism · 2025Article
- Central leptin pathways in metabolic homeostasis.Clinical science (London, England : 1979) · 2025Review
- Clinical Guidance for Lipodystrophy Syndromes: From Diagnosis and Work-Up to Treatment.Current diabetes reports · 2025Review
- Changes After Leptin Administration in Partial Lipodystrophy and Factors Associated With Hepatic and Metabolic Response.Journal of the Endocrine Society · 2025Article
- Oral Glucagon-Like Peptide 1 Analog as an Adjuvant Therapy in Generalized Lipodystrophy.Diabetes care · 2025Article
- Metabolic Improvements With Tirzepatide in Lipodystrophy: A Novel Option?Diabetes care · 2025Observational
- Adipose Tissue Plasticity: A Comprehensive Definition and Multidimensional Insight.Biomolecules · 2024Review
- The blockade of the TGF-β pathway alleviates abnormal glucose and lipid metabolism of lipodystrophy not obesity.Pharmacology research & perspectives · 2024Article
- Leptin Decreases Gluconeogenesis and Gluconeogenic Substrate Availability in Patients With Lipodystrophy.The Journal of clinical endocrinology and metabolism · 2023Article
- Across-species benefits of adrenalectomy on congenital generalized lipoatrophic diabetes: a review.Frontiers in endocrinology · 2023Review
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundRecombinant leptin (metreleptin) ameliorates hyperphagia and metabolic abnormalities in leptin-deficient humans with lipodystrophy. We aimed to determine whether metreleptin improves glucose and lipid metabolism in humans when food intake is held constant.
methodsPatients with lipodystrophy were hospitalized for 19 days, with food intake held constant by a controlled diet in an inpatient metabolic ward. In a nonrandomized, crossover design, patients previously treated with metreleptin (n = 8) were continued on metreleptin for 5 days and then taken off metreleptin for the next 14 days (withdrawal cohort). This order was reversed in metreleptin-naive patients (n = 14), who were reevaluated after 6 months of metreleptin treatment on an ad libitum diet (initiation cohort). Outcome measurements included insulin sensitivity by hyperinsulinemic-euglycemic clamp, fasting glucose and triglyceride levels, lipolysis measured using isotopic tracers, and liver fat by magnetic resonance spectroscopy.
resultsWith food intake constant, peripheral insulin sensitivity decreased by 41% after stopping metreleptin for 14 days (withdrawal cohort) and increased by 32% after treatment with metreleptin for 14 days (initiation cohort). In the initiation cohort only, metreleptin decreased fasting glucose by 11% and triglycerides by 41% and increased hepatic insulin sensitivity. Liver fat decreased from 21.8% to 18.7%. In the initiation cohort, changes in lipolysis were not independent of food intake, but after 6 months of metreleptin treatment on an ad libitum diet, lipolysis decreased by 30% (palmitate turnover) to 35% (glycerol turnover).
conclusionUsing lipodystrophy as a human model of leptin deficiency and replacement, we show that metreleptin improves insulin sensitivity and decreases hepatic and circulating triglycerides and that these improvements are independent of its effects on food intake.
trial registrationClinicalTrials.gov NCT01778556FUNDING. This research was supported by the intramural research program of the NIDDK.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.