Trial reportDiabetes2011
Efficacy of metreleptin in obese patients with type 2 diabetes: cellular and molecular pathways underlying leptin tolerance.
Trial report in Diabetes, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
80 citing papers in PubMed, 1 synthesis or guideline pooled it, 150 citations in OpenAlex.
- Pediatric Obesity-Assessment, Treatment, and Prevention: An Endocrine Society Clinical Practice Guideline.The Journal of clinical endocrinology and metabolism · 2017 · on this mapGuideline
- Metreleptin therapy for nonalcoholic steatohepatitis: Open-label therapy interventions in two different clinical settings.Med (New York, N.Y.) · 2021Trial
- Associations of leptin and adiponectin with incident type 2 diabetes and interactions among African Americans: the Jackson heart study.BMC endocrine disorders · 2020Trial
- Partial and generalized lipodystrophy: comparison of baseline characteristics and response to metreleptin.The Journal of clinical endocrinology and metabolism · 2015Trial
- Trial
- Randomized double-blind placebo-controlled study of leptin administration after gastric bypass.Obesity (Silver Spring, Md.) · 2013Trial
- Leptin administration to overweight and obese subjects for 6 months increases free leptin concentrations but does not alter circulating hormones of the thyroid and IGF axes during weight loss induced by a mild hypocaloric diet.European journal of endocrinology · 2011Trial
- Leptin treatment reduces body fat but does not affect lean body mass or the myostatin-follistatin-activin axis in lean hypoleptinemic women.American journal of physiology. Endocrinology and metabolism · 2011Trial
- Research Progress on Leptin in Metabolic Dysfunction-associated Fatty Liver Disease.Journal of clinical and translational hepatology · 2025Review
- Antiobesity Pharmacotherapy for Patients With Genetic Obesity Due to Defects in the Leptin-Melanocortin Pathway.Endocrine reviews · 2025Review
- Decoding the Multiple Identities and Crosstalk of Organokines in Obesity-Related Type 2 Diabetes Mellitus.Aging and disease · 2025Review
- Impact of Resistance and Endurance Training on Ghrelin and Plasma Leptin Levels in Overweight and Obese Subjects.International journal of molecular sciences · 2024Review
- A negative feedback loop between TET2 and leptin in adipocyte regulates body weight.Nature communications · 2024Article
- Neurological and metabolic related pathophysiologies and treatment of comorbid diabetes with depression.CNS neuroscience & therapeutics · 2024Review
- Review
- Cellular and Molecular Activities of IP6 in Disease Prevention and Therapy.Biomolecules · 2023Review
- Pathophysiology of obesity and its associated diseases.Acta pharmaceutica Sinica. B · 2023Review
- Adipokines as Clinically Relevant Therapeutic Targets in Obesity.Biomedicines · 2023Review
- Effects of Angiotensin Receptor-Neprilysin Inhibitors (ARNIs) on the Glucose and Fat Metabolism Biomarkers Leptin and Fructosamine.Journal of clinical medicine · 2023Article
- Pharmacotherapy of obesity: an update on the available medications and drugs under investigation.EClinicalMedicine · 2023Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
objectiveMetreleptin has been efficacious in improving metabolic control in patients with lipodystrophy, but its efficacy has not been tested in obese patients with type 2 diabetes. RESEARCH DESIGN AND
methodsWe studied the role of leptin in regulating the endocrine adaptation to long-term caloric deprivation and weight loss in obese diabetic subjects over 16 weeks in the context of a double-blinded, placebo-controlled, randomized trial. We then performed detailed interventional and mechanistic signaling studies in humans in vivo, ex vivo, and in vitro.
resultsIn obese patients with diabetes, metreleptin administration for 16 weeks did not alter body weight or circulating inflammatory markers but reduced HbA(1c) marginally (8.01 ± 0.93-7.96 ± 1.12, P = 0.03). Total leptin, leptin-binding protein, and antileptin antibody levels increased, limiting free leptin availability and resulting in circulating free leptin levels of ∼50 ng/mL. Consistent with clinical observations, all metreleptin signaling pathways studied in human adipose tissue and peripheral blood mononuclear cells were saturable at ∼50 ng/mL, with no major differences in timing or magnitude of leptin-activated STAT3 phosphorylation in tissues from male versus female or obese versus lean humans in vivo, ex vivo, or in vitro. We also observed for the first time that endoplasmic reticulum (ER) stress in human primary adipocytes inhibits leptin signaling.
conclusionsIn obese patients with diabetes, metreleptin administration did not alter body weight or circulating inflammatory markers but reduced HbA(1c) marginally. ER stress and the saturable nature of leptin signaling pathways play a key role in the development of leptin tolerance in obese patients with diabetes.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.