The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Enhanced Weight Loss With Pramlintide/Metreleptin: An Integrated Neurohormonal Approach to Obesity Pharmacotherapy
Open accessAbstract
The neurohormonal control of body weight involves a complex interplay between long‐term adiposity signals (e.g., leptin), and short‐term satiation signals (e.g., amylin). In diet‐induced obese (DIO) rodents, amylin/leptin combination treatment led to marked, synergistic, fat‐specific weight loss. To evaluate the weight‐lowering effect of combined amylin/leptin agonism (with pramlintide/metreleptin) in human obesity, a 24‐week, randomized, double‐blind, active‐drug‐controlled, proof‐of‐concept study was conducted in obese or overweight subjects (N = 177; 63% female; 39 ± 8 years; BMI 32.0 ± 2.1 kg/m 2; 93.3 ± 13.2 kg; mean ± s.d.). After a 4‐week lead‐in period with pramlintide (180 µg b.i.d. for 2 weeks, 360 µg b.i.d. thereafter) and diet (40% calorie deficit), subjects achieving 2–8% weight loss were randomized 1:2:2 to 20 weeks of treatment with metreleptin (5 mg b.i.d.), pramlintide (360 µg b.i.d.), or pramlintide/metreleptin (360 µg/5 mg b.i.d.). Combination treatment with pramlintide/metreleptin led to significantly greater weight loss from enrollment to week 20 (−12.7 ± 0.9%; least squares mean ± s.e.) than treatment with pramlintide (−8.4 ± 0.9%; P < 0.001) or metreleptin (−8.2 ± 1.3%; P < 0.01) alone (evaluable, N = 93). The greater reduction in body weight was significant as early as week 4, and weight loss continued throughout the study, without evidence of a plateau. The most common adverse events with pramlintide/metreleptin were injection site events and nausea, which were mostly mild to moderate and decreased over time. These results support further development of pramlintide/metreleptin as a novel, integrated neurohormonal approach to obesity pharmacotherapy.
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Citations
Cites
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ResultGastrointestinal regulation of food intake
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BackgroundLong-Term Efficacy of Leptin Replacement in Patients With Generalized Lipodystrophy
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Effect of pramlintide on satiety and food intake in obese subjects and subjects with type 2 diabetes
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Self-citationAronne, L., Fujioka, K., Aroda, V., Chen, K., Halseth, A., Kesty, N. C., Burns, C., Lush, C. W., & Weyer, C. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-2003 · Cited by 178
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Cited by
What we talk about when we talk about fat
Rosen, E. D., & Spiegelman, B. M. (2014) · Cell · doi:10.1016/j.cell.2013.12.012 · Cited by 2,373
Leptin and Obesity: Role and clinical implication.
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Adipokines in health and disease
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Anti-obesity drug discovery: advances and challenges
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Metadata
- Authors
- Ravussin, E., Smith, S. R., Mitchell, J. A., Shringarpure, R., Shan, K., Maier, H., Koda, J. E., & Weyer, C.
- Venue
- Obesity
- Publisher
- Wiley
- Published
- 2009-09
- Volume
- 17
- Issue
- 9
- Pages
- 1736-1743
- ISSN
- 1930-7381 (ISSN-L)
- 1930-739X
- OpenAlex
- W1997970568
- Cited by
- 332
- References
- 12
- FWCI
- 22.20
- Type
- journal article
- Language
- en
- Open access
- bronze
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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