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Cited by 332

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 access
Ravussin, Eric, Smith, Steven R., Mitchell, Julie A., Shringarpure, Reshma, Shan, Kevin, Maier, Holly, Koda, Joy E., Weyer, Christian·2009·Obesity
DOI 10.1038/oby.2009.184
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Abstract

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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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
DOI
10.1038/oby.2009.184
OpenAlex
W1997970568
Cited by
332
References
12
FWCI
22.20
Type
journal article
Language
en
Open access
bronze

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