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Enhanced Weight Loss With Pramlintide/Metreleptin: An Integrated Neurohormonal Approach to Obesity Pharmacotherapy.
- Source :
- Obesity (19307381); Sep2009, Vol. 17 Issue 9, p1736-1743, 8p, 1 Diagram, 4 Charts, 2 Graphs
- Publication Year :
- 2009
-
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<superscript>2</superscript>; 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- WEIGHT loss
DRUG efficacy
OBESITY treatment
DRUG therapy
DIET therapy
Subjects
Details
- Language :
- English
- ISSN :
- 19307381
- Volume :
- 17
- Issue :
- 9
- Database :
- Complementary Index
- Journal :
- Obesity (19307381)
- Publication Type :
- Academic Journal
- Accession number :
- 43986074
- Full Text :
- https://doi.org/10.1038/oby.2009.184