Determining the Effects of Combined Liraglutide and Phentermine on Metabolic Parameters, Blood Pressure, and Heart Rate in Lean and Obese Male Mice.
Stephanie E SimondsJack T PryorFrank H KoeglerAlberte S Buch-RasmussenLauren E KellyKevin L GroveMichael A CowleyPublished in: Diabetes (2019)
Liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, and phentermine, a psychostimulant structurally related to amphetamine, are drugs approved for the treatment of obesity and hyperphagia. There is significant interest in combination use of liraglutide and phentermine for weight loss; however, both drugs have been reported to induce systemic hemodynamic changes, and as such the therapeutic window for this drug combination needs to be determined. To understand their impact on metabolic and cardiovascular physiology, we tested the effects of these drugs alone and in combination for 21 days in lean and obese male mice. The combination of liraglutide and phentermine, at 100 μg/kg/day and 10 mg/kg/day, respectively, produced the largest reduction in body weight in both lean and diet-induced obese (DIO) mice, when compared with both vehicle and monotherapy-treated mice. In lean mice, combination treatment at the aforementioned doses significantly increased heart rate and reduced blood pressure, whereas in DIO mice, combination therapy induced a transient increase in heart rate and decreased blood pressure. These studies demonstrate that in obese mice, the combination of liraglutide and phentermine may reduce body weight but only induce modest improvements in cardiovascular functions. Conversely, in lean mice, the additional weight loss from combination therapy does not improve cardiovascular parameters.
Keyphrases
- heart rate
- blood pressure
- combination therapy
- weight loss
- heart rate variability
- high fat diet induced
- body weight
- bariatric surgery
- metabolic syndrome
- hypertensive patients
- insulin resistance
- type diabetes
- roux en y gastric bypass
- adipose tissue
- bone mineral density
- emergency department
- gastric bypass
- obese patients
- skeletal muscle
- randomized controlled trial
- wild type
- subarachnoid hemorrhage
- body mass index
- open label
- postmenopausal women
- endothelial cells
- blood brain barrier
- high glucose
- smoking cessation
- body composition
- stress induced
- oxidative stress