Determining the effects of combined liraglutide and phentermine on metabolic parameters, blood pressure, and heart rate in lean and obese Male mice

Stephanie E. Simonds, Jack T. Pryor, Frank H. Koegler, Alberte S. Buch-Rasmussen, Lauren E. Kelly, Kevin Grove, Michael A. Cowley

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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 mg/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.

Original languageEnglish (US)
Pages (from-to)683-695
Number of pages13
JournalDiabetes
Volume68
Issue number4
DOIs
StatePublished - Apr 1 2019
Externally publishedYes

Fingerprint

Phentermine
Obese Mice
Heart Rate
Blood Pressure
Weight Loss
Cardiovascular Physiological Phenomena
Body Weight
Pharmaceutical Preparations
Diet
Hyperphagia
Amphetamine
Drug Combinations
Therapeutics
Obesity
Hemodynamics
Liraglutide

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Simonds, S. E., Pryor, J. T., Koegler, F. H., Buch-Rasmussen, A. S., Kelly, L. E., Grove, K., & Cowley, M. A. (2019). Determining the effects of combined liraglutide and phentermine on metabolic parameters, blood pressure, and heart rate in lean and obese Male mice. Diabetes, 68(4), 683-695. https://doi.org/10.2337/db18-1149

Determining the effects of combined liraglutide and phentermine on metabolic parameters, blood pressure, and heart rate in lean and obese Male mice. / Simonds, Stephanie E.; Pryor, Jack T.; Koegler, Frank H.; Buch-Rasmussen, Alberte S.; Kelly, Lauren E.; Grove, Kevin; Cowley, Michael A.

In: Diabetes, Vol. 68, No. 4, 01.04.2019, p. 683-695.

Research output: Contribution to journalArticle

Simonds, SE, Pryor, JT, Koegler, FH, Buch-Rasmussen, AS, Kelly, LE, Grove, K & Cowley, MA 2019, 'Determining the effects of combined liraglutide and phentermine on metabolic parameters, blood pressure, and heart rate in lean and obese Male mice', Diabetes, vol. 68, no. 4, pp. 683-695. https://doi.org/10.2337/db18-1149
Simonds, Stephanie E. ; Pryor, Jack T. ; Koegler, Frank H. ; Buch-Rasmussen, Alberte S. ; Kelly, Lauren E. ; Grove, Kevin ; Cowley, Michael A. / Determining the effects of combined liraglutide and phentermine on metabolic parameters, blood pressure, and heart rate in lean and obese Male mice. In: Diabetes. 2019 ; Vol. 68, No. 4. pp. 683-695.
@article{8e509c77111b475bb3a64378f07d2a6d,
title = "Determining the effects of combined liraglutide and phentermine on metabolic parameters, blood pressure, and heart rate in lean and obese Male mice",
abstract = "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 mg/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.",
author = "Simonds, {Stephanie E.} and Pryor, {Jack T.} and Koegler, {Frank H.} and Buch-Rasmussen, {Alberte S.} and Kelly, {Lauren E.} and Kevin Grove and Cowley, {Michael A.}",
year = "2019",
month = "4",
day = "1",
doi = "10.2337/db18-1149",
language = "English (US)",
volume = "68",
pages = "683--695",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "4",

}

TY - JOUR

T1 - Determining the effects of combined liraglutide and phentermine on metabolic parameters, blood pressure, and heart rate in lean and obese Male mice

AU - Simonds, Stephanie E.

AU - Pryor, Jack T.

AU - Koegler, Frank H.

AU - Buch-Rasmussen, Alberte S.

AU - Kelly, Lauren E.

AU - Grove, Kevin

AU - Cowley, Michael A.

PY - 2019/4/1

Y1 - 2019/4/1

N2 - 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 mg/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.

AB - 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 mg/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.

UR - http://www.scopus.com/inward/record.url?scp=85063611777&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063611777&partnerID=8YFLogxK

U2 - 10.2337/db18-1149

DO - 10.2337/db18-1149

M3 - Article

C2 - 30674622

AN - SCOPUS:85063611777

VL - 68

SP - 683

EP - 695

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 4

ER -