A novel dual amylin and calcitonin receptor agonist, KBP-089, induces weight loss through a reduction in fat, but not lean mass, while improving food preference

Br J Pharmacol. 2017 Apr;174(7):591-602. doi: 10.1111/bph.13723. Epub 2017 Feb 15.


Background and purpose: Obesity and associated co-morbidities, such as type 2 diabetes and non-alcoholic fatty liver disease, are major health challenges. Hence, there is an important need to develop weight loss therapies with the ability to reduce the co-morbidities.

Experimental approach: The effect of the dual amylin and calcitonin receptor agonist (DACRA), KBP-089, on body weight, glucose homeostasis and fatty acid accumulation in liver and muscle tissue and on food preference was investigated. Furthermore, we elucidated weight-independent effects of KBP-089 using a weight-matched group.

Key results: Rats fed a high-fat diet were treated, s.c., with KBP-089 0.625, 1.25, 2.5 μg·kg-1 or vehicle. KB-089 induced in a dose-dependent and sustained weight loss (~17% by 2.5 μg·kg-1 ). Moreover, KBP-089 reduced fat depot size and reduced lipid accumulation in muscle and liver. In Zucker Diabetic Fatty rats, KBP-089 improved glucose homeostasis through improved insulin action. To obtain a weight-matched group, significantly less food was offered (9% less than in the KBP-089 group). Weight matching led to improved glucose homeostasis by reducing plasma insulin; however, these effect were inferior compared to those of KBP-089. In the food preference test, rats fed a normal diet obtained 74% of their calories from chocolate. KBP-089 reduced total caloric intake and induced a relative increase in chow consumption while drastically reducing chocolate consumption compared with vehicle.

Conclusions and implications: The novel DACRA, KBP-089, induces a sustained weight loss, leading to improved metabolic parameters including food preference, and these are beyond those observed simply by diet-induced weight loss.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects*
  • Adiposity / drug effects*
  • Amylin Receptor Agonists / pharmacology
  • Animals
  • Diet, High-Fat
  • Dose-Response Relationship, Drug
  • Food Preferences / drug effects*
  • Glucose / metabolism
  • Homeostasis / drug effects
  • Male
  • Particle Size
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Zucker
  • Receptors, Calcitonin / agonists*
  • Receptors, Islet Amyloid Polypeptide / metabolism*
  • Structure-Activity Relationship
  • Weight Loss / drug effects*


  • Amylin Receptor Agonists
  • Receptors, Calcitonin
  • Receptors, Islet Amyloid Polypeptide
  • Glucose