Dose combinations of exendin-4 and salmon calcitonin produce additive and synergistic reductions in food intake in nonhuman primates

Am J Physiol Regul Integr Comp Physiol. 2010 Sep;299(3):R945-52. doi: 10.1152/ajpregu.00275.2010. Epub 2010 Jun 16.


Glucagon-like peptide-1 (GLP-1) and amylin mediate the feedback control of eating by seemingly separate, but overlapping mechanisms. This study examined the effects of combined doses of the GLP-1 agonist, exendin-4 (Ex-4), and the amylin analog, salmon calcitonin (sCT), on food intake and meal patterns in adult male rhesus monkeys. Monkeys received intramuscular injections of Ex-4 (0, 0.1, 0.32, or 0.56 microg/kg), sCT (0, 0.1, or 0.32 microg/kg), or combinations thereof before a 6-h daily access to food. Dose combinations produced reductions in food intake that were significantly greater than those produced by the individual doses. Surface plots of the hourly intake indicated a synergistic interaction at lower doses of Ex-4 and sCT during the first 4 h of feeding and additive effects at hours 5 and 6. Meal pattern analysis revealed the combinational doses reduced average meal size and meal frequency by additive interactions, whereas infra-additive effects were apparent at lower doses for first meal size. Combinational doses were further characterized by administration of repeated daily injections of 0.56 microg/kg Ex-4 + 0.32 microg/kg sCT for 5 days. This resulted in sustained reductions in daily food intake (>70% from saline baseline) for 5 days with residual reductions ( approximately 48% from saline baseline) persisting on day 1 following the injections. In contrast, when pair-fed an identical amount of daily food, there was a compensatory food intake increase on day 1 following the pair-feeding ( approximately 132% of saline baseline). Such data suggest Ex-4 and sCT interact in an overall additive fashion to reduce food intake and further the understanding of how GLP-1 and amylin agonist combinations influence feeding behavior.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Calcitonin / administration & dosage
  • Calcitonin / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Synergism
  • Drug Therapy, Combination
  • Eating / drug effects*
  • Exenatide
  • Feeding Behavior / drug effects
  • Macaca mulatta
  • Male
  • Peptides / administration & dosage
  • Peptides / pharmacology*
  • Venoms / administration & dosage
  • Venoms / pharmacology*


  • Peptides
  • Venoms
  • salmon calcitonin
  • Calcitonin
  • Exenatide