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Study breakdown

Capromorelin (ENTYCE): The First Ghrelin Receptor Agonist Approved to Stimulate Appetite in Dogs

evidence
The takeaway

Capromorelin, an oral ghrelin receptor agonist, increased food consumption by over 60% and body weight by nearly 6% in healthy dogs over just 4 days, with no significant side effects.

60% more food consumed

Dogs treated with oral capromorelin for 4 days ate over 60% more food than placebo-treated dogs, demonstrating potent appetite stimulation through the ghrelin receptor

What the researchers found

Dogs receiving capromorelin at 3 mg/kg daily showed a mean food consumption increase of 60.55% (±39.87%) compared to a decrease of 11.15% (±14.23%) in placebo dogs (P < 0.001). Body weight increased by a mean of 5.96% (±1.76%) in the treated group versus 0.053% (±1.14%) in controls (P < 0.001).

The drug was well-tolerated across all 12 treated dogs, with no abnormalities on physical examination, serum chemistry, or hematology. The only observed clinical sign was increased salivation in some treated dogs. This demonstrated that activating the ghrelin receptor can dramatically and safely stimulate appetite in dogs.

Why it matters

Loss of appetite is a common and serious problem in sick dogs, contributing to muscle wasting, delayed recovery, and death. Capromorelin represents the first drug specifically designed to address this through a novel mechanism — mimicking the hunger hormone ghrelin. Its success in veterinary medicine has also served as proof of concept for ghrelin receptor agonists more broadly, informing human research into appetite stimulation for conditions like cancer cachexia and age-related wasting.

How the study worked

This was a randomized, masked (blinded), placebo-controlled study in healthy adult Beagle dogs. Twelve dogs (6 males, 6 females) received capromorelin oral solution at 3 mg/kg daily for 4 consecutive days, while 12 matched controls received placebo. Food consumption and body weight were measured throughout. Physical examinations, serum chemistry, and hematology were evaluated before and after treatment to assess safety.

What this study cannot tell us

The study used only healthy dogs, so results may not directly apply to dogs with underlying disease that causes appetite loss. The sample size was small (12 per group) and the treatment duration was only 4 days, leaving long-term efficacy and safety unknown from this study alone. Beagles may not represent all dog breeds. The dramatic food consumption increase in healthy dogs may overestimate effects in clinically ill animals.

How to read the evidence

This is a well-designed randomized, masked, placebo-controlled study, but it was conducted in healthy dogs with a small sample size (n=24) and short duration (4 days). It represents strong preclinical evidence that supported FDA approval of ENTYCE for veterinary use.

When this study was published

Published in 2017, this was a pivotal study supporting the FDA approval of capromorelin (ENTYCE) for appetite stimulation in dogs. It remains the foundational evidence for the first-in-class ghrelin receptor agonist therapeutic.

The bigger picture

Capromorelin is significant beyond veterinary medicine because it was the first ghrelin receptor agonist approved for appetite stimulation in any species. Ghrelin — often called the 'hunger hormone' — is a peptide produced in the stomach that signals the brain to increase appetite and release growth hormone. The success of capromorelin in dogs validated the therapeutic concept of targeting ghrelin receptors to treat appetite loss, a strategy now being explored in humans for cancer cachexia, sarcopenia, and other wasting conditions.

Questions still open

  • Does capromorelin maintain its appetite-stimulating effects over longer treatment periods in dogs with chronic illness?
  • Could the ghrelin receptor agonist approach validated here translate to human appetite stimulation for cancer cachexia or age-related wasting?
  • Does the growth hormone secretagogue activity of capromorelin produce any long-term effects on IGF-1 levels or metabolic parameters in dogs?

Common questions

What is capromorelin and how does it work?
Capromorelin is a drug that mimics ghrelin, the 'hunger hormone' your body naturally produces to signal appetite. It activates the ghrelin receptor in the brain, triggering the same hunger signals that ghrelin would. Sold as ENTYCE for dogs, it's the first ghrelin receptor agonist approved for appetite stimulation in any species — a proof of concept that has implications for human medicine too.
Is there a human version of this appetite-stimulating drug?
Not yet approved, but the concept is being actively studied. Several ghrelin receptor agonists and ghrelin mimetics are in clinical trials for human conditions like cancer cachexia (severe muscle wasting) and age-related appetite loss. The success of capromorelin in dogs helped validate that targeting the ghrelin receptor is a viable approach to treating appetite disorders.

Read the original research

Capromorelin oral solution (ENTYCE®) increases food consumption and body weight when administered for 4 consecutive days to healthy adult Beagle dogs in a randomized, masked, placebo controlled study.

BMC veterinary research, 13(1), 10

Citation

Zollers, Bill; Rhodes, Linda; Heinen, Ernst. (2017). Capromorelin oral solution (ENTYCE®) increases food consumption and body weight when administered for 4 consecutive days to healthy adult Beagle dogs in a randomized, masked, placebo controlled study.. BMC veterinary research, 13(1), 10. https://doi.org/10.1186/s12917-016-0925-z