Capromorelin (Entyce & Elura) for Appetite Stimulation: Evidence and Clinical Use in Dogs and Cats

Bottom line

• Capromorelin is the first FDA-approved oral ghrelin receptor (GHS-R1a) agonist for appetite stimulation, marketed as Entyce for dogs (NADA 141-454) and as Elura for weight loss in cats with chronic kidney disease (CKD; NADA 141-536) [3][4][5].
• In the pivotal canine field study (Zollers et al., JVIM 2016), 244 client-owned inappetent dogs were randomized to capromorelin or placebo; in the 177 evaluable dogs (121 capromorelin, 56 placebo), owner-assessed appetite and food intake at day 3 improved significantly over placebo [1].
• In a 4-day masked, placebo-controlled Beagle study (Zollers et al., BMC Vet Res 2017), capromorelin increased mean food consumption by ~60% and body weight by ~6% versus placebo (P < 0.001) — the pharmacodynamic basis for the label dose [2].
• In cats, a 2025 multicenter RCT (Wofford et al., JFMS) in 176 CKD cats with ≥5% unintended weight loss showed a +6.81% treatment effect on body weight at Day 55 (+5.18% capromorelin vs −1.65% placebo; +0.25 kg; P < 0.0001) [4].
• Mechanism is complementary to mirtazapine and cyproheptadine (distinct neuroendocrine axis), so combination use is pharmacologically rational, though controlled combination-therapy data are lacking [6][7].
• Watch two population-specific cautions: transient hyperglycemia (GH-mediated) in diabetics [8], and a feline-label cardiac precaution (transient HR/BP decrease up to 4 h post-dose) not present on the canine label [5].

Drug facts

• Class: Ghrelin receptor agonist / growth hormone secretagogue (GHS-R1a agonist); synthetic orally bioavailable peptidomimetic.
• Mechanism: Selective agonism at GHS-R1a (a GPCR in hypothalamus, pituitary, and peripheral GI tissue). Activates orexigenic NPY/AgRP neurons in the arcuate nucleus and signals hunger via central and vagal pathways; secondarily drives GH release (and downstream IGF-1), with potential anabolic/lean-mass effects relevant to cachexia [3][6].
• Route/formulation: Oral solution. Entyce (dogs); Elura 20 mg/mL (cats).
• Dose (label): Dogs — 3 mg/kg PO q24h (Entyce). Cats — 2 mg/kg PO q24h (Elura, 20 mg/mL) [4][5].
• Indication: Dogs — stimulation of appetite (Entyce). Cats — management of weight loss in CKD (Elura) [1][4][5].
• Approval: Entyce (dogs) FDA-approved 2016, marketed 2017 (NADA 141-454); Elura (cats) FDA-approved 2021 (NADA 141-536) [3][4][5].
• Label contraindications/precautions: Not for breeding, pregnant, or lactating animals; use with caution with cardiac disease. Feline (Elura) label adds caution in cats with cardiac disease or severe dehydration due to transient HR/BP decreases up to 4 h post-dose [5].
• Common AEs: Dogs — polydipsia/increased urination (transient), loose stools/diarrhea, vomiting, lethargy [1][3]. Cats — vomiting (~30%), hypersalivation, inappetence, behavior change, lethargy [6]; hypersalivation is the most drug-specific AE and occurred exclusively in the capromorelin arm of the pivotal feline RCT [4].

Efficacy — how well does it work?

Dogs (Entyce): field effectiveness and dose-response

The pivotal, prospective, randomized, masked, placebo-controlled field study (Zollers et al., JVIM 2016) enrolled 244 client-owned dogs reported inappetent for at least 2 days. In the 177 dogs evaluable for effectiveness (121 capromorelin, 56 placebo), owners scored appetite at day 0 and day 3; capromorelin produced significantly greater owner-assessed appetite and food-intake improvement than placebo, supporting the conclusion that oral capromorelin is an effective canine appetite stimulant [1].

Laboratory dose-response comes from a 4-day masked, placebo-controlled Beagle study (Zollers et al., BMC Vet Res 2017): as of the published data, capromorelin increased mean food consumption by ~60.6% versus a ~11% decline on placebo, and increased body weight ~6% (≈0.52 kg) versus essentially none on placebo, both P < 0.001 [2].

A note on the "36–58%" figure (contested/derived). The dispatch reviews and several secondary summaries cite a 36–58% food-intake increase attributed to the canine dose-finding data [Rathore 2024 review, 7; and the earlier field-study summaries] — a range that appears to reflect across-dose-group means in the dose-finding program. The primary 4-day Beagle publication verified here reports a single-dose mean increase closer to ~60% versus placebo [2]. Both point to a clinically meaningful orexigenic effect; the exact percentage a clinician quotes should be tied to the specific study and dose group rather than a blanket range. As of July 2026, treat "~36–60% increase in food intake, dose-dependent" as the defensible synthesis.

Cats (Elura): pivotal CKD RCT

The 2025 multicenter, randomized, masked, placebo-controlled RCT (Wofford et al., JFMS) enrolled 176 cats with CKD and ≥5% unintended weight loss. At Day 55, mean body weight rose +5.18% on capromorelin vs −1.65% on placebo, a treatment effect of +6.81% (95% CI 4.21–9.42; ≈+0.25 kg, 95% CI 0.15–0.35; P < 0.0001), with body weight rising progressively across the 55-day period in the treated arm [4]. Supporting field/label data summarized in the 2025 JFMS therapeutics review report that >80% of CKD cats maintained or gained weight on Elura, with a ~5.2% mean 8-week body-weight increase versus loss in controls [6].

Comparators — where does it sit among appetite stimulants?

Capromorelin's orexigenic effect runs through the ghrelin/GHS-R1a axis, which is mechanistically distinct from and complementary to:

• Mirtazapine (α2-adrenergic + 5-HT3 antagonism) [6][7]
• Cyproheptadine (histamine/serotonin antagonism) [7]

Because the pathways differ, capromorelin is additive rather than redundant with these agents, and empiric combination (e.g., capromorelin + transdermal mirtazapine in CKD or cancer-anorexia cats) is used clinically — but no controlled combination-therapy trials exist as of July 2026, so combination benefit remains theoretical [6][7]. Beyond appetite, the ghrelin pathway may add lean-body-mass retention and possible anti-inflammatory effects potentially relevant to sarcopenic CKD cats — a differentiator from mirtazapine [6].

Feline appetite-stimulant positioning (from the 2025 JFMS review) [6]:

Feature	Capromorelin (Elura)	Mirtazapine transdermal (Mirataz)
Route	Oral liquid (20 mg/mL)	Transdermal (pinna)
Dosing	2 mg/kg once daily	2 mg once daily
Primary mechanism	Ghrelin (GHS-R1a) agonist	α2 / 5-HT3 antagonist
Approved indication	CKD weight loss (cats)	Unintended weight loss (cats)
Cardiac caution	Transient HR/BP decrease	Less cardiac concern
Avoid / caution in	Acromegaly; diabetes caution	Liver failure (dose adjust)
GH-mediated muscle benefit	Potential	Not primary mechanism

Safety and adverse effects — what to counsel and monitor

• Dogs (Entyce): Most common AEs are increased water consumption/urination (transient), loose stools/diarrhea, and vomiting; serious adverse events are rare and post-market experience is consistent with the pre-approval profile [1][3][7].
• Cats (Elura): Vomiting (~30%), hypersalivation, inappetence, behavior change, and lethargy [6]. In the pivotal feline RCT, hypersalivation occurred exclusively in the capromorelin arm (P < 0.0001); overall AE rates were otherwise similar between arms (81.4% capromorelin vs 70.7% placebo, P = 0.37) [4]. Counsel owners specifically about hypersalivation.
• Cardiac (cats): The Elura label carries a precaution for cats with cardiac disease (or severe dehydration) because capromorelin causes transient decreases in heart rate and blood pressure up to 4 hours after each dose — clinically relevant in cats with concurrent HCM or other structural cardiac disease [5][6]. This precaution is absent from the canine Entyce label.

Special populations

• Diabetic patients: Capromorelin can transiently raise blood glucose via GH-mediated insulin resistance. A crossover study in 8 healthy dogs (Pascutti et al., Domest Anim Endocrinol 2022) documented transient glycemic elevation from counter-regulatory GH effects [8]. This does not absolutely preclude use, but monitor glucose and insulin requirements; the Rathore 2024 review echoes prudence in diabetics [7]. Feline use in diabetics likewise warrants caution given post-dose hyperglycemia [6].
• Acromegaly / GH-secreting tumors: Avoid — capromorelin stimulates GH secretion and could worsen hypersomatotropism-related insulin resistance and organ changes (explicit contraindication caution in the feline review) [6][7].
• CKD cats (long-term): The Elura program included ~120 cats treated up to 8 weeks plus a 6-month target-animal safety study in healthy DSH cats, with no clinically significant hematologic/biochemical abnormalities in the label dose range [6]. For progressive CKD needing support beyond 8 weeks, the clinical recommendation is to continue indefinitely while monitoring body weight and body condition at each visit, as long as response is maintained and AEs are tolerated; the 2025 review adds no new long-term safety data beyond the label period [6].
• Oncology cachexia / perioperative (dogs, off-label): Increasingly used for cancer-associated cachexia/hyporexia and post-surgical recovery; controlled data in these populations are limited/anecdotal as of July 2026 [7].
• Hypersensitivity: Avoid in animals hypersensitive to the formulation [7].

Multimodal / combination use

Capromorelin + mirtazapine is the most common empiric pairing (orthogonal mechanisms → potential additive appetite effect), used in cats with CKD or cancer anorexia; clinical-trial confirmation is lacking [6][7]. Layer capromorelin onto a broader supportive-care framework — antiemetic control (e.g., maropitant), nausea/uremia management in CKD, and nutritional support — rather than treating it as a standalone fix [6].

Contraindications, precautions & PK

• Contraindications/avoid: breeding/pregnant/lactating animals (canine label); acromegaly / GH-secreting tumors; formulation hypersensitivity [3][6][7].
• Use with caution: cardiac disease (both species; explicit feline precaution with transient HR/BP decrease up to 4 h post-dose) [5][6]; diabetes mellitus (transient hyperglycemia) [6][7]; severe dehydration (feline label) [5].
• PK/PD: orally bioavailable peptidomimetic; selective GHS-R1a agonism drives central + vagal orexigenic signaling and GH release; once-daily dosing reflects the duration of pharmacodynamic effect. Transient hemodynamic (feline) and glycemic effects are time-limited (hours) post-dose [3][5][7]. Consult current formulary/label for species- and indication-specific dosing.

Practical decision support

• Dog, inappetent (any cause): Entyce 3 mg/kg PO q24h is a mechanism-based first-line orexigenic; once-daily oral liquid suits hospitalized and outpatient use [1][3]. Screen for uncontrolled diabetes (monitor glucose) and GH-secreting tumors before starting [7].
• Cat, CKD with ≥5% weight loss: Elura 2 mg/kg PO q24h has the strongest RCT support (+6.81% treatment effect at Day 55) [4]. Before starting, note concurrent cardiac disease (transient HR/BP drop) and counsel owners about hypersalivation [4][5][6].
• Diabetic patient (either species): not an absolute contraindication, but monitor glycemic control and insulin needs during therapy [6][8].
• Refractory anorexia: consider adding mirtazapine (orthogonal mechanism); pair with antiemetic/nausea control and nutritional support [6][7].
• Quote efficacy honestly: cite the specific study/dose (canine ~60% food-intake increase in the Beagle study [2]; feline +6.81% body-weight treatment effect [4]) rather than a generic range.

Frequently Asked Questions

Is capromorelin FDA-approved for cats? Yes. Elura (capromorelin oral solution, 20 mg/mL) is FDA-approved under NADA 141-536 for management of weight loss in cats with CKD, in addition to Entyce for dogs [4][5].

How does capromorelin stimulate appetite? It is a selective ghrelin receptor (GHS-R1a) agonist that activates orexigenic NPY/AgRP neurons in the hypothalamic arcuate nucleus via central and vagal pathways and drives GH release — a neuroendocrine mechanism distinct from mirtazapine and cyproheptadine [3][6].

What does the pivotal feline (Elura) RCT show? In 176 CKD cats with ≥5% unintended weight loss (Wofford et al., JFMS 2025), body weight rose +5.18% on capromorelin vs −1.65% on placebo at Day 55 — a +6.81% treatment effect (≈+0.25 kg; P < 0.0001) [4].

How much does capromorelin increase food intake in dogs? In the 4-day Beagle study, mean food consumption rose ~60% versus placebo (P < 0.001) [2]. Dose-finding summaries cite a broader ~36–58% range across dose groups [7]; quote the figure tied to the specific study and dose.

What is the key safety concern for Elura in cats with heart disease? The Elura label carries a precaution for cats with cardiac disease because capromorelin causes transient decreases in heart rate and blood pressure up to 4 hours after each dose — relevant in cats with concurrent HCM. This precaution is not on the canine Entyce label [5][6].

Can capromorelin be used in diabetic patients? It is not absolutely contraindicated, but it can transiently raise blood glucose via GH-mediated insulin resistance (documented in healthy dogs), so monitor glycemic control and insulin requirements during therapy [6][7].

Can capromorelin be combined with mirtazapine? Yes, empirically — the two act on different pathways, so additive appetite stimulation is plausible and the combination is used in CKD/cancer-anorexia cats. No controlled combination-therapy trials exist as of July 2026 [6][7].

How does Elura differ from Entyce? Both are capromorelin (a ghrelin receptor agonist). Elura is a 20 mg/mL feline formulation dosed 2 mg/kg q24h for CKD-associated weight loss and adds a cardiac precaution; Entyce is the canine appetite-stimulation product dosed 3 mg/kg q24h [4][5].

Changelog

• 2026-07-06: Consolidated the canine hub with three feline/canine dispatch updates into one evergreen hub. Folded in the feline CKD pivotal RCT (Wofford 2025, JFMS), the 2025 JFMS feline therapeutics review (Susi 2025), the 2024 Rathore veterinary review, and the Pascutti 2022 canine glycemic-control study. Corrected citation attributions after source verification: the pivotal field study is Zollers 2016 (JVIM); the 4-day Beagle study is Zollers 2017 (BMC Vet Res); the ghrelin review is Rhodes 2017 (Vet Med Sci). Reconciled the contested canine food-intake figure (verified ~60% in the Beagle study vs the ~36–58% dose-finding range quoted in secondary reviews). Anchored the Elura FDA approval to the DailyMed label (NADA 141-536) after the FDA CVM-update URL failed to resolve.