Dirlotapide
5-[(4'-trifluoromethyl-biphenyl-2carbonyl)-amino]-1H-indole-2-carboxylic acid benzylmethyl carbamoylamide
Also known as: Slentrol · CP-742,033
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Weight Loss Phase (First 14 days) | 0.01 mL/kg (0.05 mg/kg) | PO | q24h | 14 days | 🌎 NA |
| Weight Loss Phase (Days 15 to 28) | 0.02 mL/kg (0.1 mg/kg) | PO | q24h | 14 days | 🌎 NA |
| Weight Loss Phase (Subsequent Months) | Adjust volume monthly to maintain a target percent weight loss of ≥ 0.7% per week. Max dose: 0.2 mL/kg (0.09 mL/lb) | PO | q24h | Until desired weight is reached | 🌎 NA |
| Weight Management Phase | Adjust dose volume by -50%, 0%, or +50% based on last month's weight loss, then +/- 25% in subsequent months. Max dose: 0.2 mL/kg (0.09 mL/lb) | PO | q24h | 3 months recommended | 🌎 NA |
- Weight Loss Phase (First 14 days): Initial assessment required prior to therapy.
- Weight Loss Phase (Days 15 to 28): Double the initial dose volume.
- Weight Loss Phase (Subsequent Months): If target not met: increase dose by 100% (first adjustment) or 50% (subsequent adjustments). If food consumption is greatly reduced, withhold 1-2 days.
- Weight Management Phase: Establish optimal food intake and physical activity to stabilize body weight.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Dirlotapide is a selective gut microsomal triglyceride transfer protein (GMTP) inhibitor indicated specifically for the management of obesity in dogs. By acting locally in the gastrointestinal tract, it reduces dietary fat absorption and promotes a feeling of satiety, effectively decreasing appetite and begging behaviors.
Clinical Pearl: Dirlotapide requires a highly structured, mathematically driven dosing protocol based on weekly weight loss targets. It is strictly contraindicated in cats due to the high risk of inducing hepatic lipidosis during rapid weight loss.
While the drug is absorbed systemically, its primary efficacy is driven by local action in the gut. Systemic absorption is more closely correlated with adverse effects rather than weight loss efficacy. Successful long-term weight management requires concurrent dietary and lifestyle modifications.
Mechanism of action
Dirlotapide selectively inhibits microsomal triglyceride transfer protein (GMTP) in the enterocytes of the gut.
- Lipid Blockade: Inhibits GMTP → blocks the assembly and release of lipoproteins into systemic circulation → reduces dietary fat absorption.
- Satiety Signaling: The accumulation of lipids within enterocytes triggers the release of Peptide YY (PYY) into the systemic circulation → signals the central nervous system to decrease appetite and induce satiety.
- Action Site: Primarily acts locally in the gut. Systemic blood levels do not directly correlate with efficacy, but rather with systemic toxicity.
Safety & warnings
Contraindications
- Cats (high risk of hepatic lipidosis)
- Dogs with liver disease
- Dogs receiving long-term corticosteroid therapy
- Unmanaged endocrine disease (e.g., hyperadrenocorticism/Cushing's disease)
Adverse effects
- Vomiting (especially during the first month or 3-4 hours post-dose)
- Diarrhea
- Lethargy
- Anorexia
- Salivation
- Constipation
- Dehydration
- Elevated serum hepatic transaminases
Precautions
Important Precautions:
- Species Restriction: Do NOT use in cats. Rapid weight loss in obese cats significantly increases the risk of fatal hepatic lipidosis.
- Endocrine Disease: Pre-existing endocrine diseases (like Cushing's or hypothyroidism) must be managed prior to initiating dirlotapide therapy.
- Duration of Use: Safe use for longer than one year has not been evaluated.
- Reproductive Safety: Safety in breeding, pregnant, or lactating dogs has not been established.
- Hepatic Effects: May cause mild to moderate elevations in serum hepatic transaminases early in treatment.
Drug interactions
Potential altered absorption rate and extent; administer at least 2 hours prior to dirlotapide.
Decreased plasma concentrations during the initial treatment phase; levels typically stabilize and recover during the weight stabilization phase.
Monitoring
- Patient weight (monthly, to guide dose adjustments)
- Adverse gastrointestinal effects (vomiting, diarrhea, anorexia)
- Liver enzymes (baseline and occasional monitoring)
Pharmacokinetics
Half-life
Absorption
Highly variable (22-41%). Presence of food in the gut increases bioavailability.
Distribution
Highly protein bound. Volume of distribution (Vd) is 1.3 L/kg.
Metabolism
Systemically absorbed drug is metabolized in the liver.
Elimination
Excreted primarily in bile (undergoes enterohepatic circulation) and feces. Renal excretion accounts for <1%.
Overdose
Toxicity Profile: Oral doses of 0.5, 1, and 2 mL/kg (2.5X, 5X, and 10X the maximum labeled dose) administered to normal weight Beagles for two weeks were generally tolerated.
Clinical Signs of Overdose:
- Vomiting and diarrhea
- Anorexia and lethargy
- Transient elevations in liver enzymes (transaminases)
Note: No histopathologic evidence of hepatic necrosis was observed at these doses.
Available products
Formulations
- Oral solution
Veterinary
- Dirlotapide Oral Solution 5 mg/mL (Slentrol)
Regulatory status
No regulatory data for: 🇺🇸 US · 🇪🇺 EU · 🇬🇧 UK · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store in the original container at room temperature 15-30°C (59-86°F).
Client information
Important Information for Pet Owners:
- Not a Magic Cure: Dirlotapide helps your dog lose weight by decreasing appetite and reducing fat absorption. However, successful long-term weight management requires permanent changes in diet and exercise.
- Temporary Effect: The decreased appetite is temporary and will fade 1-2 days after stopping the medication. If you do not control food intake after stopping the drug, your dog will regain the weight.
- Side Effects: About 1 in 4 dogs will experience occasional vomiting or diarrhea, usually during the first month or after a dose increase. If vomiting occurs, you can try giving the medication at a different time or with/without food.
- When to Call the Vet: Contact your veterinarian if your dog completely stops eating for more than one day, or if vomiting is severe or lasts longer than 2 days.
- Administration: Use the provided oral dosing syringe. It can be given directly into the mouth or on a small amount of food. Wipe the syringe clean with a dry cloth after use—do not wash it with water.
- Safety Warning: Keep out of reach of children. If accidentally exposed to eyes, flush immediately with clean water.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.