Metformin
Metformin hydrochloride; Dimethylbiguanide HCl
Also known as: Glucophage XR · Glumetza · Fortamet · Riomet · Dimethylbiguanide HCl · Metforimini hydrochloridium
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
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Non-insulin dependent diabetes mellitus (NIDDM) | 50 mg (total dose) per cat PO twice daily | PO | q12h | — | 🌎 NA |
| Early NIDDM | 2 mg/kg PO q12h | PO | q12h | — | 🌎 NA |
| General Use Warning | Not recommended | PO | — | — | 🌎 NA |
- Non-insulin dependent diabetes mellitus (NIDDM): May be efficacious only in cats with detectable concentrations of insulin at time of treatment.
- General Use Warning: Author states 'metformin has been shown toxic to cats and should not be used. It is also ineffective.'
Birds
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| General | 100-500 mg/L of drinking water | PO | Continuous | — | 🌎 NA |
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Metformin is a biguanide oral antihyperglycemic agent widely used in human medicine for the management of type 2 diabetes. In veterinary medicine, its use is highly controversial and generally considered to have limited efficacy.
- Cats: Investigated as an adjunctive treatment for non-insulin-dependent diabetes mellitus (NIDDM). However, clinical success is very limited, and the drug is often poorly tolerated due to gastrointestinal toxicity. Some veterinary endocrinologists strongly advise against its use in felines.
- Horses: Researched for the management of Equine Metabolic Syndrome (EMS) and insulin dysregulation. Unfortunately, metformin has a highly unfavorable pharmacokinetic profile in horses, characterized by extremely low oral bioavailability (~4-7%) and a very rapid elimination half-life, making systemic efficacy questionable.
Clinical Pearl: Unlike sulfonylureas (e.g., glipizide) or insulin, metformin does not stimulate pancreatic insulin release and therefore rarely causes hypoglycemia when used as a sole agent.
Mechanism of action
Metformin acts primarily as an insulin sensitizer and inhibitor of hepatic glucose output. Its actions are multifaceted:
- AMPK Activation: Metformin activates AMP-activated protein kinase (AMPK) in hepatocytes → decreases hepatic gluconeogenesis (glucose production).
- Peripheral Sensitization: Increases insulin's ability to transport glucose across cell membranes in skeletal muscle → increases peripheral glucose uptake.
- Intestinal Absorption: May decrease the intestinal absorption of dietary glucose.
- Advanced Glycosylation: Inhibits the formation of advanced glycosylation end-products.
Because it does not stimulate insulin production or release from pancreatic beta cells, it does not directly induce hypoglycemia.
Safety & warnings
Contraindications
- Hypersensitivity to metformin
- Renal dysfunction
- Metabolic acidosis
- Concurrent use of parenteral iodinated contrast agents (temporary contraindication)
Adverse effects
- Lethargy
- Inappetence
- Vomiting
- Diarrhea
- Weight loss
- Lactic acidosis (rare but severe)
Precautions
Important Precautions:
- Renal Impairment: Metformin is primarily excreted unchanged by the kidneys. Accumulation can lead to severe lactic acidosis in patients with renal dysfunction.
- Gastrointestinal Toxicity: Has a narrow margin of safety regarding GI upset in small animals.
- Lactation: Excreted in maternal milk in levels equivalent to plasma. Use with caution in lactating queens.
- Dosing Challenges: Human dosage forms (e.g., 500 mg tablets) may be difficult to accurately dose in cats, increasing the risk of toxicity.
Drug interactions
May increase risk for hypoglycemia
Can cause a 60% increase in peak metformin plasma levels and a 40% increase in AUC
May reduce hypoglycemic efficacy
May reduce hypoglycemic efficacy
Can increase the AUC and plasma levels of metformin by 22%; metformin can decrease the peak plasma concentrations and AUC of furosemide
May cause acute renal failure and lactic acidosis if used within 48 hours of a metformin dose
May reduce hypoglycemic efficacy
May reduce hypoglycemic efficacy
Monitoring
- Fasting blood glucose
- Appetite and attitude
- Body condition
- PU/PD resolution
- Serum fructosamine and/or glycosylated hemoglobin levels
- Renal function (baseline and annually)
- Adverse effects (especially GI signs)
Pharmacokinetics
Half-life
Absorption
Cats: Variably absorbed after oral administration (35-67%). Horses: Very low oral bioavailability (4% fed, 7% fasted).
Distribution
Cats: Steady-state volume of distribution is 0.55 L/kg.
Metabolism
Not extensively metabolized.
Elimination
Primarily eliminated via the kidneys. Cats: Total clearance is 0.15 L/hr/kg.
Overdose
Overdose & Toxicity Profile:
- Small Animals: Hypoglycemia is not commonly seen in overdoses of metformin alone. However, the drug has a narrow margin of safety regarding gastrointestinal upset.
- Clinical Signs: Vomiting and diarrhea are the most common findings in dogs and cats following accidental ingestion.
- Human Data: Massive overdoses (e.g., 100 grams) caused hypoglycemia only 10% of the time, but lactic acidosis occurred. Lactic acidosis has been seen in human overdoses of 7 to 20 grams. It is unknown at what exact dose acidosis may occur in domestic animals.
Management: Treatment is largely supportive and symptomatic, focusing on managing GI distress and monitoring acid-base status and renal function.
Available products
Formulations
- Extended-Release Oral Tablets
- Oral Solution
Human-labeled
- Metformin HCl Oral Tablets: 500 mg, 850 mg & 1000 mg (Glucophage, generic)
- Metformin HCl Extended-Release Oral Tablets: 500 mg, 750 mg & 1000 mg (Glucophage XR, Glumetza, Fortamet, generic)
- Metformin HCl Oral Solution: 500 mg/5 mL (Riomet)
Regulatory status
No regulatory data for: 🇺🇸 US · 🇪🇺 EU · 🇬🇧 UK · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store protected from light at a controlled room temperature of 20-25°C (68-77°F), with excursions permitted to 15-30°C (59-86°F).
Client information
Guidance for Pet Owners:
- Investigational Use: Understand that the use of metformin in cats is highly 'investigational' and off-label. Its effectiveness in veterinary medicine is still debated.
- Side Effects: Watch closely for signs of stomach upset, including vomiting, diarrhea, loss of appetite, or extreme lethargy.
- Reporting: Report any untoward effects or changes in your pet's behavior to your veterinarian immediately.
- Administration: Do not crush or break extended-release tablets unless specifically instructed by your veterinarian. Ensure fresh water is always available.
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.